From Mind To Market - Boehringer Ingelheim

Value through Innovation
From Mind To Market

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Value through Innovation
Many of the world’s leading research-oriented
biopharmaceutical companies and top ranking
pharmaceutical organizations have discovered
the value of partnership with Boehringer
Ingelheim. We have proved time and time again
that we have the experience and the capability to
convert promising product ideas into commer cial
reality on a global scale. Throughout our history,
our expertise in development and manufacturing,
worldwide registration and marketing has achieved
significant patient benefit.
The Corporate Division Biopharmaceuticals at
Boehringer Ingelheim, is a process oriented
group. Together with its biotechnology units in
Vienna and Biberach it provides state-of-the-art
technology for developing and manufacturing
biopharmaceuticals. Bold, dynamic, and trustworthy,
our company provides the ideal conditions
for joint ventures to succeed. As a pioneer
in biopharmaceuticals, we can demonstrate
profound understanding of this exciting and
fast-moving field.
The Boehringer Ingelheim approach is reflected
in our mission statement: “Value through
Innovation”. This is more than simply sharing
financial risk. Our partners can rely on our
creativity to find cost-effective solutions to their
process development needs. They can accelerate
time to clinic and market, bring early return on
Prof. Dr. Dr. h.c. Rolf G. Werner
Boehringer Ingelheim GmbH
Corporate Division Biopharmaceuticals
investment and maximize patent life span, while
focusing on high quality and product safety. We
also recognize the importance of flexible, fully
integrated teamwork, and the need to tailor our
services and processes to the individual needs
of each company we partner. We can help at any
or every stage of the process, providing solutions
that may range from early development to largescale
manufacturing and worldwide marketing
agreements.
Our strategic partnerships are based on a team
approach. Working with our partners we can
provide the most efficient process development,
deliver goods at competitive prices, gain regulatory
approval worldwide and achieve global
market supply. As a fully integrated pharmaceutical
company we are also offering creative
solutions for joint product development through
clinical phases and worldwide marketing & sales
options. Being responsible for the strategic
orientation and the worldwide bio business at
Boehringer Ingelheim, I invite the biopharmaceutical
community to work with us and discover
that development and manufacturing don’t have
to be obstacles for new therapies on their way
“From Mind To Market.”

Company profile
The Boehringer Ingelheim group is one of the
world’s 20 leading pharmaceutical companies.
Headquartered in Ingelheim, Germany, it operates
globally with 137 affiliates in 47 countries
and nearly 38,500 employees. Since it was
founded in 1885, the family-owned company
has been committed to researching, developing,
manufacturing and marketing novel products of
high therapeutic value for human and veterinary
medicine.
We invest a large portion of our revenues in
research and development (R&D) and clinical
trials in the search for therapies that fulfil unmet
medical needs for humankind and animals. Our
basic research institutes meanwhile probe scientific
frontiers in search of answers to fundamental
questions about diseases and possible
treatments. Our key therapeutic areas are respiratory,
cardiovascular, metabolism, virology, central
nervous system (CNS), urology, immunology,
and oncology. In all these indication areas we
conduct R&D and clinical studies.
Boehringer Ingelheim: Our Group of Companies
The company’s R&D activities as well as the
production and distribution centres are spread
across the entire globe.
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Value through Innovation

