January 11, 2018 | Author: Anonymous | Category: N/A
Financial Highlights Boehringer Ingelheim group of companies 2008
2007
change
11,595
10,952
6 %
Europe
33 %
33 %
Americas
48 %
50 %
Asia, Australasia, Africa
19 %
17 %
96 %
96 %
4 %
4 %
Research and development
2,109
1,900
11 %
Personnel costs
3,004
2,886
4 %
41,300
39,800
4 %
Operating income
1,980
2,100
- 6 %
Operating income as % of sales
17.1%
19.2 %
Amounts in millions of EUR, unless otherwise indicated
Net sales by region
by business
Human Pharmaceuticals
Boehringer Ingelheim
Animal Health
Annual Report 2008
Income after taxes
Annual Report 2008
www.boehringer-ingelheim.com
Average number of employees
1,428
1,812
12.3 %
16.5 %
4,703
3,372
42.2 %
35.0 %
1,997
2,392
-17 %
Investments in tangible assets
665
654
2 %
Depreciation of tangible assets
453
432
5 %
Income after taxes as % of sales Shareholders’ equity Return on shareholders’ equity Cash flow
-21 %
39 %
Value through Innovation Value through Innovation Top 5 products — Prescription Medicines
30234/03/09
Net sales 2008
nopq
Top 5 products — Consumer Health Care
in millions of EUR
change
Net sales 2008
in millions of EUR
change
spiriva®
2,070
+16 %
micardis®
1,219
+15 %
dulcolax®
134
+7 %
mucosolvan®
125
+7 %
flomax®/alna®
pharmaton®
1,075
+5 %
115
+21 %
mirapex®/sifrol®
752
+17 %
buscopan®
99
+24 %
combivent®
553
-15 %
zantac®
92
-17 %
Financial Highlights Boehringer Ingelheim group of companies 2008
2007
change
11,595
10,952
6 %
Europe
33 %
33 %
Americas
48 %
50 %
Asia, Australasia, Africa
19 %
17 %
96 %
96 %
4 %
4 %
Research and development
2,109
1,900
11 %
Personnel costs
3,004
2,886
4 %
41,300
39,800
4 %
Operating income
1,980
2,100
- 6 %
Operating income as % of sales
17.1%
19.2 %
Amounts in millions of EUR, unless otherwise indicated
Net sales by region
by business
Human Pharmaceuticals
Boehringer Ingelheim
Animal Health
Annual Report 2008
Income after taxes
Annual Report 2008
www.boehringer-ingelheim.com
Average number of employees
1,428
1,812
12.3 %
16.5 %
4,703
3,372
42.2 %
35.0 %
1,997
2,392
-17 %
Investments in tangible assets
665
654
2 %
Depreciation of tangible assets
453
432
5 %
Income after taxes as % of sales Shareholders’ equity Return on shareholders’ equity Cash flow
-21 %
39 %
Value through Innovation Value through Innovation Top 5 products — Prescription Medicines
30234/03/09
Net sales 2008
nopq
Top 5 products — Consumer Health Care
in millions of EUR
change
Net sales 2008
in millions of EUR
change
spiriva®
2,070
+16 %
micardis®
1,219
+15 %
dulcolax®
134
+7 %
mucosolvan®
125
+7 %
flomax®/alna®
pharmaton®
1,075
+5 %
115
+21 %
mirapex®/sifrol®
752
+17 %
buscopan®
99
+24 %
combivent®
553
-15 %
zantac®
92
-17 %
Contents 2 The shareholders’ perspective 4 Key aspects 2008 8 Corporate bodies
Corporate Responsibility The ethical principles that guide our company have created a culture of corporate responsibility and commitment. page 28
10 Group Management Report
Comparison of balance sheets/ financial data 1999—2008 (in millions of EUR)
30 Corporate Responsibility 30 Caring for our neighbours – “We care” 32 Environmental protection and occupational safety
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
400
344
322
302
242
267
233
554
547
539
1,992
2,217
2,467
2,840
2,767
2,712
2,900
2,886
2,972
3,177
849
1,135
1,008
1,689
2,462
2,756
3,396
3,043
1,638
1,739
3,241
3,696
3,797
4,831
5,471
5,735
6,529
6,483
5,157
5,455
944
1,021
1,014
971
1,000
1,085
1,229
1,280
1,387
1,561
1,870
1,938
2,314
2,360
2,537
2,477
3,013
3,137
2,912
3,496
459
477
1,002
1,055
1,134
1,333
1,247
945
1,015
1,312
Current assets
3,273
3,436
4,330
4,386
4,671
4,895
5,489
5,362
5,314
6,369
Total assets
6,514
7,132
8,127
9,217
10,142
10,630
12,018
11,845
10,471
11,824
Liabilities and equity (as of 31.12.)
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
Financial assets Fixed assets Inventories Accounts receivable (incl. deferred charges and deferred taxes)
Our own research and development continues to be the major driver of innovative, new medicines. page 44
30 Caring for patients – The viramune® Donation Programme
Intangible assets Tangible assets
Research & Development
Corporate Responsibility
Assets (as of 31.12.)
Cash and cash equivalents (incl. securities)
39 Our people Research & Development 46 Our R&D strategy 48 Our R&D sites 51 Non-clinical research and development 53 From test tube to bioreactor – A seamless path for biopharmaceuticals 53 Clinical development 56 2008 – The year of landmark trials 58 Bridge to academia
Human Pharmaceuticals
Shareholders’ capital
332
211
200
178
178
178
178
178
178
178
1,982
2,362
2,753
2,818
3,139
3,297
2,940
3,275
1,385
3,101
Net income
320
379
401
537
529
888
1,491
1,722
1,809
1,424
Total equity
2,634
2,952
3,354
3,533
3,846
4,363
4,609
5,175
3,372
4,703
0
0
1
203
188
193
216
188
167
190
Group equity
2,634
2,952
3,355
3,736
4,034
4,556
4,825
5,363
3,539
4,893
Provisions (incl. deferred taxes)
2,631
2,932
3,150
3,568
3,963
4,172
4,958
4,641
4,726
5,120
Reserves (incl. currency conversion difference)
We are committed to the goal of serving humankind through new drugs and therapies. page 62
Minority interests
60 Our business Human Pharmaceuticals 64 Highlights Branded Prescription Medicines* 67 Highlights Generic Prescription Medicines 68 Highlights Consumer Health Care
Liabilities (incl. deferred charges)
1,249
1,248
1,622
1,913
2,145
1,902
2,235
1,841
2,206
1,811
Total liabilities
3,880
4,180
4,772
5,481
6,108
6,074
7,193
6,482
6,932
6,931
Total liabilities and equity
6,514
7,132
8,127
9,217
10,142
10,630
12,018
11,845
10,471
11,824
Product Supply and Industrial Customer 74 Biopharmaceuticals
Product supply and Industrial Customer
76 Pharmaceuticals Production 78 Pharma Chemicals 79 Manufacturing excellence in our centre for global animal health vaccines Animal Health 81 Highlights Animal Health 84 Samples of the product portfolio 106 Consolidated Financial Statements 2008 108 Overview of the major consolidated companies 110 Consolidated balance sheet
Animal Health With innovative veterinary medicines that accommodate the needs of both man and animal, we are a reliable partner for animal owners and veterinarians. page 80
We produce drugs for our own Human Pharmaceuticals business in a globally coordinated production network. Furthermore we offer customised manufacturing services to our industrial customers. page 70
Summary of selected financial data
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
Net sales
5,086
6,188
6,694
7,580
7,382
8,157
9,535
10,574
10,952
11,595
Operating income
655
800
980
1,082
901
1,372
1,923
2,140
2,100
1,980
Operating income as % of net sales
12.9
12.9
14.6
14.3
12.2
16.8
20.2
20.2
19.2
17.1
Income after taxes
320
379
401
551
537
908
1,514
1,729
1,812
1,428
Income after taxes as % of net sales
6.3
6.1
6.0
7.3
7.3
11.1
15.9
16.4
16.5
12.3
Return on shareholders’ equity (in %)
13.8
14.4
13.6
16.0
15.0
23.1
34.2
37.4
35.0
42.2
Equity ratio (in %)
40.4
41.4
41.3
38.3
37.9
41.0
38.4
43.7
32.2
39.8
Cash flow
111 Consolidated profit and loss statement
737
791
1,117
1,049
1,059
1,430
2,069
2,317
2,392
1,997
Financial funds
1,055
1,094
1,645
2,645
3,516
4,015
4,585
3,934
2,581
2,932
Personnel costs
1,527
1,749
1,916
2,175
2,252
2,443
2,671
2,836
2,886
3,004
30.5
29.9
28.0
26.8
26.4
25.9
34,221 35,529
37,406
38,428
39,800
41,300
112 Cash flow statement
Personnel costs as % of net sales
113 Statement of changes in group equity
Average number of employees
114 Notes to the consolidated financial statements
Research and development costs*
132 Auditor’s Report
R&D as % of net sales
Flap Comparison of balance sheets / financial data 1999–2008
* The patient reports are authentic reports which refer to personal experience only. Please note that other patients may experience different treatment results. Individual treatment regimes have always to be discussed between patient and physician case by case.
28.3
28.6
28.7
27,325
27,980
31,843
826
968
1,019
1,304
1,176
1,232
1,360
1,574
1,900
2,109
16.2
15.6
15.2
17.2
15.9
15.1
14.3
14.9
17.3
18.2
Investments in tangible assets
377
497
548
634
516
427
532
596
654
665
Depreciation of tangible assets
256
288
305
340
354
377
439
419
432
453
* As��������������������������������������� of the year 2008, costs for phase IV clinical ���������������� trials are included in R&D costs, among other expenses. The 2007 figure was adjusted accordingly. please turn over
30.0 26,448
Our core principles – Leitbild shareholders’ perspective Boehringer Ingelheim has been a successful, familyowned business for more than 100 years and intends to remain so for the second century of its existence. Although it is impossible to predict the future precisely, we are actively and creatively facing the changing tasks and challenges, building on our experiences and achievements. This gives us the strength, direction and confidence to shape our future. We have committed ourselves to the goal of serving humankind through research into diseases and the development of new drugs and therapies. In this endeavour the future of our company will depend on its innovative capability. In all our activities we safeguard our employees, facilities and the environment from harmful influences, conserve natural resources and promote environmental awareness. Parallel to pursuing these goals we seek to foster economic and social well-being in the countries and communities where we do business. In order to realise our goals, we must be financially successful, be willing to make the necessary changes, and be critically receptive to new ideas and developments. Maintaining and improving the performance of the company take precedence over maximising earnings in the short term.
The shareholders’ perspective
We, the shareholders of Boehringer Ingelheim, regard ourselves as being actively engaged in the corporation and its future development as an independent, family-owned company. And we have the goal that drives us: we want to serve humankind through research into diseases and the development of new drugs and therapies. The future of our company thus depends directly on its innovative capability. Our employees are the guarantors of this capability and our most important corporate asset. They form the core of our unique corporate culture as a family-owned company, which we wish to preserve. Continual and sustained further development of our company offers the potential for Boehringer Ingelheim to secure and extend our position as a global, independent company with a business model based on organic growth. Its basis will be established, on the one hand, by a strong pipeline of innovative products from our own research and development and, on the other hand, by selling the products successfully in a market characterised by intense competition. We shareholders have provided both the financial means and a stable strategic framework for this continuous growth and sustainable alignment of the company. And, as shareholders, we note with appreciation and satisfaction that our company has also realised our ambitious goals and expectations for 2008. Given our long personal cooperation, it is a matter of importance to us to express our special gratitude to the members of the Board of Managing Directors, who were in charge until the end of 2008. They hand on a successful company that is well-equipped for the future. The good results of the past are both motivation and mission for the fourth generation of shareholders. We regard ourselves as stewards of sustainable success. Safeguarding the sustainability of our company is also a challenge we face, and the company must assert itself in an increasingly volatile business environment. Last year, 2008, stands for the start of a period in which the general business environment is undergoing significant change. The internal preconditions exist to continue our successful growth in the years ahead. However, for us too, the impact of the financial crisis and the consequent economic crisis cannot be assessed.
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Christian Boehringer
In the medium-term future, a challenge confronting our company will arise from the expiry of patent protection for several drugs, which will have a negative impact on our revenues. At the same time, however, we are justifiably confident of being in the favourable position to bring new and innovative drugs to the market. However, the investment necessary for this will also reduce our earnings. And with weakening growth rates and increased cost control over healthcare budgets in the traditionally most important pharmaceutical markets, we must concentrate more on the growing markets and their specific requirements. This prospect represents the basis of a new chapter in Boehringer Ingelheim’s company history that we will now open with the Board of Managing Directors. As shareholders, we wish to look ahead together with the members of the Board of Managing Directors and, appreciative of the current success, to identify future challenges and jointly commit to continually developing our way of working and our business model in order to remain sustainable. At the same time, we are determined to preserve our company’s fundamental values.
Christian Boehringer Chairman of the Shareholders’ Committee
The shareholders’ perspective
Key aspects 2008
2008 was again a successful year for Boehringer Ingelheim. Despite the changing global pharmaceutical market and the crisis of the international financial system, we continued to stay on a growth path. The success of Boehringer Ingelheim as an independent and dynamically growing pharmaceutical company was maintained, and in 2008 we also grew above average and outpaced the world market for the ninth consecutive year. And of greatest importance is that our innovative medicines help millions of patients. As in previous years, in 2008 we also advanced our projects in late stage clinical development with continuously increasing investments in research and development and thereby securing our future. Our business results Our corporation-wide net sales in 2008 amounted to EUR 11,595 million. In local currency terms, we posted growth of 9.5 %. In euro terms, growth was 5.9 %. In our prime business area, Human Pharmaceuticals, Prescription Medicines’ sales rose by 9.1 % in local currency terms to EUR 11,128 million (5.5 % in euro terms). We are one of the fastest growing pharmaceutical companies worldwide. We have achieved a 2 % share (according to the IMS Health database) of the world market, thereby further consolidating our position among the leading international pharmaceutical companies. As foreseen, our R&D expenditure increased disproportionately in 2008 (+11% compared to the previous year). Hence, our operating income of EUR 1,980 million decreased by – 5.7 % compared to the previous year. This corresponds to a return on sales of 17.1 %. We are pleased that all our core products achieved good growth in 2008 and once again improved their market position.
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Wolfram Carius, Andreas Barner, Engelbert Tjeenk Willink, Hubertus von Baumbach (from left to right)
Our blockbuster products each with net sales of more than USD 1 billion, spiriva®, micardis®, flomax®/alna® and mirapex®/sifrol®, together posted net sales of more than EUR 5 billion, resulting in average growth of more than 10 % compared to the previous year. Our self-medication business segment Consumer Health Care (CHC) also developed positively in 2008, with growth of 5.4 % in local currencies (4.3 % in euro terms) to EUR 1,190 million. This business contributed 10.3 % to the company’s net sales. Our business segment Industrial Customer posted gratifying growth (12.3 % in local currencies, 10.8 % in euro terms), with net sales of EUR 819 million, and contributed 7 % to the company’s net sales. Biopharmaceuticals contributed the biggest share, with net sales increasing by 22.8 % to EUR 569 million. Boehringer Ingelheim is a leading company in the development and manufacture of biopharmaceuticals. Besides Human Pharmaceuticals, our important business area, Animal Health, posted extraordinary growth in net sales of 19.5 % in local currencies (14.4 % in euro terms) to EUR 467 million, making Boehringer Ingelheim one of the fastest growing animal health companies. Our landmark trials In 2008, Boehringer Ingelheim published the results of the landmark trials ontarget™, profess®, transcend®, uplift® and ecass 3™. We have provided evidence-based answers to some of the most challenging questions in medicine today. Our trials will improve medical knowledge and management of three common causes of death: heart disease, stroke and chronic obstructive pulmonary disease (COPD). These currently claim the lives of over 20 million people each year and will be the three leading causes of death by 2020.
Key aspects 2008
People are key We are proud of our employees and very grateful for their achievements. The work climate in our company is very good, and the attractiveness of Boehringer Ingelheim as an employer of choice is widely acknowledged and was again confirmed last year in highly regarded, independent surveys. In 2008, we succeeded for the seventh consecutive year in coming first in the VAA (Verband angestellter Akademiker und leitender Angestellter in der Chemischen Industrie) most preferred employer survey of executives in the German chemical and pharmaceutical industries. Value through Innovation – our late stage development compounds We conduct research and develop innovative medicines and therapies for the benefit of patients. Our compounds in late stage clinical development made good progress in 2008, giving us the confidence that we will soon be able to launch further new compounds from our own research and development on the market. In our pipeline in the area of metabolism we have convincing oral anti-diabetic compounds, establishing the company in the field of medications for the treatment of type 2 diabetes. Our oncology pipeline has also developed favourably and, with four compounds in development, is well-filled. New product launches In 2008, Boehringer Ingelheim was granted marketing authorisation for pradaxa® in the indication prevention of venous thrombo-embolic events in adults who have undergone total hip or knee replacement surgery. We continue to evaluate the efficacy and safety of pradaxa® in a range of thrombo-embolic disease conditions, including stroke prevention in patients with atrial fibrillation (SPAF), in the treatment of acute venous thrombo-embolism (VTE), the secondary prevention of venous thrombo-embolism and prevention of cardiac events in patients with acute coronary syndrome (ACS).
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Outlook and commitment We, the members of the Board of Managing Directors, together with all of the corporation’s employees, want to reinforce the future viability of Boehringer Ingelheim in order to master the challenges that will arise for the company. As anticipated, our earnings will in the medium-term be burdened by patent expiries. At the same time, we will make investments for preparing the launch of our new compounds, which will secure the long-term growth of the company. Furthermore, we expect significant changes and increased volatility in the general business environment and we will continuously monitor and actively counteract their potential impact on the company. Our goal is to successfully position the company in a dynamic and changing business environment in order to continue to offer patients the best possible medications for treating their conditions.
Andreas Barner
Hubertus von Baumbach
Wolfram Carius
Engelbert Tjeenk Willink
Key aspects 2008
Corporate bodies
Shareholders’ Committee
Board of Managing Directors (until 31.12.2008)
Christian Boehringer Chairman of the Shareholders’ Committee
Dr Alessandro Banchi Chairman of the Board
Albert Boehringer
Corporate Board Division Chairman of the Board Corporate Board Division Pharma Marketing
Christoph Boehringer
and Sales
Erich von Baumbach Jr.
Prof.* Dr Dr Andreas Barner Vice-Chairman of the Board
Ferdinand von Baumbach
Corporate Board Division Pharma Research, Development and Medicine
Dr Mathias Boehringer Dr Hans-Jürgen Leuchs Corporate Board Division Operations
Advisory Board
Corporate Board Division Animal Health
Prof. Dr Michael Hoffmann-Becking
Prof. Dr Marbod Muff
Attorney at Law, Düsseldorf
Corporate Board Division Finance
Chairman of the Advisory Board
Corporate Board Division Human Resources
Egbert Appel Trustee, Martin Hilti Family Trust;
Board of Managing Directors
Member of the Board and
(from 01.01.2009)
Managing Director, Hilti Foundation (from 01.01.2009)
Prof.* Dr Dr Andreas Barner Chairman of the Board
Dr Rolf-E. Breuer
Corporate Board Division Chairman of the Board
Frankfurt (Main)
and Pharma Research, Development and Medicine
(until 31.12.2008) Hubertus von Baumbach Dr Andreas Kreimeyer
Corporate Board Division Finance and
Member of the Board of
Animal Health
Executive Directors and Research Executive Director BASF SE
Prof. h. c. Dr Wolfram Carius
(from 01.08.2008)
Corporate Board Division Human Resources and Operations
Prof. Dr Fredmund Malik Chairman of the Board
Engelbert Tjeenk Willink
Malik Management Zentrum St. Gallen AG
Corporate Board Division Marketing and Sales Human Pharma * Republic of Austria
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Our corporate vision – “Value through Innovation”
The objectives and beliefs of Boehringer Ingelheim can be summed up in a single phrase: Value through Innovation. This vision has helped us to build on our strengths and make the most of our distinctive character. In a competitive and fast-changing world, the value of products, services and companies is constantly changing. Real customer value today can only be created by constantly developing new solutions and doing what we already do better.
Our company
We are a research-driven company dedicated to research ing and developing, manufacturing and marketing pharmaceuticals that improve health and quality of life. Our business areas consist of Human Pharmaceuticals and Animal Health. We have 41,300 employees in 138 affiliated companies worldwide, research and development (R&D) facilities in ten countries and production plants in 16 countries. R&D expenditure in Prescription Medicines corresponds to more than 22% of net sales in this segment. Our headquarters is at Ingelheim, the German town where the family-owned company was founded in 1885.
Group Management Report
Business and operating environment
for industrial countries. The situation on the financial markets has worsened severely. At the same time, there has been a noticeable reduction in worldwide consumer prices since the middle
Overview
of the year. Raw material prices, which had pre-
The economic environment deteriorated signifi-
viously caused the steep rise in inflation, fell
cantly in 2008. The problems on the US mort-
sharply as demand was decreased because of the
gage market that were already indicated in the
economy. On the foreign exchange market, the
year before, have since developed into a world-
US dollar reached an historic low against the
wide financial crisis. The expansion phase of the
euro in mid-2008, but stabilised at a much
worldwide economy ceased toward the end of
higher level at the end of the year. The Japanese
the third quarter of 2008 and was replaced by
yen also increased in value significantly against
an unusually sharp downward trend.
the euro. At the end of 2008, the exchange rate
After the worldwide economy grew by 3.7 % in
2002.
of the euro to the yen was at its lowest level since 2007, current estimates for 2008 are for growth of only 2.5 %. Forecasts for 2009 predict that the
In Germany, the economic momentum slowed
economic situation will be further aggravated;
down considerably from the middle of the year
negative growth has already been predicted
onwards as a result of the turbulences on the
Net Netsales salesbybybusinesses businesses2008 2008 (in(in millions millions ofEUR) EUR) Net sales byof business
Net Netsales salesbybyregion region2008 2008
(in(inmillions EUR) millions EUR) Net sales by regionofof
(in millions of EUR)
(in millions of EUR)
Medicines Prescription Medicines Prescription 8,660 8,660 Care Health Consumer Care Health Consumer 1,141 1,141
9,111 9,111
5,560 5,560
Europe Europe 3,578 3,578
3,877 3,877
1,190 1,190
Biopharmaceuticals Biopharmaceuticals 463 463
569 569
and Chemicals Pharma and Chemicals Pharma Production Pharmaceuticals Production Pharmaceuticals 276 276
250 250
Health Animal Health Animal 408 408
467 467
07070808
10
Americas Americas 5,463 5,463
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Total Total
Africa Australasia, Asia, Africa Australasia, Asia, 1,911 1,911
10,952 10,952
2,158 2,158
07070808
11,595 11,595
worldwide financial markets. The gross domestic
industry. So far, no extraordinary risks to our
product, adjusted for price, grew by only 1.3 %
company have been identified. In this situation,
compared with the previous year, which was
we anticipate changes in the pharmaceutical in-
well below the level of growth for 2007 (2.5 %).
dustry, but no short-term intervention, owing to
The number of unemployed people dropped to
the complex legislative procedures.
an average of 3.3 million for the year and is thus still strongly marked by the positive devel-
The group sales of Boehringer Ingelheim totalled
opments in the first three quarters. Develop-
EUR 11,595 million (+5.9 %) in the reporting
ments at the end of the year have already shown,
period. Unfavourable developments in exchange
however, that the economic slowdown will also
rates compared with the previous year placed a
become more apparent on the German employ-
burden of approximately EUR 365 million on
ment market.
the group sales. With adjustments for these negative exchange rate effects, worldwide sales of
In a market environment shaped by the turbu-
almost EUR 12 billion would have been achieved.
lences on the international financial markets,
This means that, on the worldwide pharmaceu-
worldwide pharmaceutical activities recorded
tical market, we achieved stronger growth than
growth in sales. Growth rates for the worldwide
the market for the ninth consecutive year. We
pharmaceutical market, adjusted for currency
were pleased that demand for our products
effects, fell again, however, according to the
remained high, particularly in view of the finan-
latest market data from market research insti-
cial crisis.
tutes for the last financial year. The reasons for this development are partly the state regulation
Growth in the group of companies was once
of pharmaceutical activities and partly the
again supported by all three regions. The highest
expiry of patent rights for some products. Like
percentage of growth was recorded in the
all other pharmaceutical companies, Boehringer
region Asia, Australasia and Africa (AAA), with
Ingelheim is also affected by this. Cost pressure
an increase in sales of around 13 %. Europe saw
on health systems leads to increased prescrip-
virtually identical growth to 2007 (+8.4 %),
tion of generic drugs and tighter regulation of
while sales in the Americas region were only
the price of medicines. In addition, the patent
slightly higher than in the previous year (+1.8 %).
rights of profitable products are being attacked
The negative impact of the currency effects
increasingly early. The considerably lower prices
mentioned above was felt strongly here.
of generic products that are subsequently produced impede the capital-intensive development of innovative medicines. Despite these changes
Net sales by region (in millions of EUR)
2008
2007
in overall conditions, Boehringer Ingelheim
Americas
5,560
5,463
will remain committed to research into new and
Europe
3,877
3,578
innovative pharmaceuticals.
Asia, Australasia, Africa
2,158
1,911
At present, there are only limited signs of the
Business with Prescription Medicines accounts
effects that the turbulences on the international
for around 79 % of group sales at Boehringer
financial markets are having on worldwide eco-
Ingelheim. This makes it the most important
nomic systems and thus on the pharmaceutical
business segment within the group of compa-
11
Group Management Report
nies. With adjustments for currency effects,
the results of the ontarget™ study. With
growth of more than 9 % was achieved in the
f lomax®, used in the treatment of benign pros-
2008 financial year, thereby following up on the
tatic hyperplasia (BPH), sales increased by 5 %.
positive development of the previous years.
The share of this medication in the US market was once again around 60 %. We obtained
Net sales (in millions of EUR)
market approval for pradaxa® (dabigatran 2008
2007 Change
Prescription Medicines
9,111
8,660
+5.2 %
Consumer Health Care
1,190
1,141
+4.3 %
Biopharmaceuticals
569
463 +22.8 %
Pharma Chemicals
etexilate), our new oral direct thrombin inhibitor. Initial sales in 2008 fulfilled our expectations for the medicine, which was developed by us, and allow us to be optimistic for the future. Our Consumer Health Care business achieved
and Pharmaceuticals Production
250
276
-9.4 %
Animal Health
467
408 +14.4 %
further growth last year and recorded total sales of around EUR 1.2 billion. On a local basis, this corresponded to growth in sales of 5.4 %. The most important brands, each of which achieved
The development of sales in the Prescription
sales of over EUR 100 million, were once again
Medicines segment was driven by the pleasing
dulcolax®, mucosolvan® and pharmaton®.
development of our strategic products, as in
buscopan® showed excellent growth in the
the preceding years. Our blockbuster products
2008 calendar year and almost reached sales of
that each generate sales of over USD 1 billion,
EUR 100 million. Overall, the core CHC brands
spiriva®, micardis®, flomax® and sifrol®/
showed very pleasing development.
mirapex®, achieved sales of more than EUR 5 billion in 2008 and grew on average by more than 10 % compared with the previous year.
After our Animal Health business already achieved excellent growth in 2007, the previous year’s figures were significantly exceeded once
Our innovative COPD medication spiriva®
again in 2008. With growth in sales of 14.4 %
increased its worldwide sales by 16 % to EUR
(19.5 % based on local currencies), we strength-
2,070 million in 2008 and thus achieved sales
ened our position on the market further and are
of more than EUR 2 billion for the first time.
in eighth place with a (provisional) worldwide
This means that it is once again the product with
market share of 3.5 %. The growth engine in the
the highest sales at Boehringer Ingelheim. The
Animal Health segment was our own develop-
results published from the COPD milestone
ment ingelvac circoflex®. Sales of the vac-
study uplift® will further strengthen the mar-
cine for pigs grew by more than 140 % to around
ket position of the anticholinergic. The primary
EUR 90 million.
growth engine within the group of products considered to be the most important by the
In our Biopharmaceuticals business, sales in-
group was sifrol®/mirapex®, with growth in
creased following a decline in 2007, owing to
sales of 17 %. In an intensely competitive market
alterations and extensions at our production site
segment, micardis®, a medicine for the treat-
in Biberach. With growth of over 20 % to EUR
ment of high blood pressure, increased its sales.
569 million, the best sales in the history of this
Further growth is also expected here following
business segment were achieved in 2008.
12
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
In 2008, we were able to build on the success of
ents, which represents around 18.2 % of group
previous years, which confirms our strategic
sales (2007: 17.4 %). A total of EUR 2,016 million
orientation. With innovative products, supple-
was spent in 2008 on research and development
mented by an extensive pipeline with promising
in the Prescription Medicines segment, the focus
new developments and motivated staff, we are
of our R&D activities (22.1 %).
ready for the challenges ahead and look to the future with confidence.
Our own research forms the basis for our R&D strategy. In addition, our portfolio is extended
Operating income decreased in the last financial
through targeted in-licensing and cooperations.
year. This was essentially due to the dispropor-
One important addition in the last financial year
tionately large increase in R&D costs (+11 %) and
was the partial acquisition of the biopharmaceu-
burdens caused by the unfavourable develop-
tical company Actimis Pharmaceuticals, Inc,
ment of the US dollar in 2008.
based in San Diego (California), USA. The com-
The most important earnings figures for 2008
for the treatment of asthma, AP768, which is
pany owns a leading active ingredient candidate are as follows:
currently in phase I of clinical development. Even before the current clinical trial, AP768 had
(in millions of EUR) Net sales Operating income
2008
2007
Change
11,595 10,952
+5.9 %
1,980
2,100
17.1
19.2
Return on net sales (as %)
-5.7 %
been proven to possess the potential for more effective mechanisms of action than the leukotriene receptor antagonists currently available on the market. We continued our successful partnerships with the Belgian biotechnology company Ablynx NV, for research into Nanobodies®,
Research and development
the US company Xencor, Inc. (biological active
In line with our vision as a pharmaceutical
ingredients), the British company Vectura (pow-
research company, we are firmly convinced that
der inhaler) and the US company Vitae Pharma-
innovation will also in future continue to be an
ceuticals (11beta-HSD1 inhibitors).
important driving force behind our growth. Our personal and financial commitment is therefore
In accordance with our current strategy, we carry
to research into new and innovative active ingre-
out drug discovery and development at the four
dients for the treatment of diseases for which
previously mentioned R&D sites in seven major
only inadequate medical therapies are current-
therapeutic areas:
ly available. We are therefore intent on both strengthening our core business and to pressing
• cardiovascular diseases
ahead with the optimisation of our current prod-
• respiratory diseases
uct portfolio.