Biotechnology pioneers
Boehringer Ingelheim began using bacteria for
the production of lactic acid in commercial
quan tities as early as 1895. This was the world’s
first successful use of microorganisms for large
scale product manufacture. By the mid-1930s,
the company had developed a process for large
scale product manufacture citric acid by fermentation
with fungi and deployed it for commercial
production.
Boehringer Ingelheim first extracted alkaloids
from plants in 1905. We were able to increase
production considerably from the 1960s onwards
by developing innovative techniques for culturing
and crop cultivation. This led to the commercial
introduction of products such as morphine
and codeine, and later, atropine, theobromine
and ergot alkaloids, all of which remain clinically
impor tant agents. Patents for biotechnical
manufacturing processes were issued, enabling
the replacement of natural processes.
In 1973, Boehringer Ingelheim began to work on
antimicrobial agents by chemically modifying
macrolide and beta lactam antibiotics to increase
potency, broaden spectrum of activity and overcome
resistance. Side-directed mutagenesis led
to new indolmycin derivatives. At the same time
we engaged in a screening programme to find
new lead compounds from streptomyces strains.
Our fermentation processes gave rise to several
new antibiotics, including amiclenomycin,
epidermin, gallidermin and gunacin.
The modern era of biotechnology, supported by
genetic engineering, began at the end of the
1970s with the manufacture of therapeutically
active proteins by genetic engineering. Again,
Boehringer Ingelheim took a pioneering role,
producing interferon beta, interferon omega and
Namalwa interferon from mammalian cell culture
and interferon alpha, interferon gamma and
manganese superoxide dismutase from microbial
sources. Boehringer Ingelheim’s growing reputation
in this emergent field led us into a number
of collaborations with well-known companies,
for example Amgen, Inc./Wyeth; Avidia, Inc.;
Genentech, Inc.; InterMune, Inc.; MedImmune,
Inc.; Merck KGaA; Schering AG; and others. We
have used recombinant DNA techniques since
1978, and to date have commercially manufactured
such clinically valuable proteins as rt-PA
(actilyse®), TNK-tPA (metalyse®), interferon
gamma (imukin®) and TNF alpha (beromun®)
for Boehringer Ingelheim’s markets.
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Biopharmaceutical organization
Boehringer Ingelheim RCV GmbH & Co KG
Vienna, Austria
Biopharmaceuticals: Microorganisms
Ben Venue Laboratories, Inc.
Bedford, Ohio, USA
Fill & Finish
Boehringer Ingelheim GmbH
Board of Managing Directors
Corporate Division Biopharmaceuticals
Ingelheim, Germany
Boehringer Ingelheim Pharma GmbH & Co. KG
Biberach, Germany
Biopharmaceuticals: Cell Culture, Fill & Finish
Boehringer Ingelheim Vetmedica, Inc.
St. Joseph, Missouri, USA
Veterinary Vaccines

The key to success
For any biopharmaceutical company, negotiating
the path from mind to market is a demanding
process. Very often, the burden of investment and
the complexity in developing and manufacturing
can be prohibitive, especially considering the risk
of failure at the clinical trial stage. Which is why,
companies are increasingly seeking to pool their
economic and intellectual resources by forming
strategic alliances.
We know every step of the way. We have the
resources. The scale of our operation, both in
terms of manufacturing capability and global
presence, befits our status as one of the world’s
leading 20 pharmaceutical companies. We have
the technology. Working in partnership with
Boehringer Ingelheim brings access to a state-ofthe-art
biopharmaceutical environment and a
wealth of accumulated knowledge and specialist
expertise. We have the expertise in process
and analytical sciences for the development of
economical processes with regulatory acceptance.
We have the track record. Many of the
world’s finest biotechnology companies have
achieved success in collaboration with Boehringer
Ingelheim and we can point to a long list
of innovative products already on the market or
in the pipeline due to our expertise.
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We know every step of the way
Genetic engineering
- Proprietary expression plasmids
- Efficient regulatory sequences
- High amplification
- Short cloning times
- Stable host vector system
There is no substitute for experience. At Boehringer
Ingelheim we have been directly involved with
commercial biotechnology for over one hundred
years. In every decade of our history we have
demonstrated an understanding of current technology,
the ability to recognize its new opportunities
and the corporate capacity to exploit them.
Very often we have lead the way developing new
techniques and manufacturing processes.
Cell-line development
- Suspension adapted host cell-line
- Adaptation to protein-free media
- Autocrine cell-lines
- Short generation times
- Cell banking (MCB/WCB)
Fermentation
- Media design
- Feeding strategy
- Process optimization
- Facilitated scale-up
- Large-scale cGMP
Downstream processing
- Refolding procedures
- Expanded bed chromatography
- Chromatography
- Ultrafiltration / diafiltration
- Microwave virus inactivation

Best fit for your strategic plan
All of the elements required for outsourcing bio-
pharmaceutical development and manufacture,
from high expression system to fill & finish,
can be found within the corporate capabilities
of Boehringer Ingelheim. We take a very flexible
approach in matching our strengths to our part-
ners’ needs. We can be your partner for all phases
of the development and production process, or
Formulation / fill & finish
- Protein-free formulations
- Aseptic filling
(vials, pre-filled syringes)
- Lyophilization
- Inhalative dosage forms
- Labelling and packaging
Quality control / assurance
- Structure elucidation
- Host cell proteins
- DNA contaminants
- Quality control assays
- cGMP compliance system
we have the ability to work with you at specific
stages, whether early or late phase. Whatever
your development and manufacturing objectives
are, Boehringer Ingelheim can provide precisely
what your strategic plan demands. Our skilled
staff with experience in process science and
cGMP is highly motivated to make your product
a success.
Worldwide registration
- Present in 47 nations
- Track record for more than
20 INDs/CTAs
- More than 10 BLAs/MAAs approved
- Contact to regulatory authorities
- Contribution to ICH guidelines
Option of marketing
- Global market research
- Worldwide distribution network
- Worldwide sales forces
- Local presence
- Reimport and pricing strategy
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We have the resources
In biopharmaceutical manufacture, Boehringer
Ingelheim is acknowledged and respected for
its expertise. Our commitment to excellence is
demonstrated by the high technical standard
of the development and manufacturing plants at
our disposal and, most important, by the quality
of our employees. They receive a high standard
of training and are committed to growing our
business. The production sites in Biberach
and Vienna doubled their biopharmaceutical
manufacturing capacity in the year 2003 and
2005 respectively, which reflects the growth
of our business.
Specialist expertise
From molecule to market, biopharmaceutical
manufacturing demands mastery of many
scientific disciplines and engineering skills.
At Boehringer Ingelheim you will find people
equipped to deal with every aspect of biotechnical
and biopharma processes, with a wealth
of accumulated experience and know-how to
draw on. Our expertise encompasses products
derived from mammalian cell cultures and from
microorganisms, as well as aseptic pharmaceutical
development and manufacture of formulated
bulk, labelling and individual packaging of
finished product.

Centers of Excellence
The global interests of Boehringer Ingelheim are
managed from our corporate headquarters in
Ingelheim, Germany, close to Frankfurt/Main Airport.
The Corporate Division Biopharmaceuticals,
which reports directly to the Board Member
Operations, is responsible for the worldwide
biobusiness. This Corporate Division develops
and maintains the global strategic concept for
our biopharmaceutical Centers of Excellence.
The activities of our state-of-the-art
biopharmaceutical centers:
Boehringer Ingelheim RCV GmbH & Co KG,
Vienna, produces therapeutically active proteins
from microorganisms and yeasts. Other areas
of production include microbial vaccines, plasmid
DNA for gene therapy, protein scaffolds and
antibody fragments. The site received the Frost
& Sullivan Technology Leadership Award and
the Customer Value Award 2004 for its provision
of superior contract manufacturing services to
customers across the globe.
Boehringer Ingelheim Pharma GmbH & Co.
KG, Biberach, Germany, has Europe’s largest
biopharmaceutical plant for the development
and manufacture of therapeutic proteins from
mammalian cell cultures. This site is also a major
fill & finish site for biopharmaceuticals. Several
of the world’s best-selling biotechnology products
are today produced at this site. The plant received
the “Industrial Excellence Award 2000 – Best
Factory” from the INSEAD Management Institute
in France and Germany’s WHU-Otto Beisheim
School of Management. Furthermore, it received,
together with Boehringer Ingelheim Austria, the
Frost & Sullivan 2004 Customer Value Award.
Ben Venue Laboratories, Inc., Bedford, Ohio,
USA, provides additional contract manufacturing
opportunities for aseptic filling and lyophilization
of biopharmaceuticals. Though its location
has obvious advantages for our US-based partners,
Ben Venue can supply markets around the
world.
Boehringer Ingelheim Vetmedica, Inc., St. Joseph,
Missouri, USA, manufactures and markets biotechnical
produced veterinary vaccines for the
Boehringer Ingelheim market. Technologies and
processes have been developed at Boehringer
Ingelheim Pharma GmbH & Co. KG, Germany
and are also applicable for manufacturing human
vaccines.
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We have the technology
As a partner in biopharmaceutical process science
and manufacture, we offer the world-class exper-
tise you would expect from a company which pioneered
the field. Also, the scale of operations
at our key biotechnical and pharmaceutical
plants, in terms of manpower and manufacturing
volume, allows us to meet ambitious production
requirements.
Continuous investment in our facilities allows
us to retain a strategic capacity for assignment
to contract manufacturing initiatives as well as
development programmes and attractive product
licensing arrangements. This provides flexible and
economic access to the manufacturing process
and helps accelerate entry to the market.
We offer all the security of an established company.
Our partners know they can rely on us to
respond to their needs by creating flexible and
integrated biopharmaceutical solutions, which
minimize their initial investment risk.