• central nervous system diseases • metabolic diseases
In the last financial year, an average of 6,788
• virological diseases
persons were employed at our R&D sites in
• oncology
Germany, the USA, Austria and Canada. In total,
• immunology and inflammation
over EUR 2.1 billion were invested here in the development and research of new active ingredi-
13
Group Management Report
In the field of the treatment and prevention of
thrombo-embolic diseases, we achieved crucial
alteplase (actilyse®) is safe and effective even
success, confirming our commitment to R&D.
after the end of the permitted 3-hour window.
pradaxa® (dabigatran etexilate), our new oral
According to the study, patients can benefit from
direct thrombin inhibitor, an active ingredient
alteplase up to 4.5 hours after the first symp-
developed by Boehringer Ingelheim and the first
toms of stroke begin. We are therefore aiming to
with a new kind of mechanism of action, has
extend the approval for actilyse®. The signifi-
obtained market approval for Europe and for a
cance of this result is emphasized by the fact that
growing number of countries outside Europe.
the international medical journal The Lancet
Approval was initially granted for the preven-
has chosen the publication of this study as
tion of venous thrombo-embolism (VTE) fol-
“Paper of the Year 2008 (editors’ choice).”
lowing hip and knee replacement surgery. With the re-volution® clinical trial programme, in
In profess®, the largest study so far into the
which over 30,000 patients are participating
secondary prevention of stroke, the effectiveness
worldwide, we are aiming to obtain approval for
of the fixed combination of delayed dipyrida-
further indications. These include the preven-
mole/ASA (aggrenox®) was compared with
tion of strokes in patients with atrial fibrillation
clopidogrel. The results of the study showed that
(re-ly™: over 18,000 patients worldwide), the
the risk of a further stroke is comparable for the
treatment of acute VTE (re-cover™) and the
two treatment options. The combined risk of
secondary prevention of VTE (re-medy™) as
stroke, myocardial infarction and death due to
well as acute coronary syndrome (re-deem™).
vascular diseases was also comparable.
In 2008, several major trials for the indications
With the results of the ontarget™ study we
of central nervous system diseases and cardio-
were able to prove that telmisartan (micardis®),
vascular diseases were concluded.
our angiotensin II receptor blocker (ARB), protects high-risk patients against cardiovascular
The ecass 3™ study proved that in the treatment
events just as well as the current gold standard,
of acute ischaemic stroke, thrombolysis with
ramipril. In a direct comparison, telmisartan
Research and development
2008*
2007
2006
2005
2004
Expenditure in millions of EUR
2,109
1,900
1,574
1,360
1,232
18.2
17.4
14.9
14.3
15.1
2,016
1,818
1,501
1,293
1,173
- as % of net sales Prescription Medicines expenditure in millions of EUR - as % of Prescription Medicines net sales Average number of employees
22.1
21.0
18.1
17.8
19.0
6,788
6,405
6,003
5,678
5,471
145
157
125
116
97
Investments in tangible assets (without investments in infrastructure) in millions of EUR
*As of the year under review, costs for phase IV clinical trials are included in R&D costs, among other expenses. The previous year’s figure was adjusted accordingly.
14
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
also proved to be significantly better tolerated.
Production
The results were confirmed by transcend®, a
Boehringer Ingelheim has a worldwide network
parallel study to ontarget™, in which almost
of 23 production sites for Human Pharmaceuti-
6,000 patients from 40 countries participated.
cals. Pharmaceuticals Production is the main
transcend® is the first milestone study in
focus with 18 sites. There are also additional
which the cardiovascular protective effects of an
production sites for Pharma Chemicals and Bio
angiotensin II receptor blocker were tested and
pharmaceutical Production.
proved against a placebo in addition to standard treatment in high-risk patients with intolerance
Pharmaceuticals Production is responsible for
to angiotensin-converting enzyme (ACE) in
the manufacture of our own products in the
hibitors.
Human Pharmaceuticals business. Boehringer Ingelheim has also established itself as a con-
In the field of respiratory diseases, the beta-
tract manufacturer for external partners through
agonist bi 1744 successfully completed clinical
its excellent quality of service. In 2008, the oral
phase II. A large-scale phase III trial has been
thrombin inhibitor pradaxa® was successfully
commenced. A supplementary phase II trial is
launched by our Pharmaceuticals Production
also underway for the fixed combination of
division in Ingelheim. The introduction of inno-
bi 1744 and tiotropium (spiriva®) in r espimat®,
vative products makes particular demands on
our already very successful long-acting anti-
the quality of processes. At our launch sites in
cholinergic for the treatment of chronic obstruc-
the USA and Germany we have the specialist
tive pulmonary disease (COPD). We expect the
knowledge needed to ensure that products are
combined programme to enter clinical phase III
made just in time. The LogiPack-Center at the
in 2009.
Ingelheim site in Germany will make a significant contribution to this in future. Through an
In 2008, we also received the results of our
investment of EUR 49 million, we have created a
COPD milestone study uplift®. These show that
highly modern and extremely efficient packag-
treatment with tiotropium leads to a lasting im-
ing centre, which will give us further competi-
provement in lung function over four years and
tive advantages. In addition, around EUR 65
increased survival rate. 5,993 male and female
million has been invested in a first module for
patients with COPD took part in the study.
the production of pradaxa®. We will continue
In the field of diabetes treatment, our compound
for the expansion of our capacity, in order to
to make funds available in the next few years bi 1356 (ondero®), a DPP-4 inhibitor, success-
guarantee the supply of the market and to fulfil
fully entered clinical phase III. All the necessary
increasing regulatory conditions.
studies for approval for the indication of type 2 diabetes were commenced worldwide. Our
We aim to improve efficiency and flexibility
development programmes in the field of oncol-
within our production network in order to
ogy are also on schedule. Further progress
remain competitive in future. Our product costs
has been made here with the preparation and
are competitive and at a low level compared
commencement of phase III trials for the two
with the rest of the industry. The results of a
compounds bibw 2992 and bibf 1120 (desig-
business process excellence initiative and
nated brands tovok® and vargatef®).
insights gained from tried and tested methods
15
Group Management Report
such as lean manufacturing support our actions.
guarantee the practical implementation of our
In connection with this, we sold our production
principles. The minimum standards for this are
site in Reims, France. Our decision will ensure
the legal requirements of the respective coun-
future growth for the site and will guarantee
tries in which we operate, which we naturally
Boehringer Ingelheim a long-term supply of
respect and observe. With issues that we regard
high-quality products.
as meaningful and essential, we even aim to ex-
At Pharma Chemicals, we continued with the
Compliance with our principles and their suc-
ceed the requirements defined by legislators. expansion of capacity at our sites in Fornovo,
cessful implementation is ensured through es-
Italy, and Petersburg, USA, especially for the
tablished processes in the Environmental, Health
production of captive active ingredients. Invest-
& Safety (EHS) division. In 2008, for example,
ment projects at the two sites with a total volume
11 audits were carried out in which various sites
of around EUR 160 million will be completed in
were checked to ensure their compliance with
2009. In the next few years, further investments
the guidelines issued and the correct function-
in chemical production totalling over EUR 490
ing of the systems. Along with statutory and
million are planned.
internal regulations, Boehringer Ingelheim has also committed itself to following the principles
Boehringer Ingelheim has been involved in the
that apply as part of the worldwide “Responsible
development and manufacture of biopharma-
Care” initiative in the chemical industry.
ceutical products for over 20 years. Our sites in Vienna, Austria, and Biberach, Germany, have
One of Boehringer Ingelheim’s major projects in
since then developed 14 new biological entities
the field of energy efficiency in 2008 was the
(NBEs) into marketable products. This makes
inauguration of the cold water storage facility at
us one of the most experienced contract manu-
our site in Biberach. This is one of the largest
facturers in biopharmaceuticals. Total invest-
of its kind in Europe and makes a lasting contri-
ments of approximately EUR 60 million in 2008
bution to the protection of the environment. In
and planned investments of over EUR 400 mil-
addition to the economic advantages, around
lion for the next few years underline the
2,100 tons of carbon dioxide emissions can be
importance of biopharmaceutical production for
avoided per year and the consumption of water
Boehringer Ingelheim.
at the site can be reduced by 21,500 m³ per year.
Environmental and employee protection
An important indicator of occupational safety at
The protection of our employees, our facilities
our sites is the accident rate relative to hours
and our environment from harmful influences,
worked. Through continual improvements, we
the conservation of natural resources and the
have managed to reduce the number of accidents
promotion of environmental awareness are of
to an average of 3.4 accidents for every million
central importance to Boehringer Ingelheim.
hours worked.
This is made particularly clear by the anchoring of this principle in our company’s Leitbild.
The certification of our production sites by
Group-wide standards relating to occupational
part of our environmental and safety manage-
safety and the protection of the environment
ment in 2008. After our chemical plants in
external organisations was also an important
16
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
France and Italy, our site in Malgrat, Spain, also
aim to continue recruit the best employees in
received ISO 14001 certification, thereby con-
future and tie them to us in the long term.
firming the quality of our internal standards.
For this purpose, wide-ranging opportunities
The site in Fornovo, Italy, achieved the objective
for further development are available to our
of total quality management with the OSHA
employees. We offer particularly talented
18001 certification of its safety management.
employees challenging measures for the advancement of their social and managerial skills.
Employee reporting
Programmes with an international focus, such
As in the preceding years, the average number of
as the “International Management Development
employees rose in 2008. On average, 41,300 per-
Program” (IMDP), are also available as part of
sons were employed at Boehringer Ingelheim
the “BI Academy”.
during the year, which represents growth of 3.8 % compared with the previous year. The
We believe that we are in a good competitive
group’s personnel costs rose by 4 % in 2008.
position with our remuneration system. In addition to the basic salary that is usual for the
Allowing young people to make a successful start
market, we have established a performance-
to their professional lives has traditionally been
related salary component, which represents a
a matter of particular importance to Boehringer
significant part of remuneration. The size of the
Ingelheim. In the period under review, we
performance-related pay depends essentially on
offered 673 young people an apprenticeship pro-
the success of the company and the attainment
gramme at our three German sites (2007: 660).
of individual targets. Extensive benefits, such as
Thereby we pay special attention to the goal of
company pension schemes and preventive health
also enabling young people with handicaps to
checks, also make our overall remuneration
participate in these apprenticeship programmes.
system more attractive.
Boehringer Ingelheim’s employees are the most
The creation of an excellent framework for the
important factor in the future success of the
compatibility of career and family is of major
company. We therefore believe we have a special
concern to Boehringer Ingelheim. An important
commitment to the active further development
instrument for the systematic and future-
and promotion of their abilities, in order to be
oriented creation of a family-friendly corporate
equipped as well as possible for the challenges
culture is the “audit berufundfamilie” of the
that lie ahead. As part of the annual “Value
Hertie Foundation. Following basic certification
through Innovation Day” (VTI Day), proposals
in 2005, we received recertification/re-auditing
for improvements on the subject of coaching and
in the last financial year. We will continue to
development were drawn up at our head office
promote a family-friendly management culture
in Ingelheim and have already begun to be im-
in future and will support our employees with
plemented.
balancing work and family life.
Following the first worldwide employee survey
In 2008, Boehringer Ingelheim was once again
in 2007, we also used the insights gained to
among the top companies in several surveys
implement improvements. A second survey will
identifying the best employers. The awards that
be carried out in 2009. All personnel measures
have been received in many countries confirm
17
Group Management Report
the attractiveness of our company and are also a
medication essential for survival. Another im-
continual incentive to offer our employees an
portant issue that we are involved in as a com-
excellent working environment in future.
pany is dealing with demographic change. In Germany, Boehringer Ingelheim has since 2006
Corporate responsibility
supported the construction of premises that
Commitment to society and awareness of social
bring the generations together in the city of
responsibility have been firm components of
Ingelheim and has provided assistance as a co-
Boehringer Ingelheim’s corporate culture for
operation partner with planning and implemen-
over a century. We regard ourselves, both in
tation.
economic and in social matters, as an active promoter of welfare in the countries and regions
In addition to our company’s commitments,
in which we operate. As a “good corporate citi-
many of our employees are involved in numer-
zen”, we actively fulfil our responsibility towards
ous social projects on a voluntary basis in their
society as a whole, our patients, our employees
free time. We believe their personal commitment
and their families and with a high level of com-
is the expression of a basic attitude that matches
mitment.
Boehringer Ingelheim’s understanding of itself and that we will promote and support where
One focus of Boehringer Ingelheim’s charitable
possible. During a special promotion day
work is combating the HIV/AIDS pandemic in
employees from Ingelheim, for example, were
the most severely affected countries. With our
able to obtain information on important sub-
Donation Programme, we have provided our
jects concerning voluntary work and care.
AIDS medication viramune® free of charge since 2000, which significantly reduces the risk of transmission of HIV between mother and child during birth. In this way, 169 individual support programmes have been set up in 59 countries since the beginning of the initiative. We observe our social responsibility in other
Results from operations, financial position and net assets
international initiatives geared towards the particular needs of people in various countries
Results from operations
and regions. In the USA, the Boehringer Ingel-
Last year, Boehringer Ingelheim was once again
heim Cares Foundation provides free medical
one of the fastest-growing companies worldwide
care together with AmeriCares. Employed peo-
in its reference group. This is shown by the
ple living below the poverty line, who would
market data currently available, according to
otherwise not receive any medical care, are
which our growth was once again well above
looked after here. In the province of Sichuan in
that of the worldwide pharmaceutical market.
south-western China, which was devastated by
We were again in a position to achieve growth
earthquakes, we supported affected people
organically and with products from our own re-
in cooperation with a local partner, the R&D-
search and development. According to the latest
based Pharmaceutical Association Committee
market data, Boehringer Ingelheim has a world-
(RDPAC), with both donations of money and
wide market share of approximately 2 %.
18
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Boehringer Ingelheim increased its net sales by
Prescription Medicines
5.9 % in the last financial year to EUR 11,595
Within our Human Pharmaceuticals business,
million. Growth in local currency terms was
the Prescription Medicines segment represents
even as high as 9.5 % (2007: 8.8 %). This means
the focus of our activities. In relation to the
that the development of our sales in 2008 in
Human Pharmaceuticals business as a whole,
euro terms was again impaired by unfavourable
the segment represents around 82 % of sales.
developments in exchange rates. After the US
Sales of Prescription Medicines totalled EUR
dollar showed considerable weakness in the
9,111 million in 2008, following sales of EUR
previous year, this trend continued in 2008.
8,660 million in the previous year. With growth
Compared with its average value in 2007, the US
in sales of 5.2 % (growth in local currencies:
currency declined in value by around 7 %.
9.3 %), the previous year’s growth (2007: 4.2 %)
Because of the high proportion of our sales in
was exceeded.
this currency region (over 35 %), a burden of around EUR 365 million was placed on group
Our strategic products, all of which recorded
sales. Without these negative effects, the group’s
positive growth, made a significant contribution
sales in 2008 would have totalled almost EUR
to this development (sequence in order of sales):
12 billion. As in previous years, there were no significant changes in 2008 in the companies to
Net sales
be consolidated, which means that any effects
(in millions of EUR)
2008
spiriva®
2,070
1,792
+16 %
micardis® (*)
1,219
1,059
+15 %
flomax®
from this on the analysis of sales are negligible. Boehringer Ingelheim is focused on two businesses: Human Pharmaceuticals and Animal Health. Human Pharmaceuticals encompasses the segments Prescription Medicines (PM), Consumer Health Care (CHC) as well as Indus-
2007 Growth
1,075
1,020
+5 %
mirapex®/sifrol®
752
644
+17 %
aggrenox®
313
278
+12 %
*As of 2008, without sales from business with partners. The previous year’s figure was adjusted accordingly.
trial Customer. In 2008, Boehringer Ingelheim’s Human Pharmaceuticals business generated
Boehringer Ingelheim thus has four products
total sales of EUR 11,128 million. This represents
with sales of over USD 1 billion, all of which
growth of 5.5 % compared with 2007. The pro-
underlined their potential through further
portion of group sales that comes from Human
growth in the last financial year. mirapex®/
Pharmaceuticals is 96 %.
sifrol® achieved the highest growth rate in
2008
2007
2006
2005
2004
Price/quantity/new introductions
9.7
7.9
12.1
17.4
16.1
Acquisitions and sale of business
-0.2
0.9
-0.3
-0.5
-0.5
Currency effect
-3.6
-5.2
-0.9
0.0
-5.1
Components of growth in net sales (as %)
19
Group Management Report
2008. With regard to sales and in terms of abso-
Net sales
lute growth, spiriva® is our most important
(in millions of EUR)
product, as in the previous year. The market position of our COPD blockbuster was further strengthened by the results of the milestone study uplift®, which were published in 2008. We expect spiriva® to remain our main growth engine in the next few years. Our products
2008*
2007* Growth
dulcolax®
134
125
mucosolvan®
125
117
+7 %
pharmaton®
115
95
+21 %
99
80
+24 %
buscopan®
+7 %
*As of 2008, switch to presentation of brands. The previous year’s figures were adjusted accordingly.
m icardis® and aggrenox®, for which important studies were also concluded in 2008
The Europe region represented the highest share
(profess®, ontarget™ and transcend®), also
of sales in the CHC segment at Boehringer Ingel-
showed pleasing development and each recorded
heim, with sales of EUR 480 million (+2.1 %).
double-digit growth.
With regard to growth in sales, the AAA region
In the Prescription Medicines segment, regional
with sales of EUR 364 million in 2008. The
achieved the strongest growth rate of 10.5 %, development varied considerably. While the
Americas region increased its sales to EUR 347
Europe (+EUR 265 million) and Asia, Austral
million, which represents growth of 7 % in local
asia, Africa (AAA) regions (+EUR 135 million)
currencies.
grew, sales in euro terms in the Americas region remained at the same level as the previous year,
Industrial Customer
owing to the exchange rate development. Based
The third party business of Pharmaceuticals
on local currencies, however, our business grew
Production, Pharma Chemicals and contract
by 6.8 % in the Americas region. The countries
manufacturing by Biopharmaceuticals are com-
with the highest sales in this segment are the
bined under Industrial Customer business. In
USA, followed by Japan and Germany. Net sales
total, sales in this business segment amount to % share
EUR 819 million, around 11 % higher than in the previous year. However, this increase is mainly
2008
2007
in 2008
Americas
4,495
4,502
49 %
site in Biberach, Germany, for technical altera-
Europe
2,640
2,374
29 %
tions and extensions, which had a negative
AAA
1,581
1,446
17 %
impact on sales in the previous year. With sales
9,111
8,660
(in millions of EUR)
due to the temporary closure of our production
of EUR 569 million, contract manufacturing of biotechnologically produced medication forms
Consumer Health Care (CHC) In our business segment Consumer Health Care, we increased net sales by 5.4 % compared with the previous year, discounting currency effects. Sales for 2008 totalled EUR 1,190 million (2007: EUR 1,141 million). Sales of our core international brands showed positive development (in order of sales):
20
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
the focus of our Industrial Customer business. Animal Health In our business Animal Health, we increased our sales to EUR 467 million. This represents growth of 14.4 % compared with the previous year – without taking into account negative currency effects. With adjustments for currency effects, the Animal Health business recorded growth in
sales of 19.5 %. This makes us one of the fastest-
Depreciation increased by 4 % compared with
growing companies in the field of animal health
2007 and amounted to EUR 524 million (2007:
and puts us well above market growth of
EUR 504 million). Other operating expenses in-
approximately 4.7 % (according to provisional
creased to EUR 5,198 million, which represented
market data). This remarkable success is largely
a rise of EUR 731 million (+16 %) compared with
due to our product ingelvac circoflex®,
the previous year. This included payments of
which achieved sales of around EUR 90 million
commission to our sales partner Pfizer, which
in 2008. Sales of the PCV2 vaccine (porcine
grew in line with the increase in sales of spiriva®.
circovirus type 2) for pigs thus more than
Operating income fell compared with the previ-
doubled compared with the previous year.
ous year and amounted to EUR 1,980 million. The return on net sales was also below the previ-
In particular, the following product groups
ous year’s level at 17.1 %, owing to additional
contributed to worldwide growth:
efforts in Research & Development (+EUR 209 million) and the negative currency effects already mentioned.
Net sales (in millions of EUR)
2008
2007 Growth
ingelvac circoflex®
90
37
> 100 %
vetmedin®
29
24
+24 %
ingelvac® m. hyo
27
23
+14 %
metacam®
78
77
+1 %
The financial result amounted to EUR -40 million in 2008, which corresponds to a drop of about EUR 300 million compared with the previous year. This was largely due to the share of interest in additions to pension provisions and the sale of some financial assets in the previous
Impressive growth of 44.4 % was achieved in the
year. As a result, income before taxes amounted
AAA region. In particular, developments on the
to EUR 1,933 million.
Japanese and Chinese markets contributed to this success. Our sales also showed positive
Tax expenses amounted to EUR 505 million.
development in the other regions. We have a
Here, it must be taken into consideration that,
share of 3.5 % in the global market for animal
due to regulations of the German commercial
health products (based on provisional market
code, personal taxes on group activities levied
data).
on the shareholders must not be shown as tax
Expenditure and income
drawals from accumulated group equity. Taking
Operating expenses were up by 9.3 % on the
this extraordinary effect into consideration, the
previous year, at EUR 10,368 million (2007:
actual tax burden is markedly higher than the
EUR 9,484 million). Material costs amounted
figure shown in the profit and loss statement.
expenses. These are presented as part of with-
to EUR 1,642 million, which represents a slightly lower proportion of total sales of 14.2 %.
Overall, the increase in sales did not compensate
Personnel costs rose by EUR 118 million in 2008
for the effects of other operating expenses and
and totalled EUR 3,004 million (+4 %). This
the financial result. In summary, net income
increase was mainly due to a higher average
totalled EUR 1,424 million and was therefore
number of employees, with around 1,500 addi-
lower than in the previous year (EUR 1,809
tional staff.
million).
21
Group Management Report
Financial position
high cash flow from operating activities, all the
Boehringer Ingelheim’s financial management
prerequisites for the successful implementation
instruments and methods are aligned with in-
of our strategy are still fulfilled.
ternational standards for a modern industrial company. The aim is to support the business
In 2008, several investment projects were com-
strategy of our company by providing or invest-
pleted at our sites in Germany and new projects
ing financial assets and taking account of the
were initiated. At our launch site in Ingelheim,
foreign exchange risk.
the first module for the production of pradaxa®
As a result of Boehringer Ingelheim’s interna-
centre (LogiPack-Center) was also officially
should be mentioned here. A new packaging tional orientation, exchange rate fluctuations
opened. In Biberach, a logistics centre and a kilo
have a considerable impact on the measure of
laboratory for chemical development were
the company’s success. The exchange rate devel-
opened. A cold water storage facility to supply
opment of the US dollar represents the highest
the Biberach plant was also put into service. At
single risk. Within the framework of group-wide
our sites abroad, we continued with necessary
financial reporting, foreign exchange risk is reg-
extensions to capacity.
ularly investigated and systematically analysed. To secure against risks from goods and services
Net assets
and other risks, derivative financial instruments
Total assets increased by EUR 1,352 million to
are employed. The manner and extent of these
EUR 11,824 million in the last financial year.
measures are regulated by the relevant group
Intangible and tangible assets totalled EUR
guideline.
3,716 million and are completely covered by Boehringer Ingelheim’s group equity.
Cash flow for the period under review amounted to EUR 1,997 million. Cash flow from operating
Financial assets amounted to EUR 1,739 million
activities dropped to EUR 1,901 million, which
at the end of the year, a slight increase on the
was mainly due to the lower income for the
previous year. The increase in inventories was
period under review. It is, however, still consid-
slightly larger than the increase in group sales,
erably higher than the funds used for investment.
with adjustments for currency effects. Among
A total of EUR 665 million, which is similar to
other factors, this is due to the creation of initial
the previous year’s level, was spent on invest-
stocks for new product launches, such as
ments in tangible assets in 2008. Investments in
pradaxa®. Trade accounts receivable developed
intangible assets declined. Financing activities
in proportion to growth in our business, with
resulted in an outflow of funds of EUR 935 mil-
adjustments for currency effects. This was
lion, which was largely due to the repayment of
achieved through active management of the
loans. In total, financial assets increased by EUR
duration of our receivables. Liquid funds
351 million to EUR 2,932 million (+13.6 %). There
(including current securities) totalled EUR 1,312
were no changes to cash flows as a result of the
million, which represented a significant increase
crisis on the international financial markets.
(2007: EUR 1,015 million).
In summary, it can be emphasised that with the
Group equity rose by 38 % to EUR 4,893 million.
existing liquidity, the financial structure and
The increase in this item is almost entirely due to
22
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
the retained profit for the year. Long-term disposable capital (equity, pension provisions and
Risk report
long-term liabilities) increased to EUR 7,289 million. This corresponds to around 62 % of the
The Boehringer Ingelheim group’s risk manage-
group’s total assets. This means that all intangi-
ment system has proved effective over recent
ble assets, tangible assets, inventories and some
years and the concept was unchanged in the
trade accounts receivable are once again covered
reporting period. We have an established risk
by this item.
management system that aims to recognise risks
Other provisions increased to EUR 2,290 mil-
level. When looking at the risks identified, we
lion (+16 %). This is partly due to the increase in
endeavour to take into account the business
provisions for anticipated losses on derivative
opportunities that arise on the other hand and to
financial transactions, owing to the rate prevail-
include them in the analysis.
and reduce them where possible to a reasonable
ing on the reporting date. Translation effects when converting annual accounts, for example
The task of the group-wide risk reporting and
in Japanese yen, also contributed to the rise.
messaging system at Boehringer Ingelheim is to
Liabilities also fell to EUR 1,761 million (2007:
systematically identify risks specific to the busi-
EUR 2,151 million), which was essentially due to
ness, particularly risks that threaten the survival
the repayment of loans.
of the company. Hereby, we ensure that all risks known to us are reported, thoroughly analysed
The combined evaluation of the net assets,
and evaluated at all times. Following appropri-
financial position and results of operations
ate classification, adequate counter-measures
shows that Boehringer Ingelheim is a soundly
are commenced and their implementation con-
financed and profitable company. In 2008, we
sistently monitored.
created a solid basis for our further business development.
Internal auditing conducted routine and extraordinary audits worldwide in 2008. The major focus is on the efficiency of structures and processes, securing assets, adherence to legal and internal requirements and guidelines, the
Report on post-balance sheet date events
functionality of systems and the effectiveness of internal controls. The audit plan approved by the Board of Managing Directors was consistently followed.
Since the end of the financial year 2008, we have not become aware of any events that are of
Against the background of the financial crisis,
material significance to the group of companies,
potential risks for Boehringer Ingelheim were
or could lead to a reappraisal of its asset, finan-
analysed and evaluated in detail. No extraordi-
cial or earnings position.
nary risks to the company were identified, either with regard to receivables or in terms of liabilities. We will continue to follow overall economic developments and the effects of the financial
23
Group Management Report
crisis very closely, in order to identify possible
from this largely confirm our strategic guide-
risks at an early stage. Currency and interest rate
lines and objectives. The extend of the effects of
risks that arise because of our group’s interna-
the current developments in the worldwide
tional business relationships are examined at
economy, which, triggered by the crisis on the
regular intervals and limited by appropriate
financial markets, have led to a lasting decline
hedging strategies, such as foreign exchange for-
across all branches of industry cannot yet be
ward contracts and foreign exchange options.
calculated for the pharmaceutical industry. We
We are not aware of any default risks going
expect the slowdown in the growth rate, which
beyond the usual level for the market. Our hedg-
has been apparent for years, to intensify as a
ing strategies are used essentially for economic
result of the difficult overall economic condi-
and political risks.
tions.
Risks in the area of environmental health and
Our core brands spiriva®, micardis®, flomax®
safety (EHS) are minimised preventively by
and mirapex®/sifrol® will continue to achieve
adherence to our own very high safety standards.
stable growth in 2009. The results of the clinical
Appropriate emergency plans have been drawn
trials of spiriva® and micardis® that were pub-
up for possible incidents and are regularly
lished in 2008 confirmed the potential of these
practised and tested in terms of their quality. In
two products and will provide the basis for
addition, Boehringer Ingelheim has insurance
further sales growth in 2009. Our stable product
coverage adjusted to the company’s risk profile.
portfolio therefore allows us to view the challenges of 2009 with confidence.
Apart from general business risks associated with the industry as, already outlined in detail,
In the field of clinical development, we are an-
such as patent expiry, governmental price regu-
ticipating further important milestones in 2009,
lations and launches, we are currently not aware
such as the completion of the re-ly® study, the
of any risks that substantially threaten the fur-
largest in the re-volution® trial programme
ther development of Boehringer Ingelheim’s
for our innovative oral coagulation inhibitor
business.
pradaxa®. We expect the study to be completed in the first half of 2009, earlier than originally planned. Other important development programmes in the indications of oncology, for the active ingredients bibw 2992 and bibf 1120
Report on expected developments
(designated brands tovok® and vargatef®), and metabolic diseases, for the active ingredient bi 1356 (ondero®), will be continued in 2009. We also expect the results of the bouquet®
The good results for the last financial year con-
phase III trial programme to provide an impor-
firmed our internal planning guidelines. Our
tant stimulus for the approval of our research
operations and functions revised and validated
compound flibanserin in 2009. Flibanserin is
the existing strategic guidelines during the
being investigated in the treatment of decreased
period under review, within the framework of
sexual desire in women (HSDD: hypoactive
our planning processes. The insights gained
sexual desire disorder).
24
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
For the 2009 financial year, we are anticipating
continuing to achieve our ambitious goals. We
further single-digit sales growth, despite the
consider it an obligation to our customers to
overall economic uncertainty mentioned above.
make effective and safe medicines available in the future.
The challenges inherent in the pharmaceutical research industry also apply to Boehringer Ingelheim. In addition to increasing cost pressure in health systems, which are less and less willing to provide adequate remuneration for the high cost of innovation, other challenges include those caused by the expiry of patents (or attacks on patents by generic drug manufac turers) and the need to develop new innovative products successfully to market launch. With the development projects mentioned and further approval stages expected in 2009, we believe that we are well-equipped to deal with the anticipated arrival of rival generic versions of the products flomax® and mirapex®/sifrol® in 2010. We have planned investments of over EUR 900 million for the 2009 financial year, which means that the level of investment will be well above that of the previous year. Our investment focuses mainly on production and research. The main emphasis of our activities is on worldwide projects to expand capacity in order to ensure a market supply for our new product launches. For Boehringer Ingelheim, the declared goal is to continue running the company as an independent, family-owned company in the long term. We believe that our high level of innovation, which is based on a well-filled pipeline that will lead to a series of new product launches in the next few years, provides the basis for aboveaverage long-term growth. Against this background, we will not only focus on successful market launches but we will also continue to pay particular attention to our company’s profitability. Our strategic orientation is focused on
25
Group Management Report
Contents
} Saying it with flowers } Corporate Responsibility } Caring for patients – The viramune® Donation Programme } Caring for our neighbours – “We Care” } Environmental protection and occupational safety } Our people
26
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Corporate Responsibility
lena gresser Her handicap is no obstacle to receiving a proper vocational qualification.
28
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
corporate responsibility
Saying it with flowers
Lena Gresser, a cheerful 22-year-old woman, travels to work by train by herself from her hometown Mainz to Boehringer Ingelheim’s main German site at Ingelheim, just a short distance along the River Rhine. She is training to be a florist in the company’s property and garden maintenance department, which looks after a sprawling mix of production facilities, offices and laboratories in a park-like setting. And the fact that she has Down’s syndrome is not preventing her from blossoming in her vocation. The pilot project Lena is involved in aims to show that her handicap is no obstacle to receiving a proper vocational qualification. And the company, with important support from a number of outside agencies, has integrated Lena fully into a working team of 30 people. Her strong motivation, enthusiasm for work and reliability have greatly impressed her colleagues. “I really love coming to work,” says Lena. “Every day I learn something new, and working with flowers is what I’ve always wanted to do.”
Making Lena’s ambition to be a florist come true
tives respectively from the company and the staff
calls for long-term commitment by Boehringer
responsible for matters involving handicapped
Ingelheim and, more specifically, the team in
people.
which Lena has been embedded. Master gardener Pia Winter, a lady well-known at Boehringer
The project for Lena, which started in 2008, is
Ingelheim for her green fingers, plays a lead role
just one example of the active corporate respon-
in providing support for Lena. Her close mentor-
sibility of Boehringer Ingelheim. It is the first of
ing of the trainee and fostering of her strengths
its kind in Rhineland Palatinate, the federal state
and talents is having a decisive impact on Lena’s
in which Boehringer Ingelheim is located. This
progress. Key support is also provided by Olaf
makes it only the second time in Germany that
Guttzeit and Doris Müller, special representa-
such a project has been initiated. The outside
29
Saying it with flowers
agencies supporting the project include the ZSL
Caring for patients – The viramune® Donation
Zentrum für selbstbestimmtes Leben (Centre for
Programme
Independent Living) in Mainz and the PEp Praxis für Entwicklungspädagogik (The Development Pedagogy Practice). Lena’s parents have also helped in drawing up the project concept that is also supported by the Labour Agency. Pia Winter, whose personal commitment and understanding is highly appreciated by everyone involved in the
We have an overarching commitment to combating the devastating AIDS pandemic.
project, is very pleased with the way in which Lena’s self-esteem has increased with recogni-
Our viramune® Donation Programme has for
tion of her work and the appreciation of her as a
eight years provided our non-nucleoside reverse
valuable member of the team. “She’s a highly
transcriptase inhibitor viramune® (nevirapine)
motivated young woman when it comes to learn-
to target the prevention of mother-to-child trans-
ing. And what’s wonderful to see is how much
mission of the HIV-1 virus in the countries most
more independent she is becoming.” l
in need. By 2008, this programme extended to 169 schemes in 59 countries.
Corporate Responsibility
For more information, please see www.boehringer-ingelheim.com/
The ethical principles that have guided our company for well over a century have created a culture of corporate responsibility and commitment. Corporate responsibility, as practised by our company, takes many forms. Of paramount import ance for us are the needs of patients. It is the quest for innovation and medical breakthrough which drives all our activities. We understand
corporate/news/information_material/ hiv_policy_paper.pdf l
Caring for our neighbours – “We Care”
Our activities cover many areas, including child protection, healthcare projects, educational programmes, environmental protection and emergency aid.
that the importance of our company directly depends on the value of the therapies which we
The following are examples of some of our
can present to those in need of medical help. And
regional activities.
we fully grasp the central role of our employees in all our endeavours.
The Americas The US Boehringer Ingelheim Cares Foundation
Our social activities encompass patients, neigh-
partners with AmeriCares in a programme to
bouring communities and society at large. l
provide free medical care to the uninsured working poor in the Greater Danbury area, Connecticut, using a mobile clinic. This allows physicians and nurses to voluntarily treat patients who might otherwise go without care. The mobile
30
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
corporate responsibility
unit also responds to emergencies, such as when
Tanzanian lab technician upskills in Germany
it was sent to Texas in September 2008 to treat victims of Hurricane Ike. In Mexico, one of our projects in 2008 was an ecological education programme for employees’ children – “Sembra uno arbol” – for reforesting areas around the company site. The aim was to generate environmental awareness and the need for protecting green spaces among the coming generation. Our highly successful project to provide healthier and more ecologically friendly
Ruth Ng’wananogu, a 30-year-old pharma
wood stoves to poor Indian communities also
ceutical technician from Muhimbili University
continued into its second phase.
of Health and Allied Sciences, Dar es Salaam, Tanzania, was in Germany in 2008 to study
Our Brazilian organisation’s charitable activities
basic technologies, procedures and equipment
included “Conectar”, a programme directed at
used in pharmaceutical development and pro-
disabled people with a view to helping them
duction at Boehringer Ingelheim. A diploma-
prepare to enter the jobs market, many for the
holder in pharmaceutical sciences, Ruth was
first time.
the first of a team of laboratory technicians to be trained at our German facilities to staff a
Asia, Australasia, Africa
new teaching and development laboratory at
Opened in 2005, the Boehringer Ingelheim
Muhimbili University in a project jointly imple-
Training and Facilitation Unit in Gaborone, Bot-
mented by the university, the German medical
swana, trains general practitioners, physicians,
aid organisation action medeor and the German
occupational health specialists, nurses, pharma-
(GTZ) Agency for Technical Cooperation. “When
cists, pharmacy technicians, medical store man-
I came to Germany, I had only little operational
agers and healthcare managers. In 2006, the first
experience. We in Tanzania are very skilled and
pharmacy student from Botswana commenced
eager to apply what we have learned. But our
studies at Rhodes University, Grahamstown,
opportunities are limited. My stay in Germany
South Africa, under a Botswana government
was very useful and I would clearly recommend
programme funded by Boehringer Ingelheim.
increasing such exchanges and activities.”
Beneficiaries are required to work in the public sector after completing their studies. Boehringer Ingelheim also helped the Government of Bot-
sity of Cape Town, South Africa, Boehringer
swana to build an Infectious Disease Care Clinic
Ingelheim provides full financial support for
(IDCC) at Gumare which opened in 2007.
medical students from disadvantaged backgrounds.
In South Africa, the company supports the “Turning the Tide” training and education pro-
Some 16,000 of Papua New Guinea’s 5.3 million
gramme for health professionals in HIV, which
inhabitants are infected with HIV, but few
has reached over 1,000 healthcare workers. The
infected people go to healthcare centres, so the
Boehringer Ingelheim Lung Institute at the Uni-
figures are likely to be vastly underestimated.
versity of Cape Town has been set up as a centre
With other pharmaceutical companies, the
of excellence to support clinical trials in infec-
Catholic AIDS Office, the Australasian Society
tious and respiratory diseases. Through its
for HIV Medicine (ASHM) and the government
Student Education Programme with the Univer-
of Papua New Guinea, Boehringer Ingelheim has
31
Caring for our neighbours – “We Care”
Help after the earthquake disaster in China
responsibility regarding the dangers of smoking. Our employees also volunteered in 2008 to give a day to making toys for children from marginalised communities and broken families under the programme of the “Soñar Despierto” foun dation. In 2008, our Portuguese arm continued its longstanding support for the humanitarian organisation Habitat for Humanity with our employees helping to build homes for those most in need.
Together with our local distribution partner, China National Pharmaceutical Group, the
In Turkey, Boehringer Ingelheim launched a
timely supply of Boehringer Ingelheim medi-
“Creative Libraries” project in 2008, which helps
cines to the people of the disaster-hit Sichuan
pupils at disadvantaged elementary schools to
region was ensured.
become socially responsible, and encourages their creativity by fostering reading and writing. Our employee volunteers oversee the work of
implemented a project to train healthcare workers
the libraries and the pupils involved go on to be
under the auspices of the Collaboration for
ambassadors to their peers. The initial three
Health in Papua New Guinea.
schemes in 2008 were in the Bursa region. l
The earthquake disaster that struck Sichuan Province in southwestern China in 2008 met with an immediate response from our Chinese country organisation and its employees. Cash donations were made through the collective initiatives of the R&D-based Pharmaceutical Association Committee (RDPAC), a non-profit and non-governmental organisation. In addition, a substantial amount of medicines for first aid treatment were provided.
Environmental protection and occupational safety
It is our conviction that commercial success is only possible if social and ecological factors are also taken into consideration.
Besides its well-established programmes, including the annual free healthcare day for local
This principle is highlighted in our Leitbild
people near the company’s Bogor site, Boehringer
(guiding corporate principles), in our worldwide
Ingelheim Indonesia in 2008 addressed the
“Principles for Safety, Quality and Environmental
issue of river health. In cooperation with the
Protection” and through our commitment to the
local authorities, company management and
principles of the “Responsible Care” initiative
employees devoted a day to cleaning up the
of the chemical industry. For many years now,
nearby Cibalok River.
we have been setting global standards for environmental protection and safe working con-
Europe
ditions, which have again been extended and
In Spain, Boehringer Ingelheim has joined forces
adapted in 2008. All our sites have set up appro-
with the town council of Sant Cugat, where the
priate management systems in an effort to
Spanish company is based, to provide education
guarantee continual improvement, beyond the
and health promotion and encourage collective
legal requirements, on the basis of identification
32
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
corporate responsibility
of goals and appropriate action programmes.
Saving the vultures in India
Regular audits conducted by Headquarters – 11 in 2008 – guarantee that standards are met and systems continue to function properly. Several current examples are provided below, showing how we put our policies into practice. Green chemistry The production of drug substances is inevitably associated with environmental impact in the form of waste and emissions. Reducing these to a minimum is generally in our own interest, as this usually brings considerable savings in costs at some later stage. The basis is laid during the development of a new drug substance. While we have taken this principle into account for many years, our mission was highlighted in 2008 when our US R&D site joined the “Green Chemistry Initiative” of the American Chemical Society. The aim of this initiative is to embed the sustainability factor in development even more firmly through detailed information, formal procedures and objectives. Handling highly potent compounds The handling of highly potent compounds is a crucial issue in the pharmaceutical industry. In a move to protect the health of our employees in the production plants, we stipulate and monitor compliance with the exposure limits for drug substances. Many sites have already installed technology that allows high-potency compounds to be handled without respiratory protection. At Ingelheim, Germany, alone EUR 5 million was invested in such systems in 2008. Implementation of new legal requirements The focus of our activities in 2008 was on implementing the recent legal requirements according to REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals). Following close examination of our supply chain, we have identified all the substances of significance to REACH registration at our European sites and have pre-registered these with the European Chemicals Agency within the specified timeline.
33
Environmental protection and occupational safety
For many years, diclofenac, a pain-killing drug, has been used for disease treatment in cattle in India. As carcasses of dead animals are left to vultures for traditional reasons, residues of the drug lead to intoxication and death of the birds. As a result, more than 99% of the indigenous species have already vanished from India. Feral dogs, rats and other vermin have taken over the role of the vultures and are reproducing without control, disseminating infectious diseases, like rabies, threatening animal and man. Two renowned non-governmental organisations* have convinced the Indian Government to ban the veterinary use of diclofenac and to promote the use of alternative drugs, non-toxic to vultures. Based on our expertise in pain management, Boehringer Ingelheim is supporting these initiatives with scientific advice and by providing data for the use of meloxicam in cattle. With this important help it will be possible to substitute diclofenac, considerably reducing the risk for vultures, thus reversing an ecological disaster and social harm in one of the most populous countries of the world. * The Bombay Natural History Society and The Royal Society for the Protection of Birds
We are also preparing for implementation of the
in the environment. We help allow the potential
UN’s Globally Harmonised System for the Clas-
risks to be assessed according to substantiated
sification and Labelling of Chemicals (GHS) that
scientific procedures. To this end, we prepare
is to be enacted in 2009 by the European Union.
environmental risk assessments for the registration of our medicines. Within the framework of
Medicinal products and the environment
a Swedish industrial initiative (see www.fass.se),
Our responsibility is not limited, however, to
Boehringer Ingelheim provides data on drug
production conditions or the obvious, rigorous
substances as well as on data of environmental
safety tests on our products for use in man.
significance. So far, no significant critical environmental effects have been identified for any of
The consumption of drugs, which are expelled
our drug substances.
from the patients’ bodies, ultimately leaves traces Reinforcing the safety culture A mere glance at our accident statistics shows that we have been improving continually. In the past
Work accidents
few years, however, we have begun to plateau. In order to implement improvements, it is now necessary to focus our activities on the reinforcement of our prevailing safety culture. The safety of our employees is our top priority; accordingly, large-scale initiatives to further improve the safety culture have been launched at our sites in Germany, the USA and Brazil. In 2008, the Board of Managing Directors also passed our Field Force Safety Policy, thus setting a clear signal that we will increase our efforts to
The key parameter for our performance in occupational safety is the accident rate in relation to hours worked. As the diagram shows, they
Work accidents have decreased slightly, but ultimately on a par Total work accidents: 242 (Fatality: 0) with previous Absence days:years. 3,323
improve safety for our field force which, at our company, along with production, reports the most frequent and most serious accidents. Expectations of our business partners We also expect our business partners – both suppliers and contract manufacturers – to meet
■ Frequency rate (= accidents x 1 million hours / total labour hours) ■ Severity rate (= lost labour days x 1 million hours / total labour hours)
certain requirements in terms of environmental protection and safety as well as in terms of social issues. A guideline stipulates that the suppliers 80
must complete a questionnaire and submit to a
70
Boehringer Ingelheim audit, where appropriate.
60
In 2008, internal training measures helped
5
50
advance implementation of this guideline.
4
40
3
Awards and certifications
2
In 2008, the environmental management system
1
at our site in Malgrat, Spain, received ISO 14001 2000
01
02
03
04
05
06
07
08
certification, following the path of our other two chemical sites in France and Italy. With the
34
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
corporate responsibility
certification of our industrial safety management
Less can be more – Focus on energy efficiency
system according to OSHA 18001, in addition to the previous certification of its quality and environmental management system, our site in Fornovo, Italy, achieved its goal of Total Quality Management. The site in Bogota, Colombia, was actually recognised several times for excellent environmental protection and safety performance and “Responsible Care” activities. For 2008, Boehringer Ingelheim Chemicals in Petersburg, Virginia, received a Governor’s Environmental Excellence award. No hazardous incidents Boehringer Ingelheim has implemented a policy
Our various projects focus on efficient use of
for crisis management with the aim to protect our employees, neighbours, customers, products,
energy and thus reduced CO emissions. The ² latest milestone is the chilled water accumula-
company assets and the environment from harm
tor inaugurated in October 2008 at our
or damage. Our proactive approach is designed
R&D and Biopharmaceuticals site in Biberach,
to primarily prevent incidents or keep them from
Germany. Here we took a completely new
escalating to critical levels. We have established
approach with a concept of chilled water accu-
global and local crisis plans and we are effectively
mulation, unique in the pharmaceutical indus-
prepared to respond promptly to any emergencies.
try. The chilled water accumulator is charged
There were no notifiable incidents within the
from the existing chillers at night or in low-load
Corporation in 2008.
periods. The more constant production of cold
Our goals
energy avoids 2,100 t of CO emissions a year. ² The EUR 3 million investment is offset by
Attention will continue to be focused on energy
savings in energy and water consumption as
efficiency, safety culture and social aspects of
well as less maintenance. Generating cold
supplier qualification in the years ahead. We
energy for controlled room conditions is one of
shall continue to invest in technologies in an
our most energy-demanding processes.
effort to protect employees handling highpotency compounds. In 2008, construction began which will expand the wastewater pre-treatment plant expansion at Boehringer Ingelheim Chemicals in Petersburg, Virginia, USA. This expansion will effectively double the organic treatment capacity of the plant while at the same time significantly improving the quality of the pre-treatment plant’s effluent to a level where water re-use may become a possibility. Facts and figures The graphs on the following pages show the figures for the last five years.
35
Environmental protection and occupational safety
Although we had already reached a high stand-
In this report we are only able to highlight part
ard in the past through technical or organisa
of the range of our environmental protection
tional measures, we have still been able to
and occupational safety activities in 2008. We
improve certain figures.
constantly deal with a number of further topics, which are described on our website at
We achieved significant reductions in:
www.boehringer-ingelheim.com/ehs.
• the CO² balance
• with respect to volatile organic carbon (VOC) emissions • water consumption • the chemical oxygen demand (COD) load The CO² balance improved, thanks essentially to the wood-fired power station in Ingelheim. VOC emissions were further reduced following commissioning of the thermal oxidiser for air pollution control in Malgrat de Mar, Spain, in 2007, in particular, while we recorded a reduction in water consumption following completion of the cooling circuits in Fornovo. Changes in the product portfolio and the production process, e. g. for dabigatran etexilate, resulted in a remarkable decrease of the chemical oxygen demand (COD) in the inflow to wastewater treatment. By inaugurating the expansion of the wastewater
Facts and figures
treatment plant in Ingelheim, we were addition-
The impact of our operations on the environ-
ally able to improve the efficiency and flexibility,
ment is described both in absolute figures and
to maintain the good COD degradation rates even
in relation to the production volume in the
for higher production volumes.
areas Pharma Chemicals, Pharmaceuticals Production, Biopharmaceuticals and Animal
We also improved with respect to: • energy consumption in relation
respective operations differs depending on the
to production
environmental impact. The reference year is
This is an effect mainly attributable to better capacity utilisation. With respect to special waste there has been a steep increase since 2006, while the recycling rate has dropped. This can be explained primarily by the change to disposal of slag from the wood-fired power station in Ingelheim. In the past, the slag was used for rock-filling in underground salt domes which is, according to official definition, regarded as recycling. Since 2006, the slag has been sent to landfill and therefore counts as special waste. The slag accounts for almost a quarter of the special waste disposed of, and around half of the special waste going to landfill.
36
Health, whereby the weight attached to the
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
2000. In 2008, our pharmaceuticals production site in France was divested and this site was not considered any more in the 2008 environmental performance figures. ¹2008 figure for COD inflow to WWTP at Ingelheim site based on calculation (assumption 98% degradation rate). ²Calculated CO² emissions attributable to our company car fleet (sales force): approximately
76,000 tonnes.
corporate responsibility
Water ■ Water consumption (in millions of m³) ■ Water consumption index (in %)
Energy ■ Energy consumption (in millions of gigajoules) ■ Energy consumption index (in %) 120
120
100
100
80
80
10
60
5
8
40
4
6
3
4
2
2
1 2000
01
02
03
04
05
06
07
08
2000
Wastewater — chemical oxygen demand (COD)¹ ■ COD load before treatment (in tonnes) ■ COD load after treatment (in tonnes) ■ COD load (after treatment) index (in %)
01
02
03
04
05
06
07
08
Disposed waste ■ Domestic waste (in tonnes) ■ Hazardous waste (in tonnes), incl. pharmaceutical waste ■ Disposed waste index (in %) ■ Recycling rate (in %) 100
120
80
100
60
80
10,000
40
60
8,000
20
30,000
6,000
22,500
4,000
15,000
2,000
7,500 2000
01
02
03
04
05
06
07
2000
08
Carbon dioxide (CO²)² ■ CO² indirect emissions (in 1,000 tonnes) ■ CO² direct emissions (in 1,000 tonnes) ■ CO² emissions index, direct emissions (in %) (excluding company car fleet)
01
02
03
04
05
06
07
08
Volatile organic carbon (VOC) ■ VOC emissions, non-halogenated (in tonnes) ■ VOC emissions, halogenated (in tonnes) ■ VOC emissions index (in %) 120
100
100
80
80
60
500
60
1,000
40
400
40
800
20
300
600
200
400
100
200 2000
01
02
03
37
04
05
06
07
08
Environmental protection and occupational safety
2000
01
02
03
04
05
06
07
08
sabrina löffel VTI Day is an excellent platform to present proposals and ideas.
38
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
corporate responsibility
Our people
stellter Akademiker und leitender Angestellter in der Chemischen Industrie) most preferred
Our guiding principles – Leitbild – and our vision “Value through Innovation” are the fundamental drivers of all our aspirations and actions.
employer survey of executives in the German chemical and pharmaceutical industries. In the poll, which covers questions on company strategy, corporate culture, employment conditions and personal satisfaction, we recorded the highest scores in all categories. In recognition of this sustained achievement, the VAA awarded Boehringer Ingelheim the first-ever “Cologne Chemicals Prize” (see also table “Awards 2008”).
Both challenge us to realise the potential and
Responding to external developments
enhance the strengths of our 41,300 dedicated
In the face of unprecedented challenges to the
people around the world who share an aspiration
global economy and intensified competition, we
for innovation. These basic principles also inspire
are paying close attention to enhancing our com-
us to create working environments, which ener-
pany’s and our people’s capabilities to effectively
gise our employees in their pursuit of innovation,
and successfully operate in an ever more inter
excellence, efficiency and fairness in everything
dependent and diverse business environment.
we do. The ambitious expectations we set ourselves in terms of standards and performance can only be attained by joining forces. Boehringer Ingelheim Our annual “Value through Innovation Day” is
“Value through Innovation Day”
but one example of the way in which we go about using our insights and creativity to find ways to build stimulating working environments. Every year in the spring, employees and management in our organisations come together to discuss and propose ways to realise related ideas and measures. Preferred employer The attractiveness of Boehringer Ingelheim as an employer of choice is widely acknowledged in highly regarded and independent surveys. This recognition reinforces our confidence in our distinctive corporate culture and working environment. The outcomes of these surveys underline our prime positives: our innovative and ambitious culture, our unique working environment, and our working relationships built on mutual respect and fairness. Special achievements were registered in 2008, when we succeeded for the seventh consecutive year in coming first in the VAA (Verband ange
39
Our people
At our headquarters in Ingelheim, Germany, the 2008 “Value through Innovation Day” focused on how to enhance coaching and development for our long-term individual and corporate success. In the spirit of the “Lead & Learn” initiative, our understanding of the way we work together, all employees and management engaged in interactive group discussions that generated a number of practical and beneficial recommendations. Many of them are already on the way to being implemented. Others are to follow soon.
As a corporation with employees in 138 affiliated companies worldwide, we have access to a highly effective means of identifying emerging customer needs, staying on top of the latest technology and scientific developments, as well as gaining from the viewpoints of our employees who represent a wealth of societies and backgrounds. Strengthening this network enables us to access manifold sources of knowledge sharing and knowledge
Top equality performance In the USA, Boehringer Ingelheim secured the top rating of 100 % in the Corporate Equality Index, an annual survey administered by the Human Rights Campaign Foundation. We thereby join 259 other major US businesses that have been given top marks for their equality performance.
generation for the benefit of all. In this context, developing language and technology skills, encouraging the acquisition of
international project work, global task-forcing,
intercultural knowledge and abilities, and
cross-border knowledge transfers as well as short
providing experience that gives a global outlook,
and long-term assignments abroad represent
are essential. Multidimensional, long-term
substantial constituents.
approaches are developed and introduced to foster lifelong learning, employability, diversity
Furthermore, in 2008, another cohort of 120 par-
management, enhancement of work-life balance,
ticipants completed our 14-month International
and the maintenance and enhancement of phys-
Management Development Program (IMDP), one
ical, mental and social well-being.
of the developmental approaches that provide a unique learning environment for management
Developing talent
potentials.
In our focus on developing talent, our philosophy underlines the active learning and develop-
Another forward-looking example for ensuring
ment of every employee as central to the success
and developing bench strength for the future
of our company. We are convinced that discover-
has again been set by our German operating unit.
ies and results are generated by people and we
In 2008, a noteworthy 673 individuals in 35
therefore continue to ensure that our employees
professions commenced vocational training
maintain and enhance their professional and
within the highly regarded and well-established
vocational capabilities. In our annual employee-
B oehringer Ingelheim apprenticeship pro-
supervisor dialogue, respective individual meas-
gramme.
ures that are mapped and jointly agreed form a central element of discussions.
Family-friendliness reconfirmed At all times, Boehringer Ingelheim has set great
The Boehringer Ingelheim Academy plays a sig-
importance on being a family-friendly company.
nificant role in realising our goals of lifelong
To continue to ensure that we are enabling our
learning and internationalisation. In 2008, a
employees a good work-life balance, we have
number of new or revised programmes were
subjected our personnel policy to a recurring
introduced to meet the changing needs of our
external audit.
business. The Academy offers are designed to give employees local and international options
The highly respected “berufundfamilie GmbH”
to address targeted developmental aspects in a
foundation conducted its initial audit and certi-
wide range of areas.
fication in 2005. Boehringer Ingelheim subjected its efforts to a re-auditing, and was awarded a
In our approach to developing leadership and
new certificate in 2008. Audits are monitored
specialist talent throughout our organisations,
yearly, with re-audits every three years.
40
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
corporate responsibility
The audits are a strategic management tool for systematically identifying and evaluating positive ways of combining working life with family life, with participating organisations agreeing to address targets for improvements by the next re-audit. The auditing scope includes working time, work organisation, work location, information and communication policies, management competence, personnel development, remuner ation structure and the value of services for families. l
Awards 2008 Country
Ranking
Brazil
Germany
Survey
20
100 Best Companies to Work For in Brazil (Great Place to Work Institute)
9
25 Best Companies for Executives to Work for in Brazil (Great Place to Work Institute)
1
“Bester Arbeitgeber” (Survey VAA) “Cologne Chemicals Prize” (VAA) Audit as family-friendly company
Italy
Special Award
Gender-equal opportunity employer (Assolombarda – Industrial Association)
Japan
Next-generation accreditation “KURUMIN” in recognition of NBI as a very family-friendly company in Japan
Mexico
Leader Companies in Mexico (HayGroup and HSM Editorial Group)
The Netherlands
Best werkgever Nederland (Best Employer Netherlands) (Corporate Research Foundation)
Spain
Family Award for Reconciliation Between Work and Family Life
UK
Best Places to Work (Sunday Times) 2 �
Best Places to Work in IT 2008 – Manufacturing & Engineering (Computer Weekly) NorthCoast 99 Award
USA
Best Places to Work for LGBT Equality – 100 % Corporate Equality Index Human Rights Campaign Top 50
41
Our people
Careers & the disABLED Magazine
Contents
} Personal passions – A beneficial balance to research } Our R&D strategy } Our R&D sites } Non-clinical research and development } From test tube to bioreactor – A seamless path for biopharmaceuticals } Clinical development } 2008 – The year of landmark trials } Bridge to academia
42
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Research & Development
dr heike neubauer “Painting is in many ways like research.”
44
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
research
&
development
Personal passions – A beneficial balance to research
Research and development in the pharmaceutical industry calls for imagination, determination, persistence and the crucial ability to work as an integral part of a team. New drugs take years, often a decade, from discovery of the initial molecule to a marketable medication. And throughout this long and sometimes challenging process researchers must stay alert, focused and flexible. So keeping fit, both mentally and physically, can make an important contribution to the final outcome of a research or development programme. At Boehringer Ingelheim, our company schemes provide support, but ultimately it is the employees themselves who find their own ways of staying fit and achieving a good work-life balance.
Dr Heike Neubauer, principal scientist at
For mental fitness, Dr Neubauer paints, some-
Boehringer Ingelheim’s Biberach research
thing she has loved doing since childhood. Today,
campus since spring 2003, is highly aware of the
her work is mainly in oil paint and she does much
need to stay in good physical and mental shape.
of her painting together with friends or in more
Indeed, she has a personal passion, painting,
formal painting groups. She has already had
which provides a very effective balance to her
work displayed in several exhibitions.
demanding daily research work. Her working day at Boehringer Ingelheim concentrates on identi-
“Painting, for me, is in many ways like research.
fying new molecules that potentially may become
You need technical knowledge how to do it, prac-
drugs for the treatment of metabolic diseases,
tice, persistence and creativity – some thinking
such as the current and fast-growing scourges of
outside the box. It helps you look again at things
obesity and diabetes.
with fresh eyes,” she notes. And some of her
45
Personal passions – A beneficial balance to research
paintings have taken years to finish. “As a
Increased research productivity has led to a well-
researcher, I’m familiar with working with
balanced pipeline with a substantial number of
persistence to achieve results.”
innovative first-in-class and best-in-class new molecular entities (NMEs) and a high share of
In her passion for painting, Dr Neubauer sees a
substances in late-phase development, strength-
similar challenge to that in her profession. Both
ening our competitive position.
make her want to learn, to improve, and to find new ways forward. Both pursuits also bring her
A continuous flow of innovative new chemical
into regular contact with very different groups of
entities (NCEs) has contributed substantially to
people who think very differently, too. She finds
our pipeline. Additionally, the discovery and
that this provokes new thoughts and ideas
development of new biological entities (NBEs)
beyond the world of pharmaceutical research
from our internal research and in-licensing con-
that may also help her in her work. ●
stitute another part of our strategy. The NBEs are co-developed and produced by our Biopharmaceuticals division in our facilities in Vienna,
Our R&D strategy
Austria, and Biberach, Germany.