Microbial fermentation technology
Boehringer Ingelheim RCV GmbH & Co KG
pioneered the microbial fermentation and
purification of therapeutic proteins from E.coli
since 1982. Over the last decades the company’s
expertise and experience broadened to the development
and manufacture of gene therapeutics,
antibody fragments and protein scaffolds using
E.coli and yeast high expression technologies.
More than 500 skilled people of the Vienna plant
are dedicated to biopharmaceutical production
using microbial systems. The Process Science
Team has built high value Intellectual Property
for efficient and robust processes and is experienced
in process transfer and optimization. Business
process excellence guarantees continuously
innovative technologies improving process economy,
robustness, product safety and quality.
To secure an outstanding combination of scientific
know-how with state-of-the-art technology,
Boehringer Ingelheim Austria operates three
independent fermentation plants for E.coli and
yeast technologies: one medium-scale facility
with 300 litres and two large scale facilities with
6,000 litres. Both, batch and fed-batch fermentations
are performed. The new facilities allow
maximum flexibility and are designed for high
cell density processes requiring high oxygen
demand and high heat exchange. All plants are
operated by a validated process control system.
For downstream processing the purification plant
provides nine separate purification suites, varying
in size from 42 m2 to 280m2 where the processes
can be performed at room temperature
or 2 to 8 °C. Tanks up to 5,000 litres allow the
handling of large volumes during downstream
processing.
Furthermore, explosion-proof areas are in place
to allow steps requiring the use of organic solvents
or large scale high performance liquid
chromatography. Columns range up to 1.6 meter
diameter and techniques such as affinity chromatography,
size exclusion, hydrophobic interaction,
ion exchange, or reversed phase HPLC are
employed.
The plants are approved “multi-product” facilities
for the manufacture of products registered
with the Austrian Health Authorities, the EMEA,
MHLW and the FDA. Products are produced
under cGMP compliance for clinical trials and for
worldwide market supply.
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We have the technology
Setting the standard for pDNA production
Gene therapy and gene vaccines have been
moving out of the research laboratory and into
the clinic. These techniques promise to revolutionize
the treatment of a wide variety of
diseases. In order to meet the growing need for
pharmaceutical grade plasmid DNA (pDNA),
Boehringer Ingelheim RCV GmbH & Co KG has
developed a production process for pDNA utilizing
state-of-the-art technology. This process
employs high cell density fermentation, followed
by gentle cell lysis and a powerful downstream
process to produce pDNA of greater than 99 per
cent purity with very low levels of endotoxin and
genomic DNA. In addition, a host-vector system
is available which enables antibiotic-free selection
of small plasmid vectors devoid of antibiotic
resistance genes. By using this industrial pDNA
manufacturing technology no toxic organic solvents,
animal-derived enzymes or antibiotics are
necessary. To ensure the safety and functionality
of the product analytical methods have been
developed for both in-process control and final
product release that can detect all forms of DNA
and potential impurities.
The outstanding performance of this new process
allows upscaling of the fermentation and
purification process to large volumes under full
cGMP. The highly competitive process, which was
awarded with the Frost and Sullivan Technology
Leadership Award, is proprietary to Boehringer
Ingelheim and applied royalty-free for pDNA
production for our worldwide clients.