Boehringer Ingelheim’s success is based on its own research and development, which continues to be the pre-eminent driver for innovative, new medicines to address unmet therapeutic need. Our constant quest for pharmaceutical innovation has resulted in successful ongoing collaborations as well as external partnerships with academic institutions, biopharmaceutical and start-up companies.
In order to improve efficiency and secure equal access to state-of-the-art technologies and informatics platforms across our R&D sites we have implemented global skill centers. To ensure the most efficient drug development our non-clinical development operates as a single internationally integrated organisation based on two major regional centers, one in the USA and one in Germany. Worldwide, we employ 3,700 scientists, technicians and support personnel in preclinical R&D. They are complemented by about 2,800 clinical monitors, statisticians and data managers in clinical development and medical departments. In-licensing and partnering In-licensing and partnering activities constitute essential elements of Boehringer Ingelheim’s R&D strategy. Together with our partners we in 2008 accomplished a series of important success milestones in our ongoing collaborations. In order to forge new partnerships, we are prepared to adopt creative deal structures. An example is
Our R&D direction
the acquisition of San Diego-based Actimis Phar-
Our R&D strategy focuses on seven major thera-
maceuticals Inc. This transaction will occur
peutic areas: central nervous system (CNS)
through a structured buyout in which Boehringer
diseases, cardiovascular diseases, immunology/
Ingelheim will acquire shares of Actimis depend-
inflammation, metabolic diseases, oncology,
ing on the achievement of several successive
respiratory diseases and viral diseases.
milestones with Actimis’ leading asthma com-
46
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
research
&
development
pound AP768. If AP768, currently in phase I
Basic research partnerships
clinical development, is successfully advanced
The bridge between our R&D researchers and
into a phase III, Boehringer Ingelheim will own
academia is reinforced by the strong link to the
100 % of Actimis shares. The compound AP768
renowned Research Institute of Molecular
interacts with CRTH2, a novel target for asthma
Pathology (IMP) in Vienna. IMP scientists from
and allergic rhinitis, which has the potential
30 different countries are at the forefront of
to be more effective than currently marketed
discovery, defining fundamental mechanisms in
leukotriene receptor antagonists.
areas ranging from cellular proliferation to cancer and neurobiology. The collaboration
We also continue to expand our R&D pro-
between the IMP and the Institute of Molecular
grammes in biopharmaceuticals through col-
Biotechnology of the Austrian Academy of
laborative research and license agreements. Thus,
Science (IMBA) has given an additional dimen-
we have entered into a partnership with Evec Inc.,
sion to our academic network. ●
a Japanese biotechnology company, for one of its fully human therapeutic antibody programmes. Based on the agreement, Boehringer Ingelheim will obtain worldwide exclusive development and commercialisation rights for the complete programme. This collaboration is considered to be one of the first compound-related license agreements between a Japanese biotech venture and a multinational pharmaceutical company outside Asia.
Oncology
Human tumour cells after 24 hours of treatment with an anti-mitotic substance (immunofluorescence stain). The picture shows faulty cell spindles (green) and fragmented DNA (red). Link to research in oncology: http://www.boehringer-ingelheim.com/ corporate/research/index.asp.
47
Our R&D strategy
Our R&D sites
In accordance with our R&D strategy we carry out drug discovery and development in seven therapeutic areas at four major R&D sites and three smaller specialised sites. These R&D sites maintain responsibility and accountability for their therapeutic areas with regard to output and quality of novel drug candidates.
Major R&D sites and main R&D areas Ridgefield, USA
Laval, Canada
• Cardiovascular (chronic heart • Virology (acute and chronic failure, atherosclerosis, hypertension) viral diseases, HIV, hepatitis C • Immunology and inflammation virus) (rheumatoid arthritis, psoriasis, multiple sclerosis) • Non-clinical drug development
48
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Biberach and Ingelheim, Germany • Central nervous system – CNS (Alzheimer’s disease, Parkinson’s disease, chronic pain, migraine) • Metabolism (type 2 diabetes, obesity, dyslipidaemia) • Respiratory (COPD, asthma, chronic bronchitis, idiopathic pulmonary fibrosis) • Non-clinical drug development
research
&
development
• Ingelheim Biberach • • Vienna • Milan
• Laval • Ridgefield
• Kobe
• Buenos Aires
Smaller, specialised R&D sites Vienna, Austria
Buenos Aires, Argentina
Milan, Italy
Kobe, Japan
• Oncology (signal transduction, cell cycle therapeutic proteins)
Center for non-clinical development: • Drug formulation, manufacturing of medication for clinical trials
Center for chemical synthesis: • Synthesis in exploratory and lead optimisation projects
Center for molecular biology and non-clinical drug development: • International drug discovery activities • Early drug formulation • Specific pharmacokinetic investigations
49
Our R&D sites
dr reiner meyer “For me, research means scope to try out new ideas.”
50
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
research&& development development research
Non-clinical research and development
The unravelling of the human genome has accelerated the identification of the faulty biochemical circuitry that underlies the prolifera-
Boehringer Ingelheim successfully rises to the challenges of discovery and development to bring innovative and safe drugs to patients.
The focus of our drug discovery is on several
Metabolic diseases
targets, which we try to attack with small mole-
tion, invasion and metastasis of cancerous cells in the body. These insights provide important clues to new drug targets and the early identification of patients whose cancers are most likely to respond to novel drugs, a process known as biomarker-guided therapy.
novel mechanisms to interfere with cancer Our broad engagement in preclinical research in
cules and biopharmaceuticals. The newest
metabolic diseases is focused on type 2 diabetes,
biological entity (NBE) molecules (human mono-
obesity and dyslipidemia. The research activities
clonal antibodies) from Boehringer Ingelheim
in the field of type 2 diabetes concentrate on sev-
trigger the death of tumour cells, or inhibit
eral new approaches to delay disease progression.
uncontrolled cell growth, whereas our current
Furthermore, new projects have been initiated
small molecules prevent the unimpeded prolif-
with the potential to target other cardiovascular
eration of cancer cells.
risk factors in addition to their glucose-lowering effect, thus allowing simultaneous intervention
Central nervous system (CNS) diseases
in various risk factors of the metabolic syndrome,
Our research in CNS diseases addresses four
such as hyperglycaemia, dyslipidaemia, obesity
major indication areas characterised by a high
and hypertension. In the future, our major
unmet medical need and a heavy burden for
emphasis will be on dyslipidemia and athero
patients and caregivers, especially in an ageing
sclerosis targets.
population. These include the most prevalent neurodegenerative disorders, such as Alzheimer’s
In 2008, we started pre-development activities
disease and Parkinson’s disease, as well as
with another compound based on a novel
chronic pain and migraine. Our major goal in
principle to target the metabolic syndrome. With
Alzheimer’s disease and Parkinson‘s disease is to
the University of Dresden and the Max-Planck-
interfere with the processes underlying the
Institute, Dresden, Germany, we continued our
continuous degeneration of nerve cells in these
collaboration to identify and validate novel
devastating disorders, concentrating on targets
targets in metabolic diseases. Promising initial
established by histopathological and genetic
data have been obtained.
evidence.
Oncology
In chronic pain we focus on new molecular tar-
Boehringer Ingelheim is actively developing
gets involved in pain transduction pathways and
small molecules and biopharmaceuticals as novel
validated in neuropathic and inflammatory pain
drugs for combating cancer. With front-line re-
models. Our endeavours have resulted in two
search and development projects the company
development compounds for the treatment of
aims to fill therapeutic gaps by offering treat-
chronic pain, both compounds having a different
ments that improve survival and enhance the
but complementary efficacy profile in preclinical
quality of life of cancer patients.
models.
51
Non-clinical research and development
To complement our activities in the indication
and to improve treatment of atherosclerosis.
areas pain and neurodegeneration, we have
These efforts have resulted in the identification
joined an academia/university consortium
of several novel approaches for cardiac and renal
Innovative Medicines Initiative (IMI), created by
protection and treatment of atherosclerosis. In
the European Federation of Pharmaceutical
2008, dabigatran etexilate (pradaxa®) from
Industries and Associations (EFPIA) and the EU.
Boehringer Ingelheim was the first oral anti coagulant to achieve approval for more than 50
Respiratory diseases
years. It is a first-in-class direct oral thrombin
The key goal in our research is to extend our
inhibitor. Following dabigatran etexilate, we suc-
portfolio in chronic obstructive pulmonary
ceeded in nominating another two compounds
disease (COPD) to directly treat the underlying
for development, targeting alternative mecha-
inflammation and the related tissue remodelling
nisms for the treatment of thrombo-embolic
processes.
diseases.
To prevent or delay tissue remodelling processes
Viral diseases
we target lung growth factors. Two first-in-class
Drug discovery and development efforts in virol-
mechanisms focused on mucous hyperplasia and
ogy are focused on the treatment of HIV and
fibrosis are being tested clinically. Beyond COPD,
hepatitis C virus infection in order to improve
such new mechanisms have a therapeutic poten-
existing therapy by providing patients with safe
tial in idiopathic pulmonary fibrosis (IPF) and in
and more effective antiviral drugs.
severe asthma, where mucous plugging is considered the main cause of death.
Thus, we are pursuing a number of promising targets for direct-acting antivirals that will inhibit
For severely asthmatic patients, our research
the replication of the virus within the infected
goals focus on new targets to overcome steroid
cell by interfering with the virally encoded
resistance and to replace or reduce the doses of
enzymes involved. Several compounds from
inhaled steroids by providing better tolerated
these projects are being pursued in pre-clinical
anti-inflammatory therapy superior to leuko
research and offer promise as future development
triene receptor antagonists.
candidates and ultimate treatments for patients.
In this context, a new mechanism effective in
Immunology & inflammation
asthma and allergic rhinitis was taken up in early
Our drug discovery focuses on mechanistic
discovery phase; moreover, several additional
understanding of rheumatoid arthritis, multiple
screening programmes were successfully
sclerosis and psoriasis disease processes in order
completed.
to identify novel targets for developing drug can-
An additional step to extend our development
we in-licensed two potential targets from the
didates. For the treatment of rheumatoid arthritis portfolio was achieved when in-licensing the
collaboration with Galapagos NV / BioFocus DPI.
compound AP768 from Actimis Pharmaceuticals
Based on these new approaches, we advanced
for treatment of rhinitis and asthma.
two compounds into preclinical/clinical development, one inhibiting the invasion of inflam-
Cardiovascular diseases In our research activities we strive to identify novel approaches for the treatment of risk factors, such as hypertension, to follow disease modifying therapeutic strategies, for instance in heart failure, providing cardiac and renal protection,
52
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
matory cells into inflamed tissue and joints. l
research&& development development research
From test tube to bioreactor –
manufacturing cell lines and establishes fermen-
A seamless path for biopharmaceuticals
tation and downstream processes. Once a project passes the gate to pre-clinical development, bio
Capitalising on our scientific and technical capabilities in drug discovery and in the development and manufacturing of biopharma ceuticals, Boehringer Ingelheim is well positioned to develop next-generation therapeutic proteins. Across therapeutic areas, we have built a broad new biological entity (NBE) project portfolio that largely, though not exclusively, comprises monoclonal antibody (MAb) drug candidates. A special challenge in MAb drug discovery
pharmaceutical manufacturing scales up and optimises the production process to ensure a seamless transition to clinical trial and market supply. ●
Clinical development
Continuous initiatives to increase R&D productivity have resulted in a wellbalanced pipeline showing a substantial number of new molecule entities and a high share of compounds in late phase development.
is the need to integrate expertise in diseasespecific pharmacology and in NBE-specific
Metabolic diseases
biotechnologies.
In our therapeutic area metabolic diseases the research teams have been focused on the
At Boehringer Ingelheim, screening to identify
discovery and development of oral anti-diabetic
high-affinity human MAbs for all therapeutic
treatments targeting new principles, such as
areas is the task of a single, specialised team
inhibition of dipeptidylpeptidase-4 (DPP-4) and
applying multiple technologies in parallel,
of sodium-dependent glucosetransporter-2
including antibody phage display and transgenic
(SGLT-2). These compounds reflect the dedica-
mice carrying human antibody genes. In addi-
tion of Boehringer Ingelheim to harnessing the
tion, access to camelide nanobodies, the smallest
most advanced science to efficiently control type
antibody-like protein domains created by nature,
2 diabetes and its often serious consequences.
is available through collaborative research. At each research site, dedicated NBE technology
Our compound bi 1356 (intended brand name
groups take over the screening hits, engineer
ondero®), a DPP-4 inhibitor, has entered a
protein formats and expression systems, and
broad phase III study programme. By the end
produce and purify pilot quantities of MAbs.
of 2008, the recruitment of more than 4,000
Finally, pharmacologists in the respective thera-
randomised patients was successfully achieved
peutic area profile the drug candidates in models
ahead of plan. bi 1356 is studied in monotherapy,
of human disease. Early on, NBE experts from
as well as in combination with established
the development disciplines, such as non-clinical
therapies, such as metformin, a sulfonylurea, or
drug safety and pharmacokinetics, are integrated
a thiazolidindione. In addition, bi 1356 is under-
into the project teams, and biopharmaceutical
going a large two-year study comparing bi 1356
process development initiates generation of
to glimepiride.
53
Clinical development
Our second principle under development in
Boehringer Ingelheim is broadening its cell-cycle
type 2 diabetes is targeting therapeutic glucose
kinase inhibitor portfolio by investigating poten-
elimination. With proof-of-principle and good
tially first-in-class compounds, so-called PLK-1
tolerability established for our SGLT-2 inhibitors
inhibitors. bi 6727, a PLK-1 (Polo-like-kinase-1)
in short term phase II clinical studies during the
inhibitor, is blocking the cell cycle, and thereby
year, several studies of 12 weeks duration with
cell division and has shown encouraging results
mono and combination therapy have been
in a phase I clinical trial in patients with ad-
initiated.
vanced tumours who have failed to respond to other treatments. The compound is now in phase
Oncology
II clinical development in solid tumours and
In the therapeutic area oncology, our portfolio of
haematological cancers.
compounds matured significantly in 2008. One of our most advanced compounds, bibw 2992
As planned, another cell-cycle kinase inhibitor
(intended brand name tovok®), is a novel repre-
with, however, different mode of action (mitotic
sentative of the new generation of tyrosine ki-
kinase inhibitor) has already entered clinical
nase inhibitors. It is an irreversible inhibitor of
phase I.
both EGFR and HER2. Promising phase II data showed that advanced non-small-cell lung can-
Central nervous system diseases
cer (NSCLC) patients treated with bibw 2992
With the importance of non-motor symptoms
experienced a high rate of disease control (87 %)
in Parkinson’s disease widely recognised, the
and promising overall response rate (50 %). The
results of a dedicated randomised placebo-con-
compound has now entered phase III clinical
trolled clinical trial of sifrol® (pramipexole) in
trial in the most frequent form of non-small-cell
alleviating depressive symptoms associated with
lung cancer (NSCLC). As bibw 2992 also inter-
Parkinson’s disease have become available: the
feres with HER2, a phase II programme in
six-month placebo-controlled study established
patients with breast cancer failing trastuzumab
for the first time significant beneficial effects of
treatment is ongoing.
pramipexole on depressive symptoms in patients with Parkinson’s disease.
The second principle, which has concluded phase II and is entering phase III, is bibf 1120
The worldwide phase III programme for
(intended brand name vargatef®), a novel triple
pramipexole extended release has been success-
angiokinase inhibitor. The substance simultan
fully brought forward both in patients with early
eously inhibits three growth factors and recep-
and with advanced Parkinson’s disease. The
tors (VEGFR, PDGFR and FGFR) that play an
pivotal phase III studies established clinical
important role in angiogenesis. Promising effi-
efficacy and confirmed the expected good toler-
cacy and tolerability data have been reported
ability. It was also demonstrated that almost all
from a phase II study in patients with advanced
patients can be switched smoothly and without
non-small cell lung cancer (NSCLC), when
dose adjustment from sifrol® to its extended
bibf 1120 was administered as monotherapy.
release formulation. Market authorisation is
Two clinical phase III pivotal trials with 1,300
expected for 2009.
patients were initiated around the world by the end of 2008.
In one study, it was shown that duloxetine (cymbalta®/xeristar®) is not only effective
bibf 1120 (vargatef®) is also being investigated
for the treatment of depression, but also in the
in first-line treatment of ovarian cancer with a
prevention of recurrence of depression in
1,200 patient phase III study in pre-initiation, as
patients who have shown initial treatment
well as in prostate cancer and colorectal cancer.
response.
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Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
research&& development development research
Flibanserin is an investigational compound
inhaler respimat® has been successfully com-
in clinical development for the treatment of pre-
pleted and has led to a submission for registra-
menopausal women suffering from hypoactive
tion shortly after close-out of the pivotal study.
sexual desire disorder (HSDD). This is a common condition affecting up to one in ten women and
Cardiovascular diseases
can frequently cause substantial distress and
pradaxa® (dabigatran etexilate), our orally
interpersonal difficulties.
available anticoagulant which acts through
bouquet®, an extensive phase III trial pro-
registration in Europe and in an increasing
gramme involving approximately 5,000 women,
number of countries outside of Europe. Accord-
has been completed in North America and a cor-
ing to the front-runner programme in clinical
direct thrombin inhibition, has obtained first
responding study in Europe has fully recruited.
development, pradaxa® is approved to prevent
We are confident that with the integration of the
venous thrombo-embolic events after elective
European study results we will have a promising
total hip or knee replacement and needs no
submission dossier for Europe and the USA.
regular monitoring of thrombocytes or coagulation parameters.
Respiratory diseases From our earlier pipeline the long-acting inhaled
In addition to the ongoing phase III programmes
beta-agonist bi 1744 has shown conclusive posi-
in surgical and non-surgical conditions, includ-
tive clinical phase II results which are the robust
ing long-term prevention of venous thrombo-
basis for a large phase III programme for bi 1744
embolism and stroke prevention in atrial fibril-
as a maintenance treatment of chronic obstruc-
lation, we initiated a large phase II study for the
tive pulmonary diseases (COPD). This pro-
secondary prevention of acute coronary
gramme has been initiated internationally. The
syndrome (re-deem™), which has already in-
bi 1744 mono compound development is com-
cluded some 1,000 patients.
plemented by a phase II programme for its combination with spiriva® (tiotropium), our
In total our re-volution® trial programme has
leading long-acting anticholinergic medication
recruited more than 30,000 patients. The largest
for COPD. With the good ongoing progress we
trial re-ly® for stroke prevention in patients
expect the combination programme to enter
with atrial fibrillation has rapidly included more
phase III in 2009.
than 18,000 patients and will have last patient
The worldwide proof-of-concept study of our
quarter of 2009, with results published in the
new anti-angiogenesis molecule in development
autumn.
out several months ahead of plan in the first
for the treatment of idiopathic pulmonary fibrosis was initiated and is recruiting well ahead of
The studies for the treatment of acute venous
schedule.
thrombo-embolism (VTE) – re-cover™ – and for secondary long-term prevention of VTE in
In the USA, the spiriva® respimat® new drug
patients at risk – re-medy™ – are running in
application (NDA) has gone through the first
parallel to re-ly® and will after the review of
Food and Drug Administration (FDA) review
stroke prevention in atrial fibrillation, provide
cycle.
additional submission opportunities.
Other respiratory programmes have also seen
Due to the need of results from still ongoing
relevant progress. In the USA, the clinical
studies in the USA, the submission of pradaxa®
development of combivent® (ipratropium and
for the primary prevention of VTE has been
salbutamol) in our innovative propellant-free
postponed.
55
Clinical development
For micardis® (telmisartan) the studies to inves-
2008 – The year of landmark trials
tigate the combination product with the calciumantagonist amlodipine in severely hypertensive patients who are not sufficiently treated with the mono-compounds have been successfully concluded, with submission planned in the USA in the first quarter of 2009. The European longerterm follow-up studies will be completed in time to support a European submission later in 2009. Viral diseases The large pivotal clinical phase III trial for the new once-daily extended release form of vir amune®, our non-nucleoside reverse transcriptase inhibitor (NNRTI), has completed patient recruitment, and is progressing smoothly towards one-year follow-up at the end of 2009. We aim to establish advanced convenience and good safety combined with reliable efficacy for worldwide registration. For two new hepatitis C compounds with different but potentially complementary mechanisms, we established proof of potent antiviral efficacy when given to infected patients for up to two weeks. Both compounds will move forward into
Boehringer Ingelheim is proud to have provided the medical community with the results from five landmark trials – all in 2008. These results enhance medical knowledge and management of three diseases, which are common causes of death: stroke, chronic obstructive pulmonary disease (COPD) and heart disease. Stroke Stroke is a debilitating disease that puts a great burden on the lives of patients and their families.
phase II and phase IIb. Urological diseases For flomax® (tamsulosin), our leading treatment
ecass 3™, which included 821 patients, investi-
for the symptoms of benign prostate hyperplasia,
gated whether the efficacy and safety of alteplase
we have received agreement with the Food and
(actilyse®) were maintained up to 1.5 hours be-
Drug Administration (FDA) to perform a paedi-
yond the standard 3-hour time window. The
atric development programme in children with
study results, published by the New England
neurogenic bladder dysfunction. Since these
Journal of Medicine, showed that patients treated
children are severely ill and normally have the
with alteplase in this extended time window had
congenital malformation spina bifida, recruit-
a 34 % improvement in the odds of having a
ment into such clinical trials is extremely difficult
favourable outcome versus placebo. Internation-
and often unsuccessful. Nevertheless, by the end
al stroke experts agree that this new study in the
of 2008 we had successfully completed recruit-
management of acute stroke has set a landmark,
ment into all required trials and will thus be able
as ecass 3™ has demonstrated that stroke can be
to fulfil the commitments for this paediatric pro-
safely and effectively managed also in the
gramme in time for submission. ●
3–4.5-hour treatment window. While early treatment remains the cornerstone of acute stroke therapy, many patients who are unable to reach a stroke centre within three hours may benefit in the future from these positive findings.
56
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
research&& development development research
The prevention of stroke was specifically investi-
from 37 countries. The results were published in
gated in profess® and stroke was also included
the New England Journal of Medicine. The trial
in the primary endpoint of ontarget™ and
compared spiriva® (tiotropium) versus placebo,
transcend®. profess®, the world’s largest trial
allowing all patients throughout the trial to use
in recurrent stroke prevention, included more
all prescribed respiratory medications other than
than 20,000 patients. The study compared
inhaled anticholinergics.
aggrenox® (extended release dipyridamole + ASA) with clopidogrel, while also analysing
While in the trial, spiriva® (tiotropium) did not
whether telmisartan, on top of other standard
alter the rate of decline in lung function versus
therapy, would further reduce the risk of recur-
the control groups, it demonstrated that spiriva®
rent stroke when compared with placebo. These
(tiotropium) impacts the clinical course of COPD
study results too were published in the New Eng-
over the long term through sustained improve-
land Journal of Medicine. In the two antiplatelet
ments in lung function and quality of life. In
regimens the patients had a comparable risk for
addition, tiotropium significantly reduced the
stroke, as well as for myocardial infarction or
risk of exacerbations and severe exacerbations
vascular death.
leading to hospitalisation. To date, no medication has been conclusively shown to reverse the decline in lung function. In uplift®, the rate of decline of lung function was the lowest of any
Hypertension is one of the most important risk
large-scale COPD trial, signifying that patients
factors for recurrent stroke, and reducing blood
today are treated more effectively than in the past.
pressure is a key goal in stroke prevention. In the
Despite this better treatment, tiotropium resulted
telmisartan arm of profess®, the duration of the
in significant and patient-relevant improvements
study was not considered long enough to reliably
of many long-term outcome parameters.
evaluate whether blood pressure lowering is of
Throughout the four-year trial period, patients in
clinical value in post-stroke patients. However, in
the tiotropium group consistently reported a
an analysis conducted after the end of the trial, it
better health-related quality of life than at study
was demonstrated that telmisartan did have a
initiation.
significant protective effect emerging six months after the initiation of treatment.
In addition, an increase in survival was observed under tiotropium, as well as a reduction in
Chronic obstructive pulmonary disease (COPD)
respiratory and cardiac morbidity, which conclu-
COPD is a progressive yet treatable disease that
sively reaffirms the favourable safety profile of
restricts patients’ lives over time and is a major
tiotropium. uplift® demonstrated that tiotro-
cause of death and disability throughout the
pium can impact the clinical course of COPD
world. The latest World Health Organization
over the long term through sustained improve-
(WHO) figures estimate that 210 million people
ments in lung function, quality of life, exacerba-
are currently living with COPD and more than
tions and improved survival.
three million people died from the disease in 2005 – more than breast cancer and diabetes
Cardiovascular protection
combined.
Cardiovascular (CV) diseases remain the primary cause of death in the industrialised world.
uplift® is one of the largest COPD trials ever
In the ontarget™ trial programme, the efficacy
undertaken, involving nearly 6,000 patients
of telmisartan in the reduction of CV events
57
2008 – The year of landmark trials
was studied in more than 30,000 patients. In
transcend® also demonstrated that patients are
ontarget™, published in the New England
treated better today than ten years ago. For
Journal of Medicine, the angiotensin II receptor
instance, the percentage of patients experiencing
blocker (ARB) telmisartan (micardis®) matched
a myocardial infarction was about three times
the cardiovascular protection of the current gold
lower in transcend® than in the hope trial
standard ramipril, an angiotensin-converting
placebo groups. Despite this much improved
enzyme (ACE) inhibitor, in protecting against the
standard of care, telmisartan treatment resulted
risk of CV death, myocardial infarction, stroke
in a significant risk reduction in CV death,
and hospitalisation for congestive heart failure
myocardial infarction and stroke, a result that is
in high risk patients. The results also provided
clinically meaningful for patients at high cardio-
another important answer to an open question,
vascular risk.
whether the combination of an ARB and an ACE inhibitor, if added to best standard of care, does
ontarget™, together with its sister trial
not provide further protective benefit. Impor-
transcend®, confirm, on top of best standard of
tantly, ontarget™ showed that patients tolerate
care, telmisartan’s long-term protective benefits
telmisartan significantly better than the ACE
with regard to cardiovascular events and its
inhibitor ramipril, which supports a better
excellent tolerability profile. ●
adherence of the patients to their medication and is crucial for the effective long-term prevention of serious cardiovascular events.
The transcend® trial involved almost 6,000 patients who did not tolerate an ACE inhibitor due to side effects and was published in The Lancet. This ambitious trial had predefined a four-fold composite primary endpoint consisting of CV death, myocardial infarction, stroke and hospitalisation for congestive heart failure. For this combined primary endpoint, transcend® showed a risk reduction of 8 % for telmisartan, although this was not statistically significant. The main secondary endpoint (CV death, myocardial infarction and stroke) was similar to the primary endpoint of the hope trial, the first trial demonstrating a reduction of CV events by inhib-
Bridge to academia
The bridge between our R&D researchers and academia is built by the strong link to the renowned Research Institute of Molecular Pathology (IMP) in Vienna. We are also engaged in several successful ongoing partnerships with leading academic institutions.
iting the angiotensin system. A statistically significant 13 % reduction was demonstrated for
PREVENT-it maps cardiovascular disease
telmisartan in this endpoint. In the control group
on a broad front
there was extensive use of CV drugs; for some CV
In the search for new approaches to preventing
drug classes (diuretics, calcium channel blockers,
and treating cardiovascular disease, the leading
beta-blockers) there was substantially more use
cause of death in the developed world, the Clinic
in the control group than in the telmisartan
and Medical Department of Johannes Gutenberg
group, which probably impacted the outcome
University, Mainz, supported by Boehringer
and potentially blurred some of the benefits of
Ingelheim, is conducting a broad-scope, long-
telmisartan.
term clinical study.
58
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
research&& development development research
The seven-year study – PREVENT-it (PRoteom-
physical condition, lipids and blood glucose, as
ics, genomics and Vascular ENdoThelial dys-
well as DNA and protein patterns. Using ultra-
function) – also known as The Gutenberg Heart
sound technology, the investigators measure
Study, will involve 17,000 people from the
vasodilatory and endothelial functions to detect
German city of Mainz and its environs. Recruit-
early damage to blood vessels.
ment is among the age group 35–75. Baseline examinations take place in the first 2.5 years,
IMP – The life science think-tank
with follow-up examination after 4.5 years. The
The Research Institute of Molecular Pathology
primary objective of PREVENT-it is on achieving
(IMP), the prestigious basic research institute,
an improved risk assessment of cardiovascular
which celebrated its 20th anniversary in 2008, is
disease.
firmly committed to uncovering fundamental molecular and cellular mechanisms underlying
A score system for cardiovascular risk stratifica-
complex biological phenomena.
tion will be established, taking into account psychosocial, environmental and lifestyle factors,
A Boehringer Ingelheim research institute, the
the relevance of sub-clinical disease, observable
IMP, based in Vienna, Austria, has made great
characteristics and genetic variability. New target
strides since it started out as an oncology-focused
molecules for an improved medical treatment of
institution. Today, its curiosity-driven research
cardiovascular and metabolic diseases will also
programmes are conducted by 15 independent
be identified and validated. New biomarkers will
groups spanning the molecular processes in the
be identified, which could lead to early diagnosis
development, functioning and disease mecha-
and increased predictability of cardiovascular
nisms of all living beings. Main areas of research
diseases.
include developmental biology, cell cycle control, cell differentiation, oncogenesis, chromosome
This is to be achieved with the means of a bio-
biology and bioinformatics.
databank: population data is collected on general Boehringer Ingelheim can benefit both from targets the IMP researchers discover for new drugs Professor Stefan Blankenberg, University Clinic Mainz, Germany
and from the bridge the institute is building to academia worldwide. The IMP’s 200 scientists are drawn from 30 countries. IMP research has, for instance, recently led to Boehringer Ingelheim developing a new cancer drug, now undergoing phase II clinical trials, that involves a wholly new mode of action. The IMP cooperates closely with the Austrian Academy of Sciences, mainly through its Institute for Molecular Biotechnology – a partner
Study leader, Professor Stefan Blankenberg, University Clinic, Mainz: “We expect significant findings about the prevention and treatment of cardiovascular and metabolic diseases and hope that they will improve predictability as well as optimise the clinical development of new drugs.”