Mammalian cell culture technology
The 1 st multiproduct mammalian cell culture
facility at Boehringer Ingelheim Pharma GmbH
& Co. KG in Biberach was built in 1985 for the
commercial production of recombinant DNAderived
tissue plasminogen activator (rt-PA),
actilyse®. The story of the building is in itself an
example of our corporate will to succeed. The
entire project, from the empty site to the first
production of rt-PA, took only 18 months.
The pilot plant has a scale-up capacity of up to
2,000 litres fermentation volume and is used
for process development and for manufacture
of pre-clinical and clinical material. All relevant
disciplines for the establishment of a process are
integrated in our process science department,
facilitating technical transfer and making it as
economical as possible.
To ensure consistency in product quality during
up-scaling and clinical development, the fermentation
technology and the geometry of the
bioreactors are kept identical in the pilot and the
commercial multiproduct manufacturing plant.
Therapeutic proteins for advanced clinical trials
and for market supply are produced in the manufacturing
buildings under cGMP compliance.
Here the scale-up capacity ranges from 80 to
15,000 litres per fermentation train. With six
fermentation trains installed, the total volume
amounts to 90,000 litres downstream processing
is matched to the scale of fermentation.
Boehringer Ingelheim Pharma GmbH & Co. KG
in Biberach, Germany, expanded its cell culture
capacity with additional six fermenters of 15,000
litres volume each and corresponding downstream
capacity. The construction was completed
in 2003 and received regulatory approval in 2004.
The fill & finish operations were adjusted to the
enlarged manufacturing capabilities.
The total working volume of the mammalian cell
culture facility is now 180,000 litres.
At the plant there are today 1,600 skilled operators
promoting the biopharmaceutical business.
Specialists include biotechnologists, biochemists,
biologists, chemists, engineers, pharmacists and
others.
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We have the technology
Aseptic filling, lyophilization, labelling and packaging
With its two sites for aseptic processing, the
corporation has developed efficient methods
of aseptic filling, lyophilization, labelling
and packaging. Boehringer Ingelheim Pharma
GmbH & Co. KG in Germany has one of the
most modern and one of the largest facilities
for New Biological Entities (NBEs) in the world.
In addition to our recognition as a world leader
in this field, Ben Venue Laboratories facility
in Bedford, Ohio, USA, has received an uninter-
rupted series of development and manufacturing
contracts from 1967 up to date. Our experience
assures fast product and technology transfers,
enabling a smooth transition from the clinical
to the commercial phase.
Today, Boehringer Ingelheim has more than
twenty lyophilizers, with capacities ranging from
0.6 to 33 m2 of shelf area, making it one of the
largest facilities of its kind. All the lyophilizers are
computer controlled and optimized to enhance
drying rates and shorten cycles.
All plants are equipped and staffed to perform
full service under proven compliance.
Developmental capabilities include technology
platforms for therapeutic proteins, monoclonal
antibodies and nonviral vector systems for gene
therapy as vials, pre-filled syringes, and inhalative
devices.

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We have the expertise
Value and quality through innovation
Process sciences
Process sciences covers the Boehringer Ingelheim
biotechnical development and pharmaceutical
development chain. Moreover, it guarantees
Boehringer Ingelheim a constant supply of innovative
technologies improving process economy,
robustness, product safety and quality.
Drug substance development
The starting point of the biotechnical development
chain is the host cell expression system
development based on Boehringer Ingelheim’s
high expression vectors and high-throughput
clone selection to obtain robust high-producing
cells in shortest time. Based on the cultivation
of these cells, further activities in media design,
process and purification optimization lead to
an economic and robust basic manufacturing
process ready for scale-up.
With this integrated concept titres for monoclonal
antibodies of more than 4 g/litre have
been achieved. In the pilot facility optimization
of technical parameters and cGMP production
of clinical materials is conducted. For perfor-
mance of registration batches and production of
marketed material the processes are transferred
to the large-scale manufacturing facilities.
Drug product development
In the pharmaceutical development chain we
have the expertise and the technical possibilities
for the development and production of
clinical supplies of different dosage forms for
biopharma ceuticals.
For parenteral applications we can supply liquid
spray dried or lyophilized preparations in vials,
and ready-to-use syringes.
With two inhalation devices, respimat® and handihaler®,
Boehringer Ingelheim has pro prietary
devices for pulmonary administration
of biopharmaceuticals in liquid as well as in
solid preparations. The respimat® is a highly
innovative pocket size device, which produces
a slow-moving cloud and achieves high lung
deposition. The powder inhaler handihaler®,
likewise pocket size, can deliver up to 50 mg of