59
Bridge to academia
and neighbour of the IMP. Dr Barry Dickson, the IMP Director, says: “IMP has developed into one of the most dynamic innovative life science centres in Europe. We can attract the best people in the world and help them realise their full potential. And it’s also great to see our researchers taking top positions when they move on.” ●
Contents
} Courage and persistency in fighting COPD } Highlights Branded Prescription Medicines } Highlights Generic Prescription Medicines } Highlights Consumer Health Care (CHC) } actilyse® – A 20-year strike against stroke } Biopharmaceuticals } Pharmaceuticals Production } Pharma Chemicals } Manufacturing excellence in our centre for global animal health vaccines } My lion queen leaps again! } Highlights Animal Health } Samples of the product portfolio
Net sales 2008 in millions of EUR Change in euro terms (change in local currencies) Boehringer Ingelheim Corporation 11,595 + 5.9 % (+ 9.5 %)
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Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Our business
Human Pharmaceuticals 11,128 + 5.5 % (+ 9.1 %)
Prescription Medicines 9,111 + 5.2 % (+ 9.3 %)
Branded Prescription 8,662 Medicines + 6.9 % (+ 10.9 %)
Generic Prescription 449 Medicines - 19.7 % (- 13.9 %) Consumer Health Care
1,190 + 4.3 % (+ 5.4 %)
Industrial Customer
819
Biopharmaceuticals
+ 10.8 % (+ 12.3 %)
569 + 22.8 % (+ 22.8 %)
Pharmaceuticals Production 121 - 7.4 % (- 2.8 %) Pharma Chemicals
Animal Health
467 + 14.4 % (+ 19.5 %)
129 - 11.2 % (- 9.0 %)
sebastião francelino “The start of the COPD treatment was the turning point in my life.”
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Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
human pharmaceuticals
Courage and persistency in fighting COPD
Sebastião Francelino, a 68-year-old retired Brazilian salesman, who loves life and driving, visited most of his vast country when he was working. “This is what I miss most. COPD took it from me,” says Tião, as he prefers to be called. A native of Rio de Janeiro who, from his condo balcony in the city’s traditional Penha district, can see the famous Guanabara Bay. Tião tells of how hard it was to quit smoking, an addiction that caused his chronic obstructive pulmonary disease (COPD), an illness currently affecting over 5.5 million Brazilians. A smoker from just 13 years of age, Tião suffered his first pulmonary crisis at the age of 55. “I was extremely tired and short of breath and had to be hospitalised. I already had COPD then, but was only diagnosed at the age of 59 years,” he explains. Frequently, during his business trips, he had had to rush to the closest point where he could get emergency assistance with breathing. The symptoms worsened, and only six years later, after he was finally diagnosed correctly, he started to receive the appropriate treatment.
The start of his COPD treatment at Hospital Uni-
Maria Helena and walk my little dog Luke Sky-
versitário Clementino Fraga was a turning point
walker. Some day, I will take Maria Helena up to
in Tião’s life. He was the first patient to obtain
the Christ the Redeemer statue in Rio and the
treatment free of charge from the Rio de Janeiro
Sugar Loaf, two of Rio’s most famous sights, and
State public health system. This led him to
take many photos for posterity.”
successfully manage his life with COPD and regain some of the freedom to do things that he
Realising the difficulties COPD sufferers face, to
had missed. Very much a family man and a fan of
fight smoking and help other COPD sufferers,
romantic songs, he says: “I want to go back trav-
Tião founded, and is still chairman of, the Asso-
elling, spend more quality time with my wife
ciação Fluminense de Portadores de DPOC (Rio’s
63
Courage and persistency in fighting COPD
COPD patients’ association). With four children,
spiriva®
six grandchildren and one great-grandchild, Tião wants his descendents to clearly understand the dangers of cigarettes and never surrender to smoking. 210 million people are currently living with COPD Tião is far from alone in his battle with COPD. Although still a relatively unknown disease compared to other lung conditions, such as asthma, and one that frequently goes undiagnosed, the
spiriva® is widely available in the HandiHaler®
latest World Health Organization (WHO) figures
and the respimat® Soft Mist™ Inhaler (SMI),
estimate that 210 million people are currently
a unique and technologically advanced new-
living with COPD and over three million people
generation inhaler.
died from the disease in 2005 – more than breast cancer and diabetes combined. Initially launched in 2002, spiriva® is now Breathlessness, the main symptom of COPD, is
available to COPD patients in more than 80
characteristically persistent and progressive, and
countries and is marketed jointly by Boehringer
has a serious impact on patients’ quality of life.
Ingelheim and Pfizer, Inc. It is the most prescribed
At its most severe, it even limits a patient from
medication for COPD and more than 10 million
simple tasks, such as washing and dressing. l
patients worldwide have so far benefited from taking spiriva®. Its efficacy and favourable safety profile have been demonstrated by an
Highlights Branded Prescription Medicines
extensive clinical development programme, which included approximately 20,000 patients. Long-acting bronchodilators, such as spiriva®,
spiriva®
are recommended by international guidelines as first-line maintenance therapy for COPD.
spiriva® (tiotropium) is an inhaled, long-acting anticholinergic. It is the only once-daily COPD medication that maintains 24-hour bronchodilation, resulting in significant and sustained long-term improvements in lung function and quality of life.
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Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
spiriva® positively impacts the clinical course of the disease, helping patients to live a more active life. COPD is often misdiagnosed as asthma, but an accurate diagnosis to distinguish between them is essential to ensure patients receive the best therapy. Early diagnosis and treatment of COPD can positively impact the clinical course of COPD and change the way patients live with their disease. Please refer to the chapter Research & Development for more information on the uplift® landmark trial reporting results in 2008 for tiotropium. l
human pharmaceuticals
mirapex®/sifrol®/mirapexin®/pexola®
treatment of idiopathic restless legs syndrome in 2006 based on its favourable efficacy and safety
Physicians already have over a decade of real-life experience in successfully using pramipexole for the treatment of patients with Parkinson’s disease (PD), and its effect in improving the motor symptoms of PD is well documented. The outstanding efficacy and good tolerability of pramipexole in PD has led to the drug, developed by Boehringer Ingelheim, being the most prescribed dopamine agonist brand worldwide. In addition to PD, mirapex®/sifrol®/mirapexin®/ pexola® (pramipexole) was approved for the
Battle against Parkinson’s Disease
profile. In 2008, pramipexole passed the benchmark of 1 billion USD in worldwide annual net sales. A once-daily formulation of pramipexole has been developed. The approval is expected in 2009, thus increasing the broad range of formulations from which physicians and patients can choose to meet patients’ individual needs. l pradaxa®
pradaxa® (dabigatran etexilate) is a once-daily oral anticoagulant for use in post-operative prevention of venous thromboembolism (VTE) after orthopaedic surgery. It will enable clinicians and patients to make decisions on choice of treatment appropriate to their clinical needs. 2008 was a very important and successful year for pradaxa®. The European Commission granted marketing authorisation for pradaxa® within all 27 EU member states for its first indication,
“I had been a professional artist since I finished art school in 1972 and my work was successful, so it was devastating being diagnosed with a neurological illness that could in all probability make me an invalid in the near future. Ten years have meanwhile passed since my diagnosis. I have great determination and have decided to fight against Parkinson’s disease and its effect on my life and that of my family.” Kristina
Löfdahl, Parkinson’s patient from Gothenburg, Sweden.
65
Highlights Branded Prescription Medicines
prevention of venous thrombo-embolic events in patients who have undergone total hip or knee replacement surgery. The approval of pradaxa® provides clinicians and patients a major advance in anticoagulation therapy for thrombo-embolic diseases. Initial market launch occurred in both the UK and Germany, with the first patient treated with pradaxa® in April 2008. Further marketing authorisations have been granted to Boehringer Ingelheim since then in key markets, including Canada, Brazil, New Zealand and Argentina.
Soon after this approval, the clinical and cost-
micardis®
effectiveness of pradaxa® was favourably appraised by several health technology assessment bodies. Leading the way was one of the most widely recognised, the UK’s National Institute for Health and Clinical Excellence (NICE), providing a significant endorsement for this new product. pradaxa® is a novel oral once-daily direct thrombin inhibitor from Boehringer Ingelheim research and development. It prevents thrombus (clot) formation by specifically and selectively inhibiting free and clot-bound thrombin, the central and essential enzyme in the coagulation cascade. pradaxa® has a favourable efficacy and safety profile, both in and out of hospital, for patients undergoing total hip or total knee replacement surgery.
Boehringer Ingelheim offers innovative options for the treatment of essential hypertension with micardis® (telmisartan 20/40/80 mg), our angiotensin II receptor blocker (ARB), and micardisplus®/micardis® hct (telmisartan in fixed dose combination with the diuretic hydrochlorothiazide 40/12.5; 80/12.5; 80/25 mg).
Please refer to the chapter Research & Devel opment for more information on the clinical
Hypertension is one of the most important but
trials reporting results in 2008 for dabigatran
modifiable risk factors for cardiovascular
etexilate. l
morbidity and mortality. The organ systems most affected from end organ damage are the heart, the main blood vessels, the brain and the kidneys.
Eve Knight,
Therefore, the primary goal of any antihyperten-
Chief Executive AntiCoagulation Europe
sive treatment is to prevent cardiovascular events, such as heart attacks or stroke, and finally reduce cardiovascular mortality. micardis® is characterised by high tissue concentrations, the longest duration of action in the ARB class and a tight binding to the angiotensin I receptor, which in clinical practice leads to blood pressure reductions over the full 24-hour period with a once-daily dosage.
“It is appalling that patients are still developing and dying from venous thrombo-embolism, which could very often be prevented by risk assessing every patient on admission to hospital and giving preventative treatment where needed. pradaxa®, a once-daily oral therapy for use in post-orthopaedic surgery, will enable clinicians and patients to make decisions on choice of treatment appropriate to their clinical needs.”
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Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Please refer to the chapter Research & Development for more information on the clinical trials reporting results in 2008 for telmisartan. l
human pharmaceuticals
Highlights Generic Prescription Medicines The Generic Prescription Medicines (GPM) business of Boehringer Ingelheim, which operates exclusively in the USA, consists of Bedford Laboratories, a division of Ben Venue Labora tories and Roxane Laboratories, Inc.
Injectable Generics – Bedford Laboratories
As one of the top generic injectable pharmaceutical companies in the USA, Bedford Laboratories offers a broad range of multisource injectables across multiple therapeutic classes, including oncology, cardiovascular, antiinfective and anaesthesia.
Oral Generics – Roxane Laboratories
In recent years, Roxane has further developed its differentiated strategy and contributed to the launch of many successful products. Allergic and non-allergic rhinitis Roxane Laboratories launched fluticasone in February 2006 for the treatment of allergic and non-allergic rhinitis. Since launch fluticasone has played an important role in achieving multisource business targets. Metabolic diseases – type 2 diabetes Roxane’s acarbose, an adjunct to diet to lower blood glucose in patients with type 2 diabetes, launched in May 2008, was an immediate success, achieving an overnight market share of 70 %. Hyperphosphataemia – kidney failure Roxane launched calcium acetate capsules in October 2008 for the control of hyperphospha-
Cardiovascular diseases
taemia in renal failure. Since launch, this has
Among Bedford’s portfolio is an abundant selec-
become an important addition to Roxane’s port-
tion of cardiovascular products, including anti
folio, with a market share of over 80 %. l
arrhythmics, e. g. diltiazem, treatment of atrial fibrillation and flutter, cardiomyopathy and blood pressure control (norepinephrine). Oncology Bedford Laboratories is committed to helping cancer patients with safe, effective and afford able medication. With 26 oncology products, amongst them being adriamycin and amifostine Bedford’s portfolio offers one of the largest lines of injectable oncology products in the US pharmaceutical market. Its portfolio addresses numerous cancer indications, such as ovarian, leukaemia and breast. In a very competitive oncology market, many of Bedford’s products rank No. 1 in unit market share. l
67
Highlights Generic Prescription Medicines
Ben Venue’s newly opened laboratory office building is a Leadership in Environmental and Energy Design (LEED) certified green building.
Highlights Consumer Health Care (CHC)
has a positive spillover to the new brand extension. With these latest additions to our CHC portfolio,
The buscopan® product family
the company has taken an important step to develop buscopan® into a global OTC franchise
buscopan® – the world’s leading over-the-counter (OTC) antispasmodic brand – is marketed in over 100 countries. Expanding the brand into a family of different sub-brands within abdominal categories was one of the most important strategic objectives in 2008. The buscopan® family in some important countries not only consists of antispasmodic products but, for example, of remedies against menstrual pain (buscofem®). In this respect, Boehringer Ingelheim Brazil successfully launched buscofem® – the first liquid-
and to position Boehringer Ingelheim as the leading abdominal specialist. l
dulcolax® – Intestinal irregularity and disruption
dulcolax®, our leading laxative brand, has been providing relief to sufferers of constipation in many countries for over 50 years. Through its active ingredient bisacodyl it has grown to become one of our flagship Consumer Health Care brands, trusted by millions worldwide.
filled softgel capsule with 400 mg ibuprofen on the Brazilian market – in August 2008. Part of its
In 2007, we redefined our global target market
success is the extraordinarily high consumer
for dulcolax® from “constipation” to “intes
awareness and positive image that the brand
tinal irregularity and disruption”, moving purely
buscopan® has acquired over more than 50
from looking at treatments to the future aim of
years in the Brazilian market. In July 2008, the
providing solutions for treatment, maintenance
launch of the first anti-heartburn product under
and prevention.
the buscopan® umbrella brand marked another major milestone in our global strategy. Interna-
In the USA, dulcolax® has a growing market
tional consumer research shows that a heartburn
share, and the brand continues to outperform
remedy ideally complements the buscopan®
the market. As a result it has now been rolled out
brand.
to France and Germany as well as being adapted for the South Korean and Spanish markets.
Argentina is the first country with buscasan® 24 (omeprazole 20 mg) on the market. This offers
The growth of the new product developments
targeted relief from heartburn for a full
dulcolax® m balance and dulcofibre®,
24 hours with just one capsule per day. Here
launched in Germany and Italy respectively in
again, the positive brand image of buscopan®
mid-2007, have continued to ensure that the
68
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
human pharmaceuticals
mucosolvan® – Building consumer excellence on medical heritage
The roll-out of the new global packaging design began in Germany with the biggest overhaul of the brand in over 50 years. The combination of globally aligned activities and strong local initiatives helped achieve record net sales and maintain the position of dulcolax® as the global market leader in an increasingly competitive environment.
franchise outperforms the market in both countries. In Germany, dulcolax® continued to strengthen it’s market leadership position, while the total market showed a slight decline. In Italy, the brand franchise has shown strong market value growth in a declining market. The further roll-out of dulcofibre® began in the fourth quarter, 2008. l
The active ingredient of mucosolvan® – ambroxol hydrochloride – was ori ginated and developed by Boehringer Ingelheim and first registered in Germany in August 1978. Since then, mucosolvan® formulations have been registered in more than 100 countries worldwide. mucosolvan® is our leading cough brand and maintained its No. 1 position in the global cough category in 2008. It is one of our international CHC brands, trusted by millions of users worldwide who seek to be freed of the annoyance of cough. lasolvan® (local brand name of mucosolvan® in Russia) growth is the best proof that comprehensive consumer information can be very successful.
mucosolvan® – Russia After the switch from prescription medicines in 2002, Boehringer Ingelheim Russia implemented a strong and successful consumerorientated marketing strategy and tactics, supported by the medical heritage of lasolvan®. lasolvan® showed a growth rate that significantly exceeded that of the market. lasolvan® growth in 2008 was 33 % (according to the RMBC database) and thereby Russia developed into our largest market for mucosolvan®. l After six years of rapid growth, Russia became the biggest mucosolvan® country market worldwide.
69
Highlights Consumer Health Care
serhat gürsoy “I produce medications and help to improve the well-being of people.”
70
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
product supply and industrial customer
actilyse® – A 20-year strike against stroke
For a long time, researchers had been looking for a therapy that would lead to the dissolving of fibrin clots – the major cause for acute myocardial infarction (AMI) and ischaemic stroke. AMI is still the main cause of death in the industrial nations, with around three million people suffering from it every year. During the last decade, the treatment of patients with AMI has been revolutionised. And the most marked change was the significant increase in the use of thrombolytic treatments. With the approval of the tissue plasminogen activator (tPA) actilyse® (alteplase), a joint product development between Genentech Inc. and Boehringer Ingelheim, the first thrombolytic treatment against heart attack was born in autumn 1987. The success story continued when actilyse® subsequently received approval for additional indications in the management of acute massive pulmonary embolism and for the treatment of acute ischaemic stroke, where it is still the only thrombolytic product in the USA.
In order to manufacture commercial amounts
started in August 1983 with the licensing of tPA
of tPA, Boehringer Ingelheim invested EUR 90
(alteplase) from Genentech Inc. covering the
million in the first biotechnology plant in
worldwide marketing rights, except for the USA,
Biberach, Germany, at the time the company’s
Canada and Japan. Even though both parties
largest single investment.
were as different as day and night – on the one hand a big pharmaceutical company and on the
In 1986, the development of actilyse® as the
other hand a young biotechnology company –
first biopharmaceutical drug in Germany paved
they complemented each other perfectly. In joint
Boehringer Ingelheim’s way to its current leader-
project teams both companies developed tPA and
ship position in biopharmaceutical manufactur-
succeeded in under five years of development
ing. The success story of actilyse® really got
with the approval in 1987 of actilyse® against
71
actilyse® – A 20-year strike against stroke
Columbus • • Bedford St. Joseph • • Petersburg
Bracknell • • Dortmund Ingelheim •• • Vienna •• Lugano • • Biberach Fornovo Blanquefort • • Reggello Malgrat•• Sant Cugat • Koropi
Guadalajara • • Mexico City
Bogota •
Itapecerica •
acute myocardial infarction in Germany.
commercial production plant for mammalian
Approval for the treatment of ischaemic stroke in
cell culture in Europe, which was inaugurated in
1996 in the USA and in Germany in 2002 was a
November 1986. This courageous investment in
breakthrough in the treatment concept of this
a future technology demonstrates once more
life-threatening disease caused by a blood clot.
Boehringer Ingelheim’s pioneering engagement
actilyse® immediately dissolves the blood clots
in the area of biopharmaceuticals, as actilyse®
that cause many strokes, drastically reducing the
is the first drug worldwide that was produced
amount of tissue damage in the brain. The time
from cell cultures in a large-scale approach.
window for getting the best results from actilyse® is up to three hours from the first signs of stroke.
Industrial Customer
The ecass 3™ trial has recently shown that stroke
Our business segment Industrial Customer has
can also be effectively treated in a time frame
the strategic role of supplying other biotechno
from 3—4.5 hours.
logy and pharmaceutical companies worldwide with the same developmental services and
To guarantee the worldwide supply of actilyse®,
production capabilities that support our own
Boehringer Ingelheim constructed the first
pharmaceuticals. The aim is to offer added value
72
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
product supply and industrial customer
C Bedford, USA Petersburg, USA
P
B
l l
St. Joseph, USA
●
Columbus, USA
l
Mexico City, Mexico
l
Guadalajara, Mexico
●
Bogotá, Colombia
l
Itapecerica, Brazil
l
Bracknell, UK
l
Blanquefort, France
Yamagata •• Fukushima Narita•
l
Sant Cugat, Spain
Shanghai •
Bogor •
l
Malgrat de Mar, Spain
l
Fornovo, Italy
l
Reggello, Italy
l
Lugano, Switzerland
l
Ingelheim, Germany
AH
l
l
Dortmund, Germany
l
Biberach, Germany
l
Vienna, Austria
l l
Koropi, Greece
l
Yamagata, Japan
l
Fukushima, Japan
l
Narita, Japan
l
Shanghai, China
l
B = Biopharmaceuticals
Bogor, Indonesia
l
AH = Animal Health
C = Pharma Chemicals P = Pharmaceuticals
Production
Status as of 31 December 2008
to customers ranging from research-led start-ups
Our three highly focused units provide compre-
to the major pharmaceutical groups. Industrial
hensive, world-class expertise, innovation and
Customer accomplishes this global mission
service for industrial customers as a full service
through three specialised units:
supplier.
• Biopharmaceuticals • Pharmaceuticals Production • Pharma Chemicals Together, they form a pharmaceutical network whose combined expertise, experience and service quality is unparalleled in the industry. Total Industrial Customer revenues of around USD 1 billion make it one of the largest industrial contract manufacturers in the pharmaceutical industry.
73
actilyse® – A 20-year strike against stroke
In addition, we conduct development and manufacturing of animal health vaccines in two centres in North America. l
Biopharmaceuticals – From mind to market
tered product). With current net sales of EUR 569 million, our Biopharmaceuticals business produces, besides for its industrial customer business also for its own captive use business (CUB). We currently market the four biopharma- ceuticals actilyse®, metalyse®, imukin® and beromun®. Biberach At our biotechnical plant in Biberach we focus on mammalian cell culture technologies for high-volume protein therapeutics, primarily
We offer the complete value chain from process
monoclonal antibodies (mAbs). In cell culture
development to biopharmaceuticals production
fermentation we have over more than 20 years
with a one-stop-shop service.
built up economic platform technologies, which are highly attractive for customers. Among these technology platforms we offer the proprietary bi-hex® high-expression system for cell line development and the upstream process. This platform allows the development of a stable, high
Biopharmaceuticals
Boehringer Ingelheim is one of the leading companies for the development and manufacture of biopharmaceuticals. We undertake this with an innovative spirit at our biopharmaceutical facilities in Biberach, Germany, and in Vienna, Austria.
expressing cell line, which is adequate for largescale manufacturing especially for mAbs. At the Biberach site, we offer sophisticated preformulation, formulation and pharmaceutical process development. The dosage form portfolio ranges from solutions, highly concentrated liquid formulations, suspensions, lyophilised or spraydried powders to inhalable presentations combined with state-of-the art proprietary application systems. To improve the one-stop-shop service for customers, we also develop liquid formulations for stable biopharmaceuticals in pre-filled syringes in our worldwide approved facilities. We have also invested in a new aseptic filling area with state-of-the-art isolator technology for double-chamber carpoules. The site has a very good track record in regula-
As one of the pioneers in biotechnology,
tory compliance and pre-approval inspections
Boehringer Ingelheim has operated for more than
as well as during multiple-company audits by
two decades in the development and manufac-
customers as well as authorities.
turing of biologics. This has earned us a reputation as one of the most experienced contract
Vienna
manufacturing organisations (CMOs), having
Boehringer Ingelheim Regional Center Vienna
brought 14 new biologic entities (NBEs) from
produces therapeutically active proteins from
“mind to market” (i. e. initial discovery to regis-
micro-organisms and yeast with state-of-the-art
74
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
product supply and industrial customer
fermentation technologies. Areas of manufactur-
ther platform technology for the manufacturing
ing expertise include protein therapeutics, protein
of high-quality plasmid DNA (pDNA). To date,
subunit vaccines, protein scaffolds, antibody
the process has been constantly optimised and
fragments and plasmid DNA for gene therapy.
fermentation titers of > 3 g/l have been achieved.
Interferon beta-1b, one of the top twenty bio-
In 2008, the Vienna site and Geneart started a
pharmaceutical blockbusters, is manufactured at
cooperation comprising a value chain from DNA
this plant. A broad host range for fermentation
design up to large-scale GMP manufacturing of
from E. coli, Saccharomyces cerevisiae, Hansenula
pDNA therapeutics for gene therapy and vaccin
polymorpha and Pichia pastoris is available at the
ation.
site all with high-titer processes. The genome integration system in E. coli is suitable for large,
For downstream processing, efficient harvest,
complex molecules, since the gene of interest is
high-yield, matrix-assisted refolding and purifi-
stably integrated into the genome.
cation technologies, such as crystallisation, chro-
For the production of difficult to express peptides
high-performance liquid crystallography, are in
matography, ultra/diafiltration, and large-scale and small proteins, the proprietary Npro auto-
place. A systematically multi-stage approach for
protease technology platform can be the appro-
the development of crystallisation processes in
priate system of choice. The autoprotease of the
cell lysates, intermediates or purified bulks was
fusion protein can be used as a tag for affinity
set up and a large-scale process with 20 kg pro-
chromatography and approvable to a whole
tein per batch for crystallisation was implement-
range of protein therapeutics. It facilitates refold-
ed. Due to our very good regulatory compliance
ing and provides the correct N-terminus.
track record in launch and secured supply and
For the treatment of diseases via direct gene
folio of our Vienna site today consists of seven of
transfer, our Vienna operation developed a fur-
the top 20 pharmaceutical companies. l
our state-of-the-art technology, the client port-
Technologies (Biopharmaceuticals) Host
Technology
Vienna, Austria
• Microorganisms and yeast • High expression systems fermentation • High throughput screening in upstream and downstream development • Purification technologies: e. g. crystallisation, reversed phase HPLC • Refolding technologies • Pegylation
Biberach, Germany
• Mammalian cell culture
• • • • •
Biopharmaceuticals
Fill & Finish
Non-glycosylated proteins • In Biberach Antibody fragments Peptides Protein scaffolds Plasmid DNA
• High expression systems • Glycosylated therapeutic • High throughput proteins screening in upstream and • Monoclonal antibodies downstream development • Fusion proteins • Purification technologies • Formulation development for proteins and gene therapeutics
Status as of 31 December 2008
75
Products
• • • • • •
Aseptic filling Lyophilisation Liquid vials Lyo-vials Pre-filled syringes Double chamber carpoules
Pharmaceuticals Production
been achieved by using common lean production methods and by fostering a strong performance
Pharmaceuticals Production guarantees product availability for our internal and external customers. It manufactures drug product for our Human Pharmaceuticals business and for external partners for the global markets.
culture within the framework of a growing involvement of external production partners. In 2008, one-third of the packing units were produced by contract manufacturers. An important step in this context was the sale of our production facility in Reims, France, to a leading European contract manufacturer. This will provide future growth for the factory in Reims and guarantee long-term supply for Boehringer Ingelheim as a customer. Business process excellence has also resulted in competitive cost of goods, while reliably providing our sales organisation with high-quality
Fast to the market – The launch sites
products.
Innovative drugs are launched from our manufacturing sites in Germany and the USA. In 2008,
Contract manufacturing
our Ingelheim site in Germany guaranteed the
The key success factor of the contract manufac-
launch of pradaxa® for the indication preven-
turing services of Boehringer Ingelheim is its
tion of venous thrombo-embolism (VTE) after
world-class pharmaceutical production network
elective hip and knee replacement by supplying
enhanced by business process excellence.
drug product for the European market. In Ingelheim a new 10,000 m² packaging centre
The wide range of manufacturing technologies
started production. It was designed according to
established in our Pharmaceuticals Production
current material flow requirements. This
facilities is offered in the form of contract manu-
completed the high-tech manufacturing centre at
facturing services to external industrial clients,
the site.
as well as for captive use. Boehringer Ingelheim provides highly valuable contract manufacturing.
The sites are well-prepared for future capacity
These are enabled by the synergies between our
needs triggered by potential new drugs, in par-
captive production and the services for our ex-
ticular flibanserin from our US site in Columbus,
ternal clients.
Ohio, and pradaxa® and spiriva® respimat® from Germany.
Captive production has taught us for years how to guarantee a reliable commercial supply of safe
Global presence
products with our robust quality and our compli-
Our network of sites in 2008 comprised our
ance focus.
global export sites in Germany, the USA, Japan, China, Greece, Spain, Italy, Switzerland, Mexico,
Our presence on three continents, our broad set
Brazil, Colombia and Indonesia.
of manufacturing and packaging technologies and certification by the leading regulatory agen-
Increased efficiency combined with improved
cies allow us to find the optimal solution for our
flexibility in the manufacturing network has
clients. l
76
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
product supply and industrial customer
Technologies (Pharmaceuticals Production) Non-sterile Solids
Sterile Semi-solids
Liquids
Inhalatives
Bedford, USA Biberach, Germany
l
Bogor, Indonesia
l
Bogotá, Colombia
l
l
Bracknell, UK Columbus, USA
l
l
l
l
l
l
l l
Dortmund, Germany
l
Fukushima, Japan
l
Ingelheim, Germany
l
Itapecerica, Brazil
l
l
l
Koropi, Greece
l
l
l
Lugano, Switzerland
l
l
l
Mexico City, Mexico
l
Narita, Japan
l
Reggello, Italy
l
l
l
l
l
Sant Cugat, Spain
l l
Shanghai, China
l
Yamagata, Japan
l
Status as of 31 December 2008
77
Injectables
Contract manufacturing
Pharmaceuticals Production
l
activities in Ingelheim, Germany, under a single
Pharma Chemicals
roof. With our resomer® activities we keep at
At Pharma Chemicals we benefit from the experience and competence of the whole Boehringer Ingelheim group.
the cutting edge in enabling new drug delivery approaches and new surgical device design. Active pharmaceutical ingredients (API) manufacture and new chemical entities (NCE) development Our Chemicals Division produces Boehringer Ingelheim’s own APIs in a global production network, as well as offering manufacturing
Contract development and manufacturing
and development services to our industrial
We take a flexible approach to the individual
customers.
needs of pharmaceutical companies that opt to buy rather than make their proprietary new
Our five chemical production sites in Germany,
chemical entities (NCEs). Cooperation is under-
France, Italy, Spain and the USA are operated
taken in stages, as desired, and tailored precisely
as a worldwide network. Germany, as our launch
to the customer’s requirements. We also manu-
site, has state-of-the-art facilities for the
facture and market active pharmaceutical ingre-
development of NCEs, all the required expertise
dients (APIs) that are well-established world-
and resources for launching new products and
wide – our API Classics. These cover important
highly flexible, multi-purpose production plants.
indication areas for healthcare systems and play
Our facilities enable active ingredients to be
a major role in significant pharmaceutical mar-
synthesised chemically or extracted and refined
kets. We are also a world leader in extracting ac-
from medicinal plants. We have the capacity
tive ingredients from medicinal plants and have
range to seamlessly upscale the production of
seamless command of the whole process chain
extremely complex chemicals from one kilo to
from plant cultivation on our own plantations to
multi-ton levels. Our Ingelheim site successfully
making marketable pharmaceuticals.
supported the 2008 launch of pradaxa® with the development and supply of the active ingre-
Besides the supply of active ingredients, we
dient dabigatran etexilate. We complement our
also offer resorbable polymers for medical and
worldwide chemical production network with
pharmaceutical applications. resomer® is firmly
strong partners for the manufacturing of starting
established in this niche market. Recently, we
materials and intermediates for our APIs. In
completed a new production and laboratory
2008, we started a strategic production alliance
building which brings our biodegradable polymer
in China. l
Technologies (Pharma Chemicals) Synthesis API
Phyto chemicals
Process development
Regulatory registration support
Toxicology process safety
l
l
l
l
l
Blanquefort, France
l
Ingelheim, Germany
l
Fornovo, Italy
l
l
Malgrat de Mar, Spain
l
l
Petersburg, USA
l
l
Status as of 31 December 2008
78
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
l
l
product supply and industrial customer
Manufacturing excellence in our centre
given it the capacity to be our global supplier of
for global animal health vaccines
porcine, bovine and equine vaccines at a time of growing worldwide demand for preventative approaches.
In pursuit of our aim to become a world leader in vaccines for animals, we have concentrated the development and manufacturing of almost all of our vaccines at our multi-purpose US facility in St. Joseph, Missouri.
Our strong and ever-growing presence in the swine vaccine segment reflects a series of breakthroughs made at St. Joseph. ingelvac® Aujeszky vaccine was developed there as our first innovative pig vaccine in the late 1980s, followed by i ngelvac® prrs, ingelvac® m.hyo, enterisol® ileitis, and only recently, ingelvac circoflex®. Both commercial and animal welfare consider ations are driving this trend and our vaccine facility has had to keep up with the fast-expanding market. From an annual 150 million vaccine
The St. Joseph plant is equipped with cutting
doses in 2001, we now produce around 400
edge technologies such as bioreactors and fer-
million and are targeting almost 700 million
menters for cell and microbial fermentation and
doses by 2012. Our St. Joseph site currently
large freeze dryers. Furthermore, the facility
manufactures more than 100 vaccine types. l
holds both an EU good manufacturing practice (GMP) and a USDA licence representing the highest quality and compliance standard in the animal health industry, which allows vaccine registrations in almost all countries outside the USA. Locating global production in the USA has a particular advantage, as US regulations make it difficult to import vaccines into the country – our largest market for our Animal Health products. The constant updating and expansion of the highly flexible St. Joseph plant has made it one of the leading vaccine facilities in the world and has
Core competencies in vaccine production (Boehringer Ingelheim Vetmedica. Inc) Swine vaccines Guadalajara, Mexico
l
St. Joseph, USA
l
Equine vaccines
Bovine vaccines
l l
l
Status as of 31 December 2008
79
Pet vaccines
Manufacturing excellence in our centre for global animal health vaccines
Poultry vaccines
l l
helen lewis and mary “We saw an improvement after a week.”
80
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
animal health
My lion queen leaps again!
Mary is a 14-year-old cat who is “head of the household” at the home she shares with Helen Lewis next to the pub in the village of Benenden in southeast England. Helen, a sprightly 81-year-old, explains, “I can’t remember why we called her Mary, but she’s a very independent cat and has always known what suits her best. But she’s a very gentle soul and is remarkably friendly and dignified; even our vet has commented how well behaved she is. I think she has a sense of humour and a conscience, and I like talking to her, but of course, friends tease me over that!” says Helen.
It was a couple of years ago when Helen, a trained pharmacist, spotted that Mary was showing the first signs of arthritis. “I recognised that she was getting slower. She used to be a great leaper, springing from tables and high up places. She was also climbing the stairs step by step, whereas before she would bound up them. It was and I was checking her back legs one day and she hissed fiercely that it became clear that she was suffering from pain. Mary could tell there was something slightly different about her when I gave her the antiarthritis medication the vet prescribed. I would say without a shadow of a doubt it works and we saw an improvement in a week or so and Mary
Highlights Animal Health ingelvac circoflex® – successful roll-out to Europe and Asia
ingelvac circoflex® has been our most successful product in Animal Health in 2008. The roll-out of this innovative vaccine for fighting PCVD was extended to Europe and Asia.
began scampering around much more. We’re delighted – she is such a comfort and I’d do
ingelvac circoflex® is the first vaccine that
anything for her.” l
protects pigs against the early and late form of
81
My lion queen leaps again!
porcine circovirus disease (PCVD) with only one
ubrolexin® – Our new mastitis treatment
injection around weaning. Other vaccines have
meets strong demand
to be given twice. This reduces stress for the animals and helps farmers to save expensive labour costs. The combination of a purified circovirus antigen (PCA) and a non-mineral oil slow release adjuvant allows a unique synthesis of highest efficacy and extreme safety properties. These outstanding product characteristics have made ingelvac circoflex® the global market leader in its market segment, with more than 100 million doses sold in less than two years after the first national marketing authorisation. The global roll-out has just begun with Europe and Asia moving into full supply in 2009. The first convenient combinations of ingelvac circoflex® with another core swine vaccine of Boehringer Ingelheim Animal Health, ingelvac
As any dairy farmer can tell, mastitis is the main disease affecting cows today. In October 2008, Boehringer Ingelheim launched ubrolexin®, a novel broadspectrum intramammary treatment and a highly effective tool in the control of mastitis.
mycoflex®, have also just recently been licensed in North America. l
With constant zootechnical improvement to increase milk yields, a large proportion of dairy cattle suffer from mastitis, an infection of the mammary glands. Triggered by a variety of pathogens, mastitis severely impacts the cow’s health and milk quality, and reduces output. The need for quick reaction upon occurrence of mastitis is key to maintaining every chance for
ingelvac circoflex®
successful cure. The availability of a first-line treatment, which can be applied by farmers themselves, then becomes of paramount import ance. Matching this need, ubrolexin® provides farmers with exceptionally high efficacy and safety in addition to convenience of use: infected quarters only have to be treated twice with ubrolexin®, leaving an interval of 24 hours between treatments. ubrolexin® met exceptionally strong demand on its initial launches in the Netherlands and the United Kingdom in October and by early 2009 it will be available in all the main EU markets.
ingelvac circoflex® is the first one-dose vaccine for the reduction of the early and late form of PCVD.
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Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
The novelty of ubrolexin® is the intelligent way it combines two target spectrum antibiotics at a specific ratio of concentration into a broad spectrum product. By making use of the synergistic
animal health
effects achieved through the combination,
Following the important launch in the USA the
u brolexin® reaches an efficacy which by far
previous year, vetmedin® was launched in 2008
exceeds that of the individual components. This
and very well-received in the remaining major
reduces the total amount of antibiotic needed for
companion animal market Japan. vetmedin® is
an effective treatment and at the same time limits
today sold in more than 30 countries around the
the risk of resistance development. Against a
world and is now market leader in the global
background of widespread criticism of the use of
canine cardiology segment. l
antibiotics on food-producing animals, these effects, due to the synergistic activity in u brolexin®, are important contributions to
ingelvac® prrs mlv – a great success in China
the prudent use of antibiotics in mastitis treatment. l
vetmedin® reached a major milestone in 2008 with the publication of the longanticipated quest™ study.
During 2008, Boehringer Ingelheim Animal Health again provided an efficient innovative vaccine against outbreaks of a serious pig disease in Asia, especially in China.
Commissioned by Boehringer Ingelheim, the
Porcine reproductive and respiratory syndrome
study, the largest of its kind ever conducted,
(PRRS) is another major viral disease threatening
involved pet dogs with congestive heart failure
modern pig production worldwide. Since the
quest™ – Good news for dog owners
(CHF) caused by mitral valve disease.
mid-1990s, Boehringer Ingelheim Animal Health has been the leading supplier in this vaccine segment and 2008 provided additional growth, namely in the biggest swine producing economy, China. Starting in 2007, China suffered from a
The primary aim of the quest™ study (Quality of
new, highly virulent strain of PRRS which killed
Life and Extension of Survival Time) was to ana-
a large number of pigs and swept rapidly across
lyse the effect on survival of dogs suffering from
the country. Early on, Boehringer Ingelheim
congestive heart failure due to mitral valve
initiated a collaboration with the Shanghai Vet-
insufficiency, the most common form of heart
erinary Research Institute to establish scientific
disease in dogs. Under the guidance of Professor
proof for the cross-protection of ingelvac®
Jens Häggström, University of Uppsala, Sweden,
prrs mlv against these newly emerging Chinese
32 renowned cardiologists from 11 countries
strains. Results became available in mid-2008
in Europe, North America and Australia
and fostered a strong demand for our unique
participated in the study. The success of the
attenuated PRRS vaccine. Meanwhile, highly
quest™ study can be attributed to the close
virulent strains of PRRS have emerged in other
cooperation between scientists from Boehringer
Asian countries and strong global demand for
Ingelheim and the most important academic
ingelvac® prrs mlv is projected for the coming
research institutes. Results were presented to the
years. l
veterinary scientific community at two important congresses.
83
Highlights Animal Health
Samples of the product portfolio Branded Prescription Medicines Respiratory diseases Chronic obstructive pulmonary disease (COPD)
COPD is caused by noxious stimuli, such as cig
and asthma are among the most prevalent
arette smoke or air pollution. COPD can manifest
chronic diseases affecting the lung, and cause
itself as chronic bronchitis with cough and
significant morbidity and premature deaths
sputum, or as emphysema caused by destruction
worldwide.
of the lung tissue. The course of COPD is charac terised by occasional sudden worsening of symp
COPD
toms called acute exacerbations.
Chronic obstructive pulmonary disease is a dis ease of the lung in which the airways become
Asthma
narrowed. This leads to a limitation of airflow
Asthma is a chronic disease involving airway in
causing shortness of breath and other respiratory
flammation in response to exposure to asthma
symptoms. The airflow limitation is only partially
triggers, such as allergens. Airway inflammation
reversible and usually worsens gradually over
causes airways to narrow, mucus to increase and
time.
breathing to be more difficult. In the early stages of disease, this airflow limitation is fully reversi ble and patients can be free of symptoms between attacks.
84
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
product portfolio
Indications
Brand names
Active ingredients
• Chronic obstructive pulmonary disease (COPD)
spiriva®
tiotropium bromide
Maintenance treatment of patients with COPD (chronic obstructive pulmonary disease, including chronic bronchitis and emphysema), the maintenance treatment of associated dyspnoea and for prevention of exacerbations.
• Bronchospasms associated with reversible obstructive airway diseases
combivent®
ipratropium bromide, salbutamol
Treatment of bronchospasms associated with reversible obstructive airway diseases in patients requiring more than one bronchodilator.
• Chronic obstructive pulmonary disease (COPD) • Chronic bronchitis • Asthma
atrovent®
ipratropium bromide
Bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis, emphysema and asthma.
• Bronchial asthma • Chronic bronchitis
berodual® bronchodual® duovent®
fenoterol, ipratropium bromide
For prevention and treatment of symptoms in chronic obstructive airway disorders with reversible bronchospasm, such as bronchial asthma, and especially chronic bronchitis, with or without emphysema.
• Bronchial asthma
berotec® dosberotec®
fenoterol
Symptomatic treatment of acute asthma attacks, prophylaxis of exercise-induced asthma, symptomatic treatment of bronchial asthma and other conditions with reversible airway narrowing, e. g. chronic obstructive bronchitis.
• Bronchial asthma
inflammide®
budesonide
Chronic control of symptoms and signs of bronchial asthma.
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Samples of the product portfolio Branded Prescription Medicines
Respiratory diseases (continued)
Diseases of the central nervous system Mental and neurological diseases, such as
in the legs as well as disturbed sleep resulting in
depression and Parkinson’s disease, significantly
daytime tiredness or sleepiness. The sensations
impact patients and their families, and are a
are felt deep within the legs and are described as
significant burden to society.
creeping, crawling or aching.
Parkinson’s disease
Major depressive disorder
Parkinson’s disease (PD) is a degenerative dis
Major depressive disorder (MDD) is a mental dis
order of the central nervous system. Patients usu
order characterised by a low mood and loss of
ally notice motor symptoms, like hand tremor
interest or pleasure in usual activities. The diag
(shaking), as their first sign of the disease, which
nosis is based on the patient’s self-reported ex
progresses eventually to include shaking of the
periences. MDD is a highly prevalent disease that
arms, legs or head. Other motor symptoms that
completely disrupts patients’ lives and is a major
develop over time include stiffness that often
cause of absenteeism from work worldwide.
results in loss of facial expression and a gradual slowing or loss of motion or “freezing”. About
Generalised anxiety disorder
30–40% of patients also suffer from non-motor
Generalised anxiety disorder (GAD) is character
symptoms associated with PD, such as depres
ised by excessive, uncontrollable and often
sion and sleep disorders. The primary symptoms
irrational worry about everyday things. This
are the results of decreased stimulation of brain
excessive worry often interferes with the patient’s
cells by lack of the neurotransmitter dopamine.
life. Patients often have physical symptoms such as fatigue, headaches, nausea, pain, sweating or
Restless legs syndrome (RLS) Restless legs syndrome (RLS) is a common neu rological disorder characterised by an uncontrol lable urge to move the legs, usually accompanied by unpleasant and sometimes painful sensations
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sleeping difficulties.
product portfolio
Indications
Brand names
Active ingredients
• Bronchial asthma • Allergic rhinitis • Allergic skin disorders with pruritus
alesion® flurinol®
epinastine
Indications
Brand names
Active ingredients
• Parkinson’s disease (PD) • Restless legs syndrome (RLS)
sifrol® mirapex® mirapexin® pexola®
pramipexole
Symptomatic treatment of idiopathic Parkinson’s disease. It may be used as monotherapy or in combination with levodopa. Symptomatic treatment of idiopathic restless legs syndrome.
• Depression • Diabetic neuropathic pain (DNP) • General anxiety disorder (GAD)
cymbalta® xeristar®
duloxetine hydrochloride
Treatment of depression. Treatment of diabetic neuropathic pain (DNP). Treatment of general anxiety disorder (GAD).
• Diabetic neuropathic pain (DNP)
ariclaim®
duloxetine hydrochloride
Treatment of diabetic neuropathic pain (DNP).
• Sleep disorders
lendormin® lendorm® lindormin® sintonal®
brotizolam
Short-term treatment of disorders of initiating and maintaining sleep.
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Samples of the product portfolio Branded Prescription Medicines
Prophylactic treatment of bronchial asthma. Prophylaxis and symptomatic treatment of allergic rhinitis, allergic skin disorders with pruritus, such as urticaria, and eczema/dermatitis.
Cardiovascular diseases Cardiovascular diseases are the leading causes of
Acute myocardial infarction
death in many countries, and are still increasing
An acute myocardial infarction, or heart attack,
in prevalence.
is an acute event that occurs when a thrombus or clot suddenly prevents blood flow to an area of
Stroke
the heart muscle. Unless the blood flow is restored
Stroke is the rapidly developing loss of brain
quickly, the affected section of heart muscle
functions due to a blockage of the blood flow
becomes permanently damaged. Heart attack is
to the affected brain tissue. This can be due to
a leading cause of death in all developed coun
ischaemia (lack of blood supply) caused by
tries.
thrombosis or embolism, or due to a bleeding. As a result, the affected area of the brain is unable
Hypertension
to function and the damage quickly becomes
Hypertension, also referred to as high blood pres
permanent, if untreated. Stroke is an acute event
sure, is a chronic disease in which the blood
needing emergency diagnosis and intervention.
pressure is chronically elevated. Hypertension is
Stroke is one of the leading causes of death and
one of the major risk factors for strokes, heart
long-term disability in the developed world.
attacks, heart failure and chronic renal failure.
Symptoms of a transient ischaemic attack (TIA) are similar to stroke, but lasting for only a few minutes or hours. As a TIA may precede a stroke, emergency medical care and subsequent preven tive treatment is necessary.
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product portfolio
Indications
Brand names
Active ingredients
• Hypertension
micardis® micardisplus® micardis® plus micardis® hct co-micardis®
telmisartan; telmisartan, hydrochlorothiazide
Treatment of essential hypertension.
• Secondary prevention of aggrenox® stroke or transient ischaemic asasantin® attacks (TIA) asasantin® retard persantin® plus
dipyridamole, acetylsalicylic acid
Prevention of stroke following a first stroke or transient ischaemic attacks. persantin® plus as above and adjunct to coumarin anticoagulants in the prevention of post-operative thromboembolic complications of cardiac valve replacement.
• Hypertension
clonidine
All forms of high blood pressure, unless caused by phaeochromocytoma.
• Acute myocardial infarction, actilyse® acute massive pulmonary embolism • Acute ischaemic stroke • Catheter clearance due to thrombotic occlusion
alteplase
Fibrinolytic treatment of acute myocardial infarction, acute massive pulmonary embolism, acute ischaemic stroke and for catheter clearance due to thrombotic occlusion.
• Acute myocardial infarction
metalyse®
tenecteplase
Fibrinolytic treatment of acute myocardial infarction.
• Ventricular tachycardia
mexitil® mexitilen®
mexiletine
Serious symptomatic ventricular tachy cardic heart rhythm disturbances.
• Hypertension
motens® caldine® tens® midotens®
lacidipine
Treatment of essential hypertension.
catapresan® catapres® catapressan® atensina®
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Samples of the product portfolio Branded Prescription Medicines
Cardiovascular diseases (continued) Venous thrombo-embolism Patients undergoing orthopaedic surgery are at
venous insufficiency in the lower extremity often
considerable risk of developing deep vein throm
develops, resulting in chronic pain, venous
bosis in the legs or a potentially fatal pulmonary
ulceration, swelling, and skin changes in the
embolism. Both are also known as venous
affected leg. To prevent any event and its conse
thrombo-embolism (VTE). In the longer term,
quences, the majority of patients receive some
thrombo-embolic events may recur and chronic
kind of thromboprophylaxis.
Viral diseases Acquired immune deficiency syndrome Acquired immune deficiency syndrome (AIDS) is a set of symptoms and infections resulting from the damage to the human immune system caused by the human immunodeficiency virus (HIV). If untreated, this condition progressively reduces the effectiveness of the immune system and leaves individuals susceptible to opportunistic infections and tumours. Babies of infected mothers are at risk of getting the virus during pregnancy, childbirth or breastfeeding.
Urological diseases Benign prostate hyperplasia Benign prostate hyperplasia (BPH) refers to an enlargement of the prostate in middle-aged and elderly men, which can lead to problems with urination and consequent infections of the urinary tract.
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product portfolio
Indications
Brand names
Active ingredients
• Primary prevention of venous thrombo-embolic events after orthopedic surgery
pradaxa® pradax™ pradaxar™
dabigatran etexilate
Indications
Brand names
Active ingredients
• HIV/AIDS
viramune®
nevirapine
Available as tablets and suspension for adults and children – for the combination therapy of HIV-1 infection and for the prevention of mother-to-child transmis sion of HIV-1 in pregnant women who are not taking antiretroviral therapy at time of labour.
• HIV/AIDS
aptivus®
tipranavir
Capsule and oral solution – co-adminis tered with 200 mg of ritonavir, is indicated for combination antiretroviral treatment of HIV-1-infected patients with evidence of viral replication, who are treatmentexperienced and infected with HIV-1 strains resistant to more than one protease inhibitor.
Indications
Brand names
Active ingredients
• Benign prostate hyperplasia (BPH)
flomax® alna® josir® pradif® secotex® urolosin® mecir®
tamsulosin
Lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH).
• Benign prostate hyperplasia (BPH)
flomax® cr alna® ocas® pradif® t urolosin® ocas®
tamsulosin, orally controlled absorption system
Lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH).
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Samples of the product portfolio Branded Prescription Medicines
Primary prevention of venous thromboembolic events (VTE) in adults after elective total hip or knee replacement surgery.
Samples of the product portfolio Consumer Health Care Cough and cold mucosolvan® (ambroxol) and bisolvon® (brom
clearance mechanisms of the respiratory tract,
hexine) are both indicated for secretolytic therapy
which play an important role in the body’s nat-
in bronchopulmonary diseases associated with
ural defence mechanisms. Ambroxol stimulates
abnormal mucus secretion and impaired mucus
synthesis and release of surfactant by type II
transport.
pneumocytes.
Cough is the most common symptom of clinical
bisolvon® (bromhexine), available for all age
importance and the most frequent reason to
groups, has been on the market since 1963.
consult a doctor. The clinical symptoms of cough
Bromhexine is contained in various formulations
and expectoration have led to the development
of bisolvon®. There are high and low strength
of drugs that affect respiratory mucus, i.e. the
syrups 8 mg/5 ml, 4 mg/ml, tablets and soluble
mucoactive agents.
tablets (both with 8 mg bromhexine) and solu tion for oral use 10 mg/5 ml), adapted to the need
mucosolvan® (ambroxol), which promotes
of the patients. Bromhexine is a synthetic deriva
mucus clearance, facilitates expectoration and
tive of the herbal active ingredient vasicine. It has
eases productive cough, allowing patients to
been shown to increase the proportion of serous
breathe freely and deeply, is the world’s leading
bronchial secretion, making it more easily
cough brand. It is available in many different for
expectorated. Bromhexine also enhances mucus
mulations.
transport by reducing mucus viscosity and by activating the ciliated epithelium.
Ambroxol is a mucoactive drug with several properties, including secretolytic and secreto motoric actions that restore the physiological
Sore throat mucoangin® (ambroxol) is the best documented
uous pain in the throat maximised when swal
product and is well tolerated in its category of
lowing. The main goal of the treatment is thus to
pain relief in acute sore throat.
reduce pain.
Pain in sore throat is the hallmark of acute
The main property of ambroxol is the local an
pharyngitis, usually caused by a viral infection.
aesthetic effect, described first in the late 1970s,
The infection is self-limited and the patient
but explained and confirmed in more recent
recovers normally in a couple of days. What is
work.
most bother some for the patient is the contin-
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product portfolio
Indications
Brand names
Active ingredients
• Acute and chronic bronchopulmonary diseases
mucosolvan® motosol® mucosan® surbronc® vaksan® lasolvan® mucosal® mucopect®
ambroxol
Secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport.
• Acute and chronic bronchopulmonary diseases
bisolvon®
bromhexine
Secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport.
• Cough
silomat® dmp
dextrometorphane
Symptomatic treatment of irritable, non-productive cough.
Indications
Brand names
Active ingredients
• Sore throat
mucoangin® lysopadol®
ambroxol (lozenges)
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Samples of the product portfolio Consumer Health Care
Pain relief in acute sore throat.
Gastrointestinal diseases In our gastrointestinal portfolio, we offer
Other products within the dulcolax® m
several brands, such as dulcolax®, dulcolax®
b alance franchise include dulcoease® (stool
m balance, dulcofibre®, laxoberal® and
softener), dulcoenema® and dulcofibre®.
buscopan®, as well as the heartburn brand z antac®.
Abdominal cramping, pain and discomfort are common ailments. Approximately one in four
Within the dulcolax® franchise, Boehringer
persons worldwide suffers on a regular basis.
Ingelheim markets a range of products for the treatment, regulation and prevention of intes
buscopan® is an antispasmodic product with
tinal irregularity and disruption. The primary
the active ingredient hyoscine butylbromide.
ailment within this area is constipation, for
The product is basically a natural substance
which dulcolax® tablets are today the main
extracted from Duboisia plant species as scopol-
source of treatment.
amine (hyoscine) and chemically modified to the quaternary ammonium compound hyoscine
dulcolax® tablets have a special enteric com
butylbromide. As an antispasmodic product,
fort coating to ensure that the active ingredient is
buscopan® acts directly on the site of abdominal
transported to work only where it is needed – in
pain by relaxing the muscles of the gastrointesti
the large intestines. Here it stimulates the natural
nal tract.
movement of the bowels to provide gentle, predictable relief within 6–12 hours. One to two
This means buscopan® relieves abdominal pain
tablets taken before going to bed will still provide
by directly treating its main cause – abdominal
relief the next morning.
cramp or spasm.
The active ingredients bisacodyl (dulcolax®
Several buscopan® line extensions are available
tablets and suppositories), sodium picosulfate
today – the mono-variant and in different com
(dulcolax® pearls, liquid drops and syrup) and
binations with analgesics (paracetamol, ibu
macrogol (dulcolax® m balance) are scien
profen and metamizol/dipyrone) – and different
tifically proven to provide gentle and effective
formulations (tablets, drops, suppositories, syrup
relief.
and solutions for intravenous injection).
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product portfolio
Indications
Brand names
Active ingredients
• Constipation
dulcolax®
bisacodyl (tablets, suppositories), sodium picosulfate (drops, pearls)
Laxative for use in patients suffering from constipation. In preparation for diagnostic procedures, in pre- and post-operative treatment and in conditions, which require defecation to be facilitated.
• Constipation
dulcolax® m balance
macrogol 4000
Symptomatic treatment of constipation for adults and children from eight years onwards.
• Constipation
dulcofibre®
glucomannan
Reactivation/regulation of bowel move ment; helps to maintain regularity.
• Constipation
laxoberal® laxoberon® guttalax®
sodium picosulfate (drops, pearls, tablets)
Laxative for use in cases of constipation and in conditions which require defecation to be facilitated.
• Abdominal cramping
buscopan® buscapina®
hyoscine butylbromide
Treatment for the relief of abdominal cramping, pain and discomfort.
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Gastrointestinal (continued)
Vitamins and supplements pharmaton® is a multivitamin and mineral
pharmaton® kiddi®, a range of products
supplements brand developed to enhance peo
designed for children, contains selected vitamins,
ple’s physical and mental well-being. A full range
minerals and key nutrients that are very import
of products adapted to the needs of different
ant for growth. It is especially recommended in
target audiences has been developed that work
the preventive treatment of vitamin deficiencies.
in harmony with the body. pharmaton® matruelle is a pre-natal multi pharmaton® core, a range of products for
vitamin for active planning, pregnant and lactat
adults, contains a synergic and unique blend
ing women, containing all important micronu
of vitamins, minerals and trace elements and
trients for mother and baby, such as vitamins,
standardised Ginseng G115 extract. The main
minerals and omega-3 fatty acids, to cover the
target indications are: exhaustion, tiredness,
increased needs for these substances in those
decreasing concentration and mental alertness.
particular periods. Moreover, it helps to protect
Numerous clinical studies have shown that a
against embryonal neural tube diseases of the
regular intake of pharmaton® has a positive
foetus and against iron and folic acids anaemia
effect on mental and physical performance and
during pregnancy.
well-being.
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product portfolio
Indications
Brand names
Active ingredients
• Heartburn
zantac® (*)
ranitidine
Relieves heartburn associated with acid indigestion and sour stomach. Prevents heartburn associated with acid indigestion and sour stomach brought on by certain foods and beverages.
* only available in the USA
Indications
Brand names
Active ingredients
• Tiredness • Decreasing concentration
pharmaton®
standardised ginseng extract, vitamins, minerals, trace elements
For states of exhaustion (e. g. caused by stress), tiredness, feeling of weakness, decreasing concentration as well as decreasing mental alertness.
• Children’s multivitamin
pharmaton® kiddi®
vitamins, minerals, amino acids
Increasing demand for vitamins, minerals and amino acids, especially during the period of growth. Preventive treatment in case of vitamin deficiencies, e. g. restricted diets, convalescence, loss of appetite, following illness, infection or surgery.
• Prophylaxis of iron and folic acid deficiency during pregnancy
pharmaton® atruelle m
vitamins, minerals, trace elements, omega-3 fatty acids [docosahexaenoic acid (DHA)]
For women of child-bearing age intending to become pregnant, already pregnant and lactating, to cover the increased needs for vitamins, minerals, trace elements and DHA. To provide protection against embryonal neural tube diseases of the foetus, and prophylaxis of iron and folic acid anaemia during pregnancy.
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Samples of the product portfolio Consumer Health Care
Leg vein health Under the brand name antistax®, Boehringer
of the described symptoms. antistax® acts to
Ingelheim markets a range of products developed
help keep the fluid that flows out of the capillar
for the prevention and treatment of symptoms
ies at normal levels, even when standing or sit
attributable to known venous insufficiency. The
ting down for a long time. Red vine leaf extract
most common symptoms of venous insufficiency
AS 195, the active ingredient in antistax® prod
observable for consumers are varicose veins,
ucts, works on the endothelium inside the veins
oedema of the lower leg, heavy or tired legs, sen
by sealing them from the inside, thereby reduc-
sation of tension, tingling and pain. antistax®
ing the swelling and the sensation of pain and
capsules and tablets are scientifically proven to
heaviness.
help maintain healthy leg vein circulation. Products available in the antistax® range Heavy, aching and tired legs often occur after
include antistax® tablets, antistax® capsules,
long periods of standing or sitting, and increase
antistax® cooling gel and antistax® cooling
at the end of the day or during the summer when
spray.
outdoor temperatures rise. antistax® tablets and antistax® capsules offer effective treatment
Pain The brand thomapyrin® comprises products
For this reason, the triple combination is recom
for the treatment of acute pain of mild to inter
mended by many national and international
mediate intensity.
medical societies as first choice acute treatment
thomapyrin® classic is the core product,
thomapyrin® is positioned as the expert treat
which is composed of a triple combination of ace-
ment of headache. Several line extensions are
tylic salicylic acid, paracetamol and caffeine. The
available: thomapyrin® classic for normal
three components suppress pain synergistically
headache, thomapyrin® intensiv for stronger
via interaction with several pain-related molec
headache, thomapyrin® medium for milder
ular mechanisms. As a result thomapyrin®
headache, and thomapyrin® Effervescent as a
c lassic disposes of a fast and superior efficacy
galenic alternative.
for tension type headache and migraine.
compared with its single components which is, amongst others, well proven by state-of-the-art clinical studies.
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product portfolio
Indications
Brand names
Active ingredients
• Chronic venous insufficiency
antistax®
red vine leaf extract
Indications
Brand names
Active ingredients
• Pain
thomapyrin® classic thomapyrin® intensiv (*)
acetylsalicylic acid, paracetamol, caffeine
* only available in Germany
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Samples of the product portfolio Consumer Health Care
Prevention and treatment of symptoms of chronic venous insufficiency; varicose veins, leg oedema, painful swollen legs, tingling legs, tired and heavy legs.
For adults and adolescents older than twelve years for acute treatment of mild to moderate headache, migraine attacks, with and without aura, and for the treatment of tension-type headache.
Samples of the product portfolio Animal Health Food producing animals – Swine Infectious respiratory diseases
Pain and inflammatory diseases
ingelvac c ircoflex® is the first one-dose
metacam® as a member of the class of non-
vaccine for the reduction of the early and late
steroidal anti-inflammatory drugs (NSAID)
form of porcine circovirus disease (PCVD). This
marries the need for maintained profitability and
vaccine provides significant reduction of mortal
the concern for animal welfare in animal pro
ity in the acute phase of PCVD as well as improved
duction.
growth rates in the chronic phase of the disease. ingelvac circoflex® protects without causing
Due to its long-acting feature and its outstanding
systemic adverse reactions or injection site
efficacy in controlling inflammatory symptoms,
swellings. ingelvac® prrs mlv is licensed for
it helps minimising losses from inflammation
the active immunisation against the respiratory
and maintaining profitability in disease situ
and reproductive form of porcine reproductive
ations. At the same time, metacam® effectively
and respiratory syndrome (PRRS).
controls pain and supports the restoration of the well-being in farm animals. The use of m etacam®
ingelvac® m. hyo and ingelvac mycoflex®
is convenient and inflicts no stress on animals
are licensed for the active immunisation of pigs
due to its low-volume, one-shot feature.
against enzootic pneumonia (EP) in a one-dose regimen. Through their advanced depot-adju
metacam® is licensed for the use in swine
vant systems they provide a long lasting and
suffering from non-infectious locomotor dis
effective protection until slaughter, proven even
orders. In addition, it is used in the treatment of
in high-challenge situations.
puerperal septicaemia and toxaemia (mastitismetritis-agalactia syndrome).
Infectious enteric diseases enterisol® ileitis is the first and only vaccine against ileitis caused by Lawsonia intracellularis. It is licensed to improve weight gain and to reduce growth variability associated with the disease. enterisol® ileitis helps to reduce the total antimicrobial use in pork production.
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product portfolio
Indications
Brand names
Active ingredients
• Infectious respiratory diseases
ingelvac circoflex®
recombinant vaccine (porcine circovirus type 2, PCV-2)
For the active immunisation of pigs over the age of two weeks against porcine circovirus type 2 to reduce mortality, clinical signs – including weight loss – and lesions in lymphoid tissues associated with porcine circovirus diseases (PCVD).
• Infectious respiratory diseases
ingelvac® m.hyo
inactivated vaccine (Mycoplasma hyopneumoniae)
For the active immunisation of pigs from three weeks of age to reduce lung lesions following infection with Mycoplasma hyopneumoniae.
• Infectious respiratory diseases
ingelvac® prrs mlv
attenuated live vaccine (PRRS virus)
For the active immunisation of swine from three weeks of age against the respiratory and reproductive form of PRRS virus infection (porcine reproductive and respiratory syndrome).
• Infectious enteric diseases
enterisol® ileitis
attenuated live vaccine (Lawsonia intracellularis)
For active immunisation of pigs from three weeks of age and older to reduce intestinal lesions caused by Lawsonia intracellularis infection and to reduce growth variability and loss of weight gain associated with the disease.
• Pain and inflammatory diseases
metacam®
meloxicam
Non-infectious locomotor disorders. To reduce lameness and inflammation. Adjunctive therapy against mastitismetritis-agalactia-syndrome.
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Samples of the product portfolio Animal Health
Food producing animals – Cattle Mastitis
Pain and inflammatory diseases
mamyzin® Injection contains penethamate
metacam® as a member of the class of non-ster
hydroiodide, a prodrug of penicillin G which
oidal anti-inflammatory drugs (NSAIDs) com
offers a unique pharmacokinetic profile.
bines the need for maintained profitability and the concern for animal welfare in animal pro
Achieving very high absorption and accumula
duction.
tion rates of its active principle in the udder, mamyzin® is an excellent first line treatment of
Due to its long-acting feature and its outstanding
(penase negative) Staphylococcus aureus and
efficacy in controlling inflammatory symptoms,
Streptococcus spp. Highly suitable for combin
it helps minimising losses from inflammation
ation therapy, mamyzin® is aditionally an ideal
and maintaining profitability in animals suffer
tool in whole herd sanitation programmes where
ing from disease. At the same time metacam®
it is used to control subclinical mastitis during
effectively controls pain and supports the restor
lactation, as initial dry-off treatment in problem
ation of the well-being in farm animals. The use
herds, and for metaphylaxis in heifers.
of metacam® is convenient and inflicts no stress
benestermycin® is a broad spectrum and long-
feature.
on animals due to its low-volume, one-shot acting antibiotic preparation designed to effec tively treat existing infections at dry-off and to
metacam® is licensed for use in cattle suffering
prevent new infections during the dry period in
from respiratory disease. Also, it is indicated in
dairy cattle.
calves affected by diarrhoea and as adjunctive therapy in the treatment of mastitis in lactating
ubrolexin® delivers enhanced bactericidal activity through a specifically designed combina tion of two complementary targeted antibiotics working in synergy. ubrolexin® marks a new quality of broad spectrum mastitis treatment because it achieves uncompromised efficacy on both ends of the pathogen spectrum. This makes ubrolexin® a simple-to-use, “no compromise” product for the routine treatment of clinical mastitis.
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cattle.
product portfolio
Indications
Brand names
Active ingredients
• Mastitis
mamyzin®
penethamate hydroiodide
For the treatment of mastitis in dairy cows caused by Gram-positive pathogens.
• Mastitis
benestermycin®
penethamate hydriodide benethamine penicillin framycetin sulphate
To dry out the clinical healthy udders of milking cows when required for the udder health of the stock.
• Mastitis
ubrolexin®
cefalexin (as monohydrate), kanamycin (as monosulphate)
Treatment of clinical mastitis in lactating dairy cows for bacteria susceptible to the combination of cefalexin and kanamycin such as Staphylococcus aureus, Streptococ cus dysgalactiae, Streptococcus uberis and Escherichia coli.
• Infectious respiratory diseases
express® (*)
For prevention of reproductive and attenuated live and inactivated vaccines (IBRV, BVDV, PI3V, BRSV, respiratory diseases in cattle. C. fetus and Lepto spp.)
*only available in Canada and USA
• Pain and inflammatory diseases
metacam®
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meloxicam
Samples of the product portfolio Animal Health
Acute respiratory infection with appropriate antibiotic therapy, diarrhoea in combination with oral rehydration therapy, adjunctive therapy of acute mastitis in combination with antibiotic therapy.
Companion animals – Small animals The main small animals products of Boehringer
heart muscle, helping it to beat stronger and
Ingelheim Animal Health address major chronic
pump blood more efficiently.
diseases: heart failure and osteoarthritis. metacam® is a non-steroidal anti-inflammatory As the first of a new class of heart treatments
drug (NSAID). It is available as oral suspension,
termed inodilators, vetmedin® has been shown
tablets and injectable solution for dogs and as
to significantly improve the clinical signs and
oral suspension and injectable solution for cats.
extend the life expectancy in dogs with conges
The indications include the alleviation of inflam
tive heart failure. vetmedin® works through
mation and pain in chronic musculoskeletal
two complementary modes of action; it opens up
disorders and the reduction of post-operative
the blood vessels taking blood to and away from
pain in dogs and cats. The variety of formula
the heart, thereby lowering the pressure on the
tions offers veterinarians and owners the flexi
heart and reducing the work the heart has to do
bility to use the formulations they prefer to
to pump blood around the dog’s body. At the
manage the various levels of inflammation and
same time, vetmedin® has a direct effect on the
pain associated with the licensed indications.
Companion animals – Horse The main horse products of Boehringer Ingel
metacam® is indicated for the alleviation of
heim Animal Health focus on the therapeutic
inflammation and relief of pain in both acute and
areas respiratory disease, lameness and colic.
chronic musculoskeletal disorders in horses. It is available as oral suspension and as solution
ventipulmin® is a treatment of acute and
for injection. The solution for injection is also
chronic respiratory disease where airway ob
indicated for the relief of pain associated with
struction due to bronchospasm and/or mucus
equine colic, complementing buscopan® com
accumulation is a contributing factor and
positum.
improved mucociliary clearance is desirable. ventipulmin® can be used alone or as adjunc
In North America there is also a comprehensive
tive therapy in chronic obstructive pulmonary
range of equine vaccines available.
disease (COPD) and in acute, sub-acute and chronic respiratory allergic conditions.
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product portfolio
Indications
Brand names
Active ingredients
• Congestive heart failure
vetmedin®
pimobendan
For the treatment of congestive heart failure in dogs.
• Pain and inflammatory diseases
metacam®
meloxicam
Dog, cat: alleviation of inflammation and pain associated with acute and chronic musculoskeletal disorders. Reduction of post-operative pain and inflammation following orthopaedic and soft tissue surgery.
Indications
Brand names
Active ingredients
• Acute and chronic obstruc tive respiratory diseases
ventipulmin®
clenbuterol
Bronchodilator for the treatment of acute, sub-acute and chronic obstructive airway disease in horses.
• Pain and inflammatory diseases
metacam®
meloxicam
Alleviation of inflammation and relief of pain in both acute and chronic musculoskeletal disorders. Relief of pain associated with colic.
105
Samples of the product portfolio Animal Health
Contents
} Overview of the major consolidated companies } Consolidated balance sheet } Consolidated profit and loss statement } Cash flow statement } Statement of changes in group equity } Notes to the consolidated financial statements } Auditor’s Report
106
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
Consolidated Financial Statements 2008
Overview of the major consolidated companies
C. H. Boehringer Sohn AG & Co. KG* Boehringer Ingelheim GmbH
Boehringer Ingelheim Europe GmbH
Germany
D
P
R
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim Boehringer Ingelheim Vetmedica GmbH, Ingelheim Boehringer Ingelheim microParts GmbH, Dortmund
Austria
D
P
Boehringer Ingelheim International GmbH
R
Boehringer Ingelheim RCV GmbH & Co.KG, Vienna
Forschungsinstitut für Molekulare Pathologie Gesellschaft mbH, Vienna
Boehringer Ingelheim Pharma Ges.m.b.H., Vienna Czech Republic
D
D
Boehringer Ingelheim International Trading (Shanghai) Co. Ltd., Shanghai
China
Boehringer Ingelheim Finland Ky, Espoo Norway
D
Boehringer Ingelheim Norway KS, Asker Poland
D
Belgium
SCS Boehringer Ingelheim Comm. V., Brussels
Boehringer Ingelheim s.r.o., Prague Finland
R
Austria
D
Boehringer Ingelheim Sp.zo.o., Warsaw
D
Boehringer Ingelheim Shanghai Pharmaceuticals Co. Ltd., Shanghai D
Philippines
Boehringer Ingelheim (Phil.), Inc., Manila South Korea
D
Boehringer Ingelheim Korea Ltd., Seoul Boehringer Ingelheim Vetmedica Korea Ltd., Seoul
D Distribution P
Production
R Research
*sole general partner: Boehringer AG
108
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
P
P
C. H. Boehringer Sohn Grundstücksverwaltung GmbH & Co. KG Boehringer Ingelheim Auslandsbeteiligungs GmbH
D
Argentina
Boehringer Ingelheim S.A., Buenos Aires D
Boehringer Ingelheim Pty. Ltd., North Ryde D
P
Boehringer Ingelheim do Brasil Quimica e Farmaceutica Ltda., São Paulo Solana Agro Pecuaria Ltda., Arapongas Canada
R
D
D
Boehringer Ingelheim Ltda., Santiago de Chile D
P
D
P
Boehringer Ingelheim Danmark A/S, Copenhagen D
Ecuador
Boehringer Ingelheim del Ecuador Cia. Ltda., Quito
R
D
P
D
P
R
Boehringer Ingelheim Vetmedica Japan Co. Ltd., Kawanishi Boehringer Ingelheim Seiyaku Co. Ltd., Yamagata D
P
D
Boehringer Ingelheim Promeco S.A. de C.V., Mexico City
Boehringer Ingelheim Ellas AE, Athens
109
D
D
P
Boehringer Ingelheim USA Corporation, Ridgefield, Connecticut Ben Venue Laboratories, Inc., Bedford, Ohio Roxane Laboratories, Inc., Columbus, Ohio
Boehringer Ingelheim S.A., Barcelona Europharma S.A., Barcelona
Boehringer Ingelheim Vetmedica, Inc., St. Joseph, Missouri
Laboratorios Fher S.A., Barcelona
Boehringer Ingelheim Roxane, Inc., Columbus, Ohio D
Boehringer Ingelheim AB, Stockholm D
P
Boehringer Ingelheim (Schweiz) GmbH, Basel Pharmaton S.A., Lugano D
Taiwan D
Boehringer Ingelheim Taiwan Ltd., Taipei
D
Boehringer Ingelheim (Thai) Ltd., Bangkok
Boehringer Ingelheim B. V., Alkmaar
R
Boehringer Ingelheim España S.A., Barcelona
Switzerland
Boehringer Ingelheim Vetmedica S.A. de C.V., Guadalajara
Boehringer Ingelheim (N.Z.) Ltd., Auckland P
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut
Sweden R
P
Unilfarma Lda., Lisbon
Spain
Nippon Boehringer Ingelheim Co. Ltd., Tokyo
D
Boehringer Ingelheim Corp., Ridgefield, Connecticut
Ingelheim Pharmaceuticals (Pty.) Ltd., Randburg
Istituto De Angeli srl, Reggello
USA
Boehringer Ingelheim Lda., Lisbon
South Africa
Bidachem S.p.A., Fornovo S. Giovanni
New Zealand
Labso Chimie Fine S.A.R.L., Blanquefort
D
Portugal
Boehringer Ingelheim (Pty.) Ltd., Randburg
Netherlands
Boehringer Ingelheim France S.A.S., Paris
Greece
P
Boehringer Ingelheim Italia S.p.A., Reggello
Mexico
Boehringer Ingelheim S.A., Bogotá
France
D
SSP Co. Ltd., Tokyo (61%)
Chile
Denmark
Italy
Japan
Boehringer Ingelheim (Canada) Ltd., Burlington
Colombia
P
PT Boehringer Ingelheim Indonesia, Jakarta
Australia
Brazil
D
Indonesia
D
Thailand
D
Turkey
Boehringer Ingelheim Ilac Ticaret A.S., Istanbul United Kingdom
D
Boehringer Ingelheim Ltd., Bracknell
Overview of the major consolidated companies
P
Boehringer Ingelheim Chemicals, Inc., Petersburg, Virginia Venezuela
Boehringer Ingelheim C.A., Caracas
D
C. H. Boehringer Sohn AG & Co. KG, Ingelheim Consolidated balance sheet Assets (in millions of EUR)
Notes1)
Intangible assets
(3.1)
Tangible assets
(3.2)
3,177
2,972
Financial assets
(3.3)
1,739
1,638
Fixed assets
31.12.2008
31.12.2007
539
547
5,455
5,157
Inventories
(3.4)
1,561
1,387
Accounts receivable
(3.5)
2,659
2,165
Securities
517
162
Cash and cash equivalents
795
853
Current assets
5,532
4,567
Deferred taxes
766
691
Deferred charges and prepaid expenses Total assets
Liabilities and equity (in millions of EUR)
Notes1)
Shareholders’ capital Group reserves Balance sheet currency conversion difference
71
56
11,824
10,471
31.12.2008
31.12.2007
178
178
3,326
1,670
-225
-285
Net income
1,424
1,809
Equity
4,703
3,372
190
167
4,893
3,539
Minority interests Group equity Provisions
(3.6)
4,952
4,567
Accounts payable
(3.7)
1,761
2,151
6,713
6,718
168
159
Liabilities Deferred taxes Deferred charges Total liabilities and equity
1)
For explanation, see relevant section in the notes to the consolidated financial statements.
110
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
50
55
11,824
10,471
consolidated financial statements
C. H. Boehringer Sohn AG & Co. KG, Ingelheim Consolidated profit and loss statement (in millions of EUR)
Notes1)
Net sales
(4.1)
Changes in inventories Other internal work performed and capitalised Other operating income Total revenues
2008
2007
11,595
10,952
59
89
4
4
690
539
12,348
11,584
Material costs
(4.2)
-1,642
-1,627
Personnel costs
(4.3)
-3,004
-2,886
Amortisation of intangible and depreciation of tangible assets
(4.4)
-524
-504
Other operating expenses
(4.5)
-5,198
-4,467
1,980
2,100
Operating income Financial income
(4.6)
-40
262
Holding income
(4.7)
-7
0
1,933
2,362
-505
-550
1,428
1,812
-4
-3
1,424
1,809
Income before taxes Taxes2)
(4.8)
Income after taxes Third-party share Net income
1)
(4.9)
For explanation, see relevant section in the Notes to the Consolidated Financial Statements. Due to legal requirements the disclosure of the shareholder’s personal taxes arising from consolidated business activities as tax expenses is not allowed. These taxes are shown as withdrawals from the accrued group capital.
2)
111
Consolidated balance sheet / Consolidated profit and loss statement
C. H. Boehringer Sohn AG & Co. KG, Ingelheim Cash flow statement 2008
2007
1,428
1,812
532
508
37
72
1,997
2,392
Change in other provisions
268
172
Other non-cash income and expenses
-20
-13
Loss/gain on disposals of fixed assets
63
8
Change in inventories
-162
-164
Change in accounts receivable and other assets not related to investing or financing activities
-317
24
(in millions of EUR) Income after taxes Write-downs/write-ups on fixed assets
1)
Change in provisions for pensions Cash flow
Change in trade accounts payable and other liabilities not related to investing or financing activities Cash flow from operating activities Investments in intangible assets
72
-77
1,901
2,342
-43
-98
-665
-654
Investments in non-current financial assets1)
-51
-35
Proceeds from disposals of intangible assets
0
0
Proceeds from disposals of property, plant and equipment
21
23
Proceeds from disposals of non-current financial assets1)
7
7
Cash flow from investing activities
–731
–757
Cash payments to shareholders and minority shareholders
-434
-3,355
Investments in property, plant and equipment
Cash proceeds from borrowings/repayments of loans
-501
442
Cash flow from financing activities
–935
–2,913
235
-1,328
0
0
116
-25
Securities and liquid funds 2) as of 1. 1.
2,581
3,934
Securities and liquid funds as of 31. 12.
2,932
2,581
Change in liquid funds from cash-relevant transactions Changes in liquid funds due to changes in scope of consolidation Changes in liquid funds due to exchange rate movements
2)
1) 2)
excl. fixed-asset securities liquid funds, securities within fixed and current assets (+) = source of funds, (–) = use of funds
112
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
consolidated financial statements
C. H. Boehringer Sohn AG & Co. KG, Ingelheim Statement of changes in group equity
(in millions of EUR) Balance as of 31. 12. 2006
Shareholders’ capital1)
Accrued group capital
of which currency effects
Equity
Minority interests
of which currency effects
Group equity
178
4,997
-140
5,175
188
-51
5,363
Contributions
0
0
0
0
0
0
0
Withdrawals
0
-3,467
0
-3,467
0
0
-3,467
Net income
0
1,809
0
1,809
3
0
1,812
Change of scope of consolidation
0
0
0
0
0
0
0
Other changes
0
-145
-145
-145
-24
-9
-169
178
3,194
-285
3,372
167
-60
3,539
Contributions
Balance as of 31. 12. 2007
0
0
0
0
0
0
0
Withdrawals
0
-154
0
-154
0
0
-154
Net income
0
1,424
0
1,424
4
0
1,428
Change of scope of consolidation
0
0
0
0
0
0
0
Other changes
0
61
60
61
19
51
80
178
4,525
-225
4,703
190
-9
4,893
Balance as of 31. 12. 2008
T he shareholders’ capital consists of the equity of C. H. Boehringer Sohn AG & Co. KG and C. H. Boehringer Sohn Grundstücksverwaltung GmbH & Co. KG. As of 31.12.2008 the capital consists only of the limited partners. The shareholders’ personal taxes arising from consolidated business activities are shown as withdrawals from the accrued group capital.
1)
113
Cash flow statement / Statement of changes in group equity
C. H. Boehringer Sohn AG & Co. KG, Ingelheim Notes to the consolidated financial statements 1 Principles and methods 1.1 General principles The consolidated financial statements of Boehringer Ingelheim for the fiscal year 2008 have been prepared pursuant to section 264a German Commercial Code (HGB) by applying the group accounting regulations of section 290 to 314 HGB. In accordance with section 297, paragraph 1 HGB, the consolidated financial statements are composed of the consolidated balance sheet, the consolidated profit and loss statement, notes to the consolidated financial statements, the consolidated cash flow statement and the statement on changes in equity. 1.2 Companies included in the consolidation The ultimate parent of the Boehringer Ingelheim group is C. H. Boehringer Sohn AG & Co. KG. Boehringer AG is the sole unlimited managing partner of this company. Besides C. H. Boehringer Sohn AG & Co. KG there is C. H. Boehringer Sohn Grundstücksverwaltung GmbH & Co. KG whose unlimited partner is under the unified management of C. H. Boehringer Sohn AG & Co. KG. The Boehringer Ingelheim group of companies consists of 138 affiliated companies in and outside Germany. In addition to C. H. Boehringer Sohn AG & Co. KG and C. H. Boehringer Sohn Grundstücksverwaltung GmbH & Co. KG, a further 108 companies in which C. H. Boehringer Sohn AG & Co. KG holds directly or indirectly the majority of voting shares are included in the consolidated financial statements. Twenty-six companies were not consolidated in the reporting year, as the net assets, financial position and results of operations of these companies were insignificant to Boehringer Ingelheim. Combined they represent less than 1 % of the group’s net sales, equity and net profit. A further two companies are subject to bylaws containing enduring restrictions. Compared to the previous year, the total number of affiliated companies was increased by three: • one company was liquidated, • four companies were established.
114
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
consolidated financial statements
A separate statement of interests held by Boehringer Ingelheim will be submitted to the authority operating the German Federal Gazette in order to place it in the Register of Companies. The following subsidiaries were exempted from the reporting and disclosure obligations in accordance with section 264, paragraph 3 HGB: • Boehringer Ingelheim GmbH, Ingelheim • Boehringer Ingelheim International GmbH, Ingelheim • Dr. Karl Thomae GmbH, Biberach • Dr. Karl Thomae Wohnungsbau GmbH, Biberach • Boehringer Ingelheim Europe GmbH, Ingelheim • Boehringer Ingelheim Vetmedica GmbH, Ingelheim • Boehringer Ingelheim Secura Versicherungsvermittlungs GmbH, Ingelheim • Boehringer Ingelheim Grundstücks-GmbH, Ingelheim • Boehringer Ingelheim Finanzierungs GmbH, Ingelheim • Boehringer Ingelheim R&D Beteiligungs GmbH, Ingelheim Exempted from reporting and disclosure obligations of annual financial statements according to HGB regulations for joint stock companies under section 264b HGB are: • C. H. Boehringer Sohn AG & Co. KG, Ingelheim • C. H. Boehringer Sohn Grundstücksverwaltung GmbH & Co. KG, Ingelheim • Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim • Boehringer Ingelheim Veterinary Research Center GmbH & Co. KG, Hannover
1.3 Consolidation methods For inventories, accounts receivable and payable, and the income and expense items, business transactions among the consolidated companies were eliminated as part of the debt consolidation, according to section 303 HGB, the elimination of inter-company profits according to section 304 HGB, and the income and expense consolidation according to section 305 HGB. The purchase method of accounting was used for the capital consolidation of those subsidiaries that were included for the first time in the consolidated financial statements. First-time consolidation takes place at the time of the respective company becoming a subsidiary.
115
Notes to the consolidated financial statements
1.4 Currency conversions The financial statements prepared in foreign currencies were translated into euros, the functional currency of the group parent company, C. H. Boehringer Sohn AG & Co. KG, according to the modified closing rate concept. All assets and liabilities have been converted at the year-end rate. The profit and loss statement and, consequently, net income, were converted at the average annual rate for the reporting year. The shareholders’ capital and the group reserves are calculated using historical exchange rates. Translation differences due to the conversion of foreign currencies are shown as a balancing item in the equity without impact on income. In general the functional currency of subsidiaries is the respective local currency. Annual financial statements in high inflation countries are in principle drawn up in accordance with German Accounting Standard 14 (GAS 14); in the financial year 2008, no group company was affected by high inflation accounting. The most important currencies for Boehringer Ingelheim reflect the following changes in the reporting year (base 1 euro): year-end rate 31.12.2008
US dollar Japanese yen
average annual rate
31.12.2007
2008
2007
1.39
1.47
1.47
1.37
126.14
164.93
152.27
161.24
Pound sterling
0.95
0.73
0.79
0.68
Canadian dollar
1.69
1.44
1.55
1.47
116
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
consolidated financial statements
2 Accounting and evaluation methods 2.1 Fixed assets Intangible and tangible assets are shown at purchase or manufacturing cost, net of regular straight-line depreciation, according to the technical and economic situation. The following periods of use were applied: Intangible assets
3 to 15 years
Buildings
20 years
Technical facilities and machinery Other facilities, operating and business equipment
10 years 3 to 10 years
In the consolidated financial statements the standard method of depreciation is the straight-line method. Anticipated long-term losses in the value of investments were accounted for by unscheduled write-offs. Cost of direct material and production as well as appropriate portions of material and production overheads were taken into consideration for the determination of the manufacturing costs. Fully amortised goodwill that is more than five years old, or is materially insignificant, is shown under disposals. All capitalised intangible assets have a limited useful life. Goodwill resulting from the consolidation of the purchase of shares of Boehringer Ingelheim Korea Ltd. and Baiksu Pharmaceutical Co. Ltd. is being amortised according to plan over ten years. Financial assets were valued at the lower of either purchase cost or fair market value. The valuation of securities in case of temporary diminution in value is made at the lower current value.
2.2 Current assets Inventories are valued at the lower of either purchase or manufacturing cost using the weighted average cost flow method as the group-wide uniform method of measurement, or fair market value, whereas C. H. Boehringer Sohn AG & Co. KG applies the LIFO Method in its individual financial statements. The cost of direct material and production as well as appropriate portions of material and production overheads were taken into consideration for the determination of the manufacturing costs. Necessary reductions were made for inventory risks. Accounts receivable were stated at their purchase cost net of any individual valuation allowances required. The general credit risk was covered by a general valuation allowance for bad debt. Other assets, securities and liquid funds were stated at the lower of either purchase cost, present value or fair market value. Short-term foreign currency items were recorded at the year-end rate of exchange.
117
Notes to the consolidated financial statements
2.3 Group reserves Group reserves include the retained earnings of the consolidated subsidiaries from prior years, consolidation entries that affect earnings and credit balances arising from capital consolidation, where they respectively relate to prior years.
2.4 Provisions Provisions include amounts necessary to cover any perceptible obligations and risks that require recognition in the accounts, including provisions for contingent losses from pending contracts. The valuation is made on the basis of reasonable commercial judgement. Provisions with an implied interest are shown on a discounted basis (e. g. certain personnel provisions).
2.5 Liabilities Liabilities are shown in the balance sheet at the repayable amount. Liabilities in foreign currencies were recorded at the year-end rate of exchange.
2.6 Deferred taxes Deferred tax assets and liabilities represent the tax deferral in accordance with sections 274 and 306 HGB, which arise because of temporary differences between the tax balance sheets of the individual companies and the consolidated balance sheet (including differences arising from adjustments for conformity in group-wide reporting and evaluation as well as consolidation measures). Quasi-permanent differences between the consolidated balance sheet and the tax balance sheet are treated as temporary differences in accordance with German Accounting Standard 10 (GAS 10). In the individual balance sheets (i. e. the financial statements II) the consolidated companies made use of their option to capitalise assets to the amount of probable tax relief in the following years in accordance with section 274, paragraph 2 HGB. The calculation of deferred taxes is based on the tax rates that are expected to be valid at the time of their realisation. The capitalisation of deferred tax assets on tax loss carry-forwards is carried out if it is sufficiently probable that the tax benefits can be realised.
118
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
consolidated financial statements
3 Notes to the consolidated balance sheet 3.1 Intangible assets Concessions/ similar rights
Goodwill
Advance payments
Total
Balance as of 1. 1. 2007
975
806
11
1,792
Currency conversion difference
-46
0
0
-46
(in millions of EUR) Procurement/manufacturing costs
Additions due to first consolidation
0
0
0
0
Additions
43
48
7
98
Disposals
-17
-285
0
-302
11
0
-6
5
966
569
12
1,547
27
0
1
28
0
0
0
0
Additions
27
0
16
43
Disposals
-14
0
0
-14
Reclassifications Balance as of 31. 12. 2007 Currency conversion difference Additions due to first consolidation
Reclassifications Balance as of 31. 12. 2008
14
0
-8
6
1,020
569
21
1,610
432
806
0
1,238
-8
0
0
-8
0
0
0
0
65
7
0
72
Accumulated depreciations Balance as of 1. 1. 2007 Currency conversion difference Additions due to first consolidation Additions
Write-ups
0
0
0
0
Disposals
-17
-285
0
-302
Reclassifications
0
0
0
0
472
528
0
1,000
Currency conversion difference
8
-1
0
7
Additions due to first consolidation
0
0
0
0
Additions
67
5
0
72
Write-ups
0
0
0
0
Disposals
-8
0
0
-8
0
0
0
0
Balance as of 31. 12. 2008
539
532
0
1,071
Book value as of 31. 12. 2007
494
41
12
547
Book value as of 31. 12. 2008
481
37
21
539
Balance as of 31. 12. 2007
Reclassifications
119
Notes to the consolidated financial statements
3.2 Tangible assets Land and buildings
(in millions of EUR)
Technical facilities and machines
Procurement/manufacturing costs Balance as of 1. 1. 2007 Currency conversion difference Additions due to first consolidation
Other Advance facilities/ payments/ operating construction equipment in progress
Total
2,110
2,238
1,590
375
6,313
-80
-64
-52
-21
-217
0
0
0
0
0
Additions
75
97
158
324
654
Disposals
-17
-47
-98
-5
-167
Reclassifications Balance as of 31. 12. 2007 Currency conversion difference Additions due to first consolidation
89
98
66
-258
-5
2,177
2,322
1,664
415
6,578
97
32
10
18
157
0
0
0
0
0
Additions
62
113
149
341
665
Disposals
-68
-107
-88
-6
-269
89
76
38
-209
-6
2,357
2,436
1,773
559
7,125
1,076
1,277
1,074
0
3,427
-39
-37
-36
0
-112
0
0
0
0
0
Additions
83
176
173
0
432
Write-ups
0
-1
0
0
-1
Disposals
-11
-43
-86
0
-140
0
-7
7
0
0
1,109
1,365
1,132
0
3,606
55
16
9
0
80
Reclassifications Balance as of 31. 12. 2008
Accumulated depreciations Balance as of 1. 1. 2007 Currency conversion difference Additions due to first consolidation
Reclassifications Balance as of 31. 12. 2007 Currency conversion difference Additions due to first consolidation Additions
0
0
0
0
0
93
182
178
0
453
Write-ups
0
0
0
0
0
Disposals
-31
-82
-78
0
-191
Reclassifications
0
0
0
0
0
Balance as of 31. 12. 2008
1,226
1,481
1,241
0
3,948
Book value as of 31. 12. 2007
1,068
957
532
415
2,972
Book value as of 31. 12. 2008
1,131
955
532
559
3,177
120
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
consolidated financial statements
3.3 Financial assets Investments in affiliated companies
Loans to affiliated companies
Investments in related companies
Loans to related companies
Investment securities
Other loans
Total
Balance as of 1. 1. 2007
18
8
10
6
3,039
23
3,104
Currency conversion difference
-1
0
0
0
-5
0
-6
Additions due to first consolidation
0
0
0
0
0
0
0
Additions
1
0
30
0
257
4
292
Disposals
-6
-1
0
-3
-1,672
-7
-1,689
0
0
0
0
0
0
0
12
7
40
3
1,619
20
1,701
7
2
-1
0
10
0
18
(in millions of EUR) Procurement/manufacturing costs
Reclassifications Balance as of 31. 12. 2007 Currency conversion difference
0
0
0
0
0
0
0
Additions
Additions due to first consolidation
17
0
29
0
175
5
226
Disposals
0
-1
-1
0
-141
-6
-149
Reclassifications
0
0
0
0
0
0
0
36
8
67
3
1,663
19
1,796
Balance as of 1. 1. 2007
3
0
2
3
50
3
61
Currency conversion difference
0
0
0
0
0
0
0
Additions due to first consolidation
0
0
0
0
0
0
0
Additions
0
0
5
0
12
0
17
Write-ups
0
0
0
0
-2
0
-2
Disposals
Balance as of 31. 12. 2008
Accumulated depreciations
-3
0
0
-3
-7
0
-13
Reclassifications
0
0
0
0
0
0
0
Balance as of 31. 12. 2007
0
0
7
0
53
3
63
Currency conversion difference
0
0
-1
0
0
-1
-2
Additions due to first consolidation
0
0
0
0
0
0
0
Additions
0
0
7
0
31
0
38
Write-ups
0
0
0
0
-37
0
-37
Disposals
0
0
-1
0
-4
0
-5
Reclassifications
0
0
0
0
0
0
0
Balance as of 31. 12. 2008
0
0
12
0
43
2
57
Book value as of 31. 12. 2007
12
7
33
3
1,566
17
1,638
Book value as of 31. 12. 2008
36
8
55
3
1,620
17
1,739
As in the previous year, the item other loans includes no loans to shareholders.
121
Notes to the consolidated financial statements
3.4 Inventories (in millions of EUR)
31.12.2008
31.12.2007
350
242
Unfinished products
624
598
Finished products and goods for resale
576
540
11
7
1,561
1,387
Raw materials and supplies
Advance payments to suppliers
3.5 Accounts receivable (in millions of EUR) Trade accounts receivable Receivables from affiliated companies Receivables from related companies Other assets
31.12.2008
Residual term over 1 year
31.12.2007
Residual term over 1 year
1,977
4
1,797
6
4
0
3
0
6
0
3
0
672
23
362
20
2,659
27
2,165
26
The item other assets contains receivables from shareholders amounting to EUR 189 million (2007: EUR 1 million).
3.6 Provisions (in millions of EUR)
31.12.2008
31.12.2007
Pension provisions
2,170
2,110
Tax provisions Other provisions
122
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
492
486
2,290
1,971
4,952
4,567
consolidated financial statements
Pension provisions Boehringer Ingelheim’s pension schemes are based on various defined contribution plans as well as defined benefit plans. Pension obligations arising from direct or indirect defined benefit plans are determined on the basis of actuarial calculations in accordance with the projected unit credit method, taking future salary and pension increases into consideration. The actuarial calculation of the pension obligation from defined benefit plans is based on countryspecific biometric data (e. g. in Germany the “generation tables” issued in 2005 by Professor Klaus Heubeck) and actuarial assumptions. The main countries applied the following parameters: Germany
Parameter (in % as of 31 December)
USA
Japan
2008
2007
2008
2007
2008
2007
Discount rate
5.3
5.3
5.8
5.8
1.5
1.5
Expected return on plan assets
6.0
6.0
8.0
8.0
2.2–3.0
2.2–3.0
Salary increase
4.0
4.0
5.5
5.5
0.0–3.0
0.0–3.0
Pension increase
2.0
2.0
3.0
3.0
0.0
0.0
At the balance sheet date, the present value of the expected pension obligation was netted with the fair value of the respective pension plan assets (funded status). Based on this, pension provisions are determined by deducting unrealised transition amounts as well as unrealised actuarial gains and losses from the funded status. Actuarial gains and losses, inasmuch as they surpass 10 % of the higher value of either the present value of the expected pension obligation or the fair value of the plan assets, are to be spread over the expected average service period of the active employees. On the balance sheet date, pension commitments (including total unrealised transition amounts and actuarial gains and losses) amounted to EUR 594 million (2007: EUR 332 million). Further pension commitments did not exist at year-end. In conjunction with defined contribution plans, group companies paid contributions to state or private insurers on the basis of legal or contractual regulations. On payment of the contributions the companies no longer have any performance obligations. Contributions are recognised as personnel costs.
123
Notes to the consolidated financial statements
3.7 Accounts payable Residual term less than 1 year
Residual term 1–5 years
Residual term over 5 years
31.12.2008
174
117
17
308
800
649
1,239
5
209
1,453
1,351
1,185
751
1
0
752
704
702
29
0
31
60
68
32
0
0
0
0
5
5
– Accounts payable to affiliated companies
12
0
0
12
11
11
– Accounts payable to related companies
1
0
0
1
1
1
(in millions of EUR) Bank loans Other accounts payable of which: – Trade accounts payable – Advance payments – Notes payable
– Other liabilities *
Residual term 31.12.2007 less than 1 year
446
4
178
628
562
434
1,413
122
226
1,761
2,151
1,834
31
39
2
8
*of which: – taxes – social security contributions
There were no liabilities secured by mortgages or similar rights on the balance sheet date consistent with the previous year. At year-end liabilities due to shareholders amounted to EUR 3 million (2007: EUR 64 million).
124
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
consolidated financial statements
4 Notes to the consolidated profit and loss statement The consolidated profit and loss statement is presented in line with the total cost method. 4.1 Net sales by business and business segment (in millions of EUR) Human Pharmaceuticals
2008
2007
11,128
10,544
of which:
Prescription Medicines
9,111
8,660
Consumer Health Care
1,190
1,141
Industrial Customer
819
739
Other sales
8
4
467
408
11,595
10,952
by geographic region (in millions of EUR)
2008
2007
Europe
3,877
3,578
Animal Health
of which: Germany Americas
980
853
5,560
5,463
of which: USA/Canada/Mexico
5,107
5,050
Asia/Australasia/Africa
2,158
1,911
of which: Japan
1,338
1,193
11,595
10,952
(in millions of EUR)
2008
2007
Costs of raw material, supplies and goods for resale
1,287
1,314
355
313
1,642
1,627
(in millions of EUR)
2008
2007
Salaries and wages
2,411
2,291
Social benefits and retirement benefits
593
595
of which: retirement benefits
185
197
3,004
2,886
4.2 Material costs
Expenditure on services
4.3 Personnel costs
125
Notes to the consolidated financial statements
The interest component with respect to the increase in pensions and similar obligations is included in financial income rather than in personnel costs and is, therefore, not included in the operating result of the company.
Average headcount Production Administration Marketing and sales Research and development Apprentices
2008
2007
12,600
12,502
5,299
5,095
15,909
15,095
6,788
6,405
704
703
41,300
39,800
4.4 Amortisation of intangible and depreciation of tangible assets The amortisation of intangible assets and depreciation of tangible assets include unscheduled write-offs of EUR 6 million (2007: EUR 8 million).
4.5 Other operating expenses Other operating expenses include third-party services in research, development, medicine, and marketing, further administration costs, fees, contributions, non-income-related taxes, commissions, rents, freight costs, and expenses for third-party repairs as well as expenses incurred by restructuring measures.
4.6 Financial income (in millions of EUR)
2008
2007
Interest expense relating to pensions and similar obligations
-121
-107
Other interest expense and similar expenditure Interest expense and similar expenditure
-85
-51
-206
-158
Amortisation of other financial assets and short-term investments
-32
-13
Income from other investment securities and from long-term loans
96
346
Other interest income and similar proceeds
126
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
102
87
-40
262
consolidated financial statements
4.7 Holding income 2008
2007
0
5
-7
-5
-7
0
2008
2007
Income taxes
539
554
Deferred taxes
-34
-4
505
550
(in millions of EUR) Gains from the sale of investments Amortisation of financial assets
4.8 Taxes (in millions of EUR)
By concluding profit transfer agreements, significant German companies have since 1 January 2004 belonged to the trade and corporate taxation group of integrated companies of the parent company C. H. Boehringer Sohn AG & Co. KG. As income tax levied on taxable income allocated to the shareholders of C. H. Boehringer Sohn AG & Co. KG may not be shown in the consolidated profit and loss statement, only the trade tax of the relevant companies is shown as a tax expense. In the effective tax-rate reconciliation the expected tax expense for Boehringer Ingelheim is calculated on the profit tax rate for corporations (corporate tax, solidarity levy and trade tax). As in the profit and loss statement tax expenses related to the income tax for partnerships and integrated companies of C. H. Boehringer Sohn AG & Co. KG are limited to showing trade tax, the expected tax expense in the effective tax-rate reconciliation is in this respect adjusted for fictive current and deferred corporate tax expenses in order to link to the profit tax expense shown in the profit and loss statement. This elimination of fictive corporate tax (including the solidarity levy) is shown in the items Fictive Corporation.
127
Notes to the consolidated financial statements
The expected tax expense derived by using a fictive tax rate of 27.5 % (average tax rate for a German corporation at a municipal trade tax levy rate of 332 %; 2007: 340 %) can be reconciled to the actual tax expense as follows: (in millions of EUR) Income before taxes
2008
2007
1,933
Expected tax expense (current and deferred)
532
Decrease/increase in expected tax expense by – Fictive Corporation current taxes
2,362 27.5 %
876
37.1 %
-136
-7.0 %
-317
-13.4 %
– Fictive Corporation deferred taxes
-16
-0.8 %
-25
-1.1 %
– Local tax rate divergences
110
5.7 %
-72
-3.0 %
– Non-taxable income
-25
-1.3 %
-54
-2.3 %
– Non-tax-deductible expenses
10
0.5 %
58
2.5 %
– Taxes related to prior periods
-8
-0.4 %
2
0.1 %
1
0.1 %
2
0.1 %
22
1.1 %
83
3.5 %
8
0.4 %
7
0.3 %
-46
-2.4 %
-52
-2.2 %
53
2.7 %
42
1.7 %
505
26.1 %
550
23.3 %
– Amortisation of goodwill – Changes in applicable tax rates – Withholding taxes not subject to tax credits – Tax credits for research activities – Other effects Actual tax expense (current and deferred)
The deferred taxes can be attributed to the following balance sheet items: 31.12.2008
(in millions of EUR)
31.12.2007
Assets
Liabilities
Assets
Liabilities
Intangible assets
20
2
7
2
Tangible assets
33
105
29
90
Financial assets
15
19
22
17
Inventories
116
14
106
14
Receivables
17
14
19
11
Provisions
529
14
469
24
Liabilities
25
0
23
1
Tax loss carryforwards and tax credits
128
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
11
0
16
0
766
168
691
159
consolidated financial statements
Other disclosure requirements according to GAS 10.39: (in millions of EUR) Deferred tax expense from changes in law Deferred tax expense relating to the write-off of deferred tax assets in fiscal year
2008
2007
22
83
2
1
The absence of changes in accounting and evaluation methods results, as in the previous year, in no deferred tax income. The valuation allowances relating to deferred tax assets amount to EUR 5 million. Unused tax loss carryforwards, on which no deferred tax assets are recognised in the balance sheet, amount to EUR 21 million at year-end, of which EUR 11 million expire in five years and EUR 3 million expire in 10 years at the latest.
4.9 Net income Net income for the year 2008 includes operating income unrelated to the accounting period (mainly the release of other provisions) in the amount of EUR 135 million (2007: EUR 125 million). Operating expenditure unrelated to the accounting period amounted to EUR 66 million (2007: EUR 53 million).
5 Notes to the cash flow statement The cash flow statement shows how the total liquid funds (liquid assets and securities in fixed and current assets) of the Boehringer Ingelheim group have changed during the reporting year through inflow and outflow of cash and cash equivalents. In accordance with German Accounting Standard No. 2 (GAS 2), Cash Flow Statements, cash flows are classified by operating, investing or financing activities. Changes reported by consolidated companies are converted at the average annual rate. Liquid funds are converted, as shown in the balance sheet, according to the year-end rate method. The influence of exchange rate changes on liquid funds is provided separately.
129
Notes to the consolidated financial statements
6 Other information 6.1 Derivative financial instruments Boehringer Ingelheim is, due to its extensive international structure, highly dependent on developments in the major world currencies and interest rates. In order to hedge against the risks, particularly those inherent in supplies and services and financial funding, use is generally made of foreign exchange forward contracts in the case of currency risks. Regarding interest rate risks, use is made of interest rate swaps and interest rate options. The use of derivative financial instruments and the organisational procedure are laid down in internal guidelines. Trade, processing, documentation, and control are kept strictly separate. The risk positions are recorded, analysed and assessed regularly in a special consolidated financial report. The items are periodically re-evaluated and monitored. The fair market value of derivative financial instruments on the balance sheet date is determined by taking year-end market data into consideration while applying prevailing evaluation methods (foreign exchange forward contracts and interest swaps with the net present value method, foreign exchange options and interest options with accredited option pricing models). Foreign exchange options and interest options are recorded at the lower of fair market value or paid or received option premium. They will be taken out of the books at their respective expiry date. Derivative financial instruments at year-end were as follows: Nominal value
(in millions of EUR)
Market value
31.12.2008
31.12.2007
31.12.2008
31.12.2007
Foreign exchange forward contracts
2,562
1,871
51
49
Foreign exchange options
1,126
1,217
-13
90
201
157
0
0
9
21
0
0
Interest options Interest swaps
In sum, the foreign exchange forward contracts recorded positive fair market values on the balance sheet date in the amount of EUR 51 million. A provision, which has been included in other provisions and accruals, was set up for those open items with a negative fair market value within one currency on the balance sheet date. As far as a positive balance of the open items resulted within one currency, this was not applied in accordance with the imparity principle.
130
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
consolidated financial statements
The foreign exchange option contracts recorded negative fair market values on the balance sheet date in the amount of EUR 13 million. The purchased foreign exchange options are shown in other assets. The sold foreign exchange options are recorded in other liabilities.
6.2 Contingent liabilities to the benefit of third parties (in millions of EUR)
31.12.2008
31.12.2007
24
19
31.12.2008
31.12.2007
966
1,192
Liabilities from guarantees, guarantees for bills and cheques, warranties and provisions of collateral for third-party liabilities
6.3 Other financial obligations (in millions of EUR) To third parties
At year-end, other financial obligations included capital investments of EUR 603 million (2007: EUR 657 million). Furthermore, EUR 245 million (2007: EUR 196 million) from renting and leasing contracts are included, of which EUR 70 million (2007: EUR 75 million) concern long-term rent contracts with subsidiaries not included in the consolidation.
6.4 Research and development expenses (in millions of EUR)
2008
2007
Expenses for research and development
2,109
1,900
Starting with reporting year 2008, phase IV clinical trial costs, among others, are included in the expenses for research and development. The figure for 2007 was adjusted accordingly.
131
Notes to the consolidated financial statements
Auditor’s Report We have audited the consolidated financial
We conducted our audit of the consolidated
statements prepared by C. H. Boehringer Sohn
financial statements in accordance with §317
AG & Co. KG, Ingelheim – comprising the
HGB (German Commercial Code) and German
balance sheet, the income statement, statement
generally accepted standards for the audit of
of changes in equity, cash flow statement and
financial statements promulgated by the Institut
the notes to the consolidated financial state-
der Wirtschaftsprüfer (Institute of Public
ments – together with the group management
Auditors in Germany) (IDW). Those standards
report for the business year from 1 January
require that we plan and perform the audit such
to 31 December 2008. The preparation of the
that misstatements materially affecting the
consolidated financial statements and the group
presentation of the net assets, financial position
management report in accordance with German
and results of operations in the consolidated
commercial law is the responsibility of the
financial statements in accordance with
Managing Directors of the managing corporate
(German) principles of proper accounting and
general partner. Our responsibility is to express
in the group management report are detected
an opinion on the consolidated financial state-
with reasonable assurance. Knowledge of
ments and the group management report based
the business activities and the economic and
on our audit.
legal environment of the Group and expectations as to possible misstatements are taken into account in the determination of audit procedures. The effectiveness of the accounting-related internal control system and the evidence supporting the disclosures in the consolidated financial statements and the group management report are examined primarily on a test basis within the framework of the audit. The audit includes assessing the annual financial statements of the companies included in consolidation, the determination of the com panies to be included in consolidation, the accounting and consolidation principles used and significant estimates made by the Managing Directors of the managing corporate general partner, as well as evaluating the overall presentation of the consolidated financial statements and the group management report. We believe that our audit provides a reasonable basis for our opinion.
132
Boehringer Ingelheim A n n u a l R e p o r t 2 0 0 8
consolidated financial statements
With the following exception, our audit has not led to any reservations: Contrary to §314 paragraph 1 number 6 HGB compensation of the members and the former members of the board of managing directors and loans granted to these persons have not been disclosed. In our opinion, based on the findings of our audit, the consolidated financial statements with the exception mentioned comply with the legal requirements. The consolidated financial statements give a true and fair view of the net assets, financial position and results of operations of the Group in accordance with German principles of proper accounting. The group management report is consistent with consolidated financial statements that comply with the legal requirements and as a whole provides a suitable view of the Group‘s position and suitably presents the opportunities and risks of future development.
Frankfurt am Main, 12 February 2009 PricewaterhouseCoopers Aktiengesellschaft Wirtschaftsprüfungsgesellschaft (Philip Marshall)
(Klaus Höfer)
Wirtschaftsprüfer
Wirtschaftsprüfer
(German Certified
(German Certified
Public Accountant)
Public Accountant)
133
Auditor’s Report
If you have any queries or comments, please contact us.
Boehringer Ingelheim GmbH Binger Strasse 173 55216 Ingelheim Germany Telephone + 49 6132 77-0 Fax + 49 6132 72-3000 Contact CD Communications Dr Bernd Mann Telephone + 49 6132 77-92300 Fax + 49 6132 72-92300 E-mail
[email protected] Internet www.boehringer-ingelheim.com
Issued by Boehringer Ingelheim GmbH Design and layout Neufrankfurt Corporate Design GmbH, Offenbach am Main
[email protected] Photos Markus Hildebrand (page 3), Frank Ossenbrink (page 5), Jens Wunderlich (page 28, 34, 44, 70, 80), Chris Gomersall/RSPB Images (page 33), Peter Pulkowski (page 59), Eugenio Goulart (page 62), Boehringer Ingelheim (all others) Printed by Süddeutsche Verlagsgesellschaft, Ulm Copyright © Boehringer Ingelheim GmbH, 2009 All rights reserved. No part of this Annual Report 2008 may be reproduced or transmitted in any form or by any means, electronic or photocopy, without permission in writing from Boehringer Ingelheim GmbH.
Figures from third parties used in the annual report are based on data available at the time the financial statement was drawn up.
Contents 2 The shareholders’ perspective 4 Key aspects 2008 8 Corporate bodies
Corporate Responsibility The ethical principles that guide our company have created a culture of corporate responsibility and commitment. page 28
10 Group Management Report
Comparison of balance sheets/ financial data 1999—2008 (in millions of EUR)
30 Corporate Responsibility 30 Caring for our neighbours – “We care” 32 Environmental protection and occupational safety
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
400
344
322
302
242
267
233
554
547
539
1,992
2,217
2,467
2,840
2,767
2,712
2,900
2,886
2,972
3,177
849
1,135
1,008
1,689
2,462
2,756
3,396
3,043
1,638
1,739
3,241
3,696
3,797
4,831
5,471
5,735
6,529
6,483
5,157
5,455
944
1,021
1,014
971
1,000
1,085
1,229
1,280
1,387
1,561
1,870
1,938
2,314
2,360
2,537
2,477
3,013
3,137
2,912
3,496
459
477
1,002
1,055
1,134
1,333
1,247
945
1,015
1,312
Current assets
3,273
3,436
4,330
4,386
4,671
4,895
5,489
5,362
5,314
6,369
Total assets
6,514
7,132
8,127
9,217
10,142
10,630
12,018
11,845
10,471
11,824
Liabilities and equity (as of 31.12.)
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
Financial assets Fixed assets Inventories Accounts receivable (incl. deferred charges and deferred taxes)
Our own research and development continues to be the major driver of innovative, new medicines. page 44
30 Caring for patients – The viramune® Donation Programme
Intangible assets Tangible assets
Research & Development
Corporate Responsibility
Assets (as of 31.12.)
Cash and cash equivalents (incl. securities)
39 Our people Research & Development 46 Our R&D strategy 48 Our R&D sites 51 Non-clinical research and development 53 From test tube to bioreactor – A seamless path for biopharmaceuticals 53 Clinical development 56 2008 – The year of landmark trials 58 Bridge to academia
Human Pharmaceuticals
Shareholders’ capital
332
211
200
178
178
178
178
178
178
178
1,982
2,362
2,753
2,818
3,139
3,297
2,940
3,275
1,385
3,101
Net income
320
379
401
537
529
888
1,491
1,722
1,809
1,424
Total equity
2,634
2,952
3,354
3,533
3,846
4,363
4,609
5,175
3,372
4,703
0
0
1
203
188
193
216
188
167
190
Group equity
2,634
2,952
3,355
3,736
4,034
4,556
4,825
5,363
3,539
4,893
Provisions (incl. deferred taxes)
2,631
2,932
3,150
3,568
3,963
4,172
4,958
4,641
4,726
5,120
Reserves (incl. currency conversion difference)
We are committed to the goal of serving humankind through new drugs and therapies. page 62
Minority interests
60 Our business Human Pharmaceuticals 64 Highlights Branded Prescription Medicines* 67 Highlights Generic Prescription Medicines 68 Highlights Consumer Health Care
Liabilities (incl. deferred charges)
1,249
1,248
1,622
1,913
2,145
1,902
2,235
1,841
2,206
1,811
Total liabilities
3,880
4,180
4,772
5,481
6,108
6,074
7,193
6,482
6,932
6,931
Total liabilities and equity
6,514
7,132
8,127
9,217
10,142
10,630
12,018
11,845
10,471
11,824
Product Supply and Industrial Customer 74 Biopharmaceuticals
Product supply and Industrial Customer
76 Pharmaceuticals Production 78 Pharma Chemicals 79 Manufacturing excellence in our centre for global animal health vaccines Animal Health 81 Highlights Animal Health 84 Samples of the product portfolio 106 Consolidated Financial Statements 2008 108 Overview of the major consolidated companies 110 Consolidated balance sheet
Animal Health With innovative veterinary medicines that accommodate the needs of both man and animal, we are a reliable partner for animal owners and veterinarians. page 80
We produce drugs for our own Human Pharmaceuticals business in a globally coordinated production network. Furthermore we offer customised manufacturing services to our industrial customers. page 70
Summary of selected financial data
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
Net sales
5,086
6,188
6,694
7,580
7,382
8,157
9,535
10,574
10,952
11,595
Operating income
655
800
980
1,082
901
1,372
1,923
2,140
2,100
1,980
Operating income as % of net sales
12.9
12.9
14.6
14.3
12.2
16.8
20.2
20.2
19.2
17.1
Income after taxes
320
379
401
551
537
908
1,514
1,729
1,812
1,428
Income after taxes as % of net sales
6.3
6.1
6.0
7.3
7.3
11.1
15.9
16.4
16.5
12.3
Return on shareholders’ equity (in %)
13.8
14.4
13.6
16.0
15.0
23.1
34.2
37.4
35.0
42.2
Equity ratio (in %)
40.4
41.4
41.3
38.3
37.9
41.0
38.4
43.7
32.2
39.8
Cash flow
111 Consolidated profit and loss statement
737
791
1,117
1,049
1,059
1,430
2,069
2,317
2,392
1,997
Financial funds
1,055
1,094
1,645
2,645
3,516
4,015
4,585
3,934
2,581
2,932
Personnel costs
1,527
1,749
1,916
2,175
2,252
2,443
2,671
2,836
2,886
3,004
30.5
29.9
28.0
26.8
26.4
25.9
34,221 35,529
37,406
38,428
39,800
41,300
112 Cash flow statement
Personnel costs as % of net sales
113 Statement of changes in group equity
Average number of employees
114 Notes to the consolidated financial statements
Research and development costs*
132 Auditor’s Report
R&D as % of net sales
Flap Comparison of balance sheets / financial data 1999–2008
* The patient reports are authentic reports which refer to personal experience only. Please note that other patients may experience different treatment results. Individual treatment regimes have always to be discussed between patient and physician case by case.
28.3
28.6
28.7
27,325
27,980
31,843
826
968
1,019
1,304
1,176
1,232
1,360
1,574
1,900
2,109
16.2
15.6
15.2
17.2
15.9
15.1
14.3
14.9
17.3
18.2
Investments in tangible assets
377
497
548
634
516
427
532
596
654
665
Depreciation of tangible assets
256
288
305
340
354
377
439
419
432
453
* As��������������������������������������� of the year 2008, costs for phase IV clinical ���������������� trials are included in R&D costs, among other expenses. The 2007 figure was adjusted accordingly. please turn over
30.0 26,448
Financial Highlights Boehringer Ingelheim group of companies 2008
2007
change
11,595
10,952
6 %
Europe
33 %
33 %
Americas
48 %
50 %
Asia, Australasia, Africa
19 %
17 %
96 %
96 %
4 %
4 %
Research and development
2,109
1,900
11 %
Personnel costs
3,004
2,886
4 %
41,300
39,800
4 %
Operating income
1,980
2,100
- 6 %
Operating income as % of sales
17.1%
19.2 %
Amounts in millions of EUR, unless otherwise indicated
Net sales by region
by business
Human Pharmaceuticals
Boehringer Ingelheim
Animal Health
Annual Report 2008
Income after taxes
Annual Report 2008
www.boehringer-ingelheim.com
Average number of employees
1,428
1,812
12.3 %
16.5 %
4,703
3,372
42.2 %
35.0 %
1,997
2,392
-17 %
Investments in tangible assets
665
654
2 %
Depreciation of tangible assets
453
432
5 %
Income after taxes as % of sales Shareholders’ equity Return on shareholders’ equity Cash flow
-21 %
39 %
Value through Innovation Value through Innovation Top 5 products — Prescription Medicines
30234/03/09
Net sales 2008
nopq
Top 5 products — Consumer Health Care
in millions of EUR
change
Net sales 2008
in millions of EUR
change
spiriva®
2,070
+16 %
micardis®
1,219
+15 %
dulcolax®
134
+7 %
mucosolvan®
125
+7 %
flomax®/alna®
pharmaton®
1,075
+5 %
115
+21 %
mirapex®/sifrol®
752
+17 %
buscopan®
99
+24 %
combivent®
553
-15 %
zantac®
92
-17 %