powder. This system is suitable in particular for
high doses or drug substances not sufficiently
stable in solution.
The technology portfolio of Boehringer Ingelheim
biopharmaceuticals also contains non-viral
gene vectors for in vivo application of genes. We
develop special DNA cationic lipid complexes
and DNA entrapped in resomer® particles. The
particle size and composition are optimized
to transfer genes efficiently without toxic sideeffects.
Analytical development and
quality control
Protein analytical chemistry is constantly evolving.
Improvements are continuously being made
with respect to the sensitivity and selectivity of
analytical assays. The most advanced analytical
tools are applied to ensure the concept of “well
characterized biopharmaceuticals”. The selection
of appropriate methods at each stage of development,
from early development to registration, is
essential for success.
Using protein analytical chemistry, we character-
ize the primary structure of complex proteins
and monitor the potential impact of process
optimization and scale-up on the product quality
in accordance with worldwide regulatory guide-
lines.
Thereby we ensure the equivalence of biopharma-
ceuticals, thus reducing the need for lengthy
and expensive clinical investigations.
EMEA/FDA approval and more
The multiproduct manufacturing facilities at
Biberach and Vienna are inspected by the Euro-
pean Medicines Evaluation Agency (EMEA),
the FDA, and Health Canada. They hold the license
for a number of products. All plants meet the
requirements of the World Health Organization
(WHO) and the Pharmaceutical Inspection
Convention (PIC). Additionally, the facilities
are subject to regular scrutiny by the health
authorities, consultants and quality assurance
units of our partners. The company’s policy is
to maintain a high level of compliance.
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We have the track record
Ongoing cooperations
Australia:
Sydney
Austria:
Vienna
Belgium:
Ghent
Germany:
Aachen
Berlin
Bielefeld
Cologne
Darmstadt
Dortmund
Düsseldorf
Erlangen
Freiburg
Giessen
Greifswald
Halle
Heidelberg
Hilden
Laupheim
Marburg
Munich
Regensburg
Stuttgart
Tübingen
India:
Bangalore
Ireland:
Galway
Japan:
Katata
Kyoto
Osaka
Tokyo
Malaysia:
Nilai
Sweden:
Stockholm
Switzerland:
Zürich
Taiwan:
Taipei
Thailand:
Chiang Mai
We have the capacity
Boehringer Ingelheim has established global
strategic alliances with dedicated process
development and manufacturing companies.
This concept ensures high flexibility, short
timelines and available capacity resulting in
a great benefit for our customers. Boehringer
Ingelheim provides commercial scale production
and early market supply with Marketing and Sales
(M & S) option through Boehringer Ingelheim’s
global M & S organisation.
UK:
Glasgow
Oxford
USA:
Boston, MA
Bothell, WA
Brisbane, CA
Cambridge, MA
Emeryville, CA
Framingham, MA
Gaithersburg, MD
Los Angeles, CA
Minneapolis, MN
New Jersey
New York, NY
Palo Alto, CA
Philadelphia, PA
Princeton, NY
Richmond, CA
Salt Lake City, UT
San Diego, CA
San Francisco, CA
Seattle, WA
Syracuse, NY
Worldwide presence
Boehringer Ingelheim has established its reputation
with the successful market introduction of
13 DNA-derived biopharmaceutical products.
Four of these products are among the top 20 of
the worldwide selling list. As our new products
show, we are continuing to move ahead, advancing
with the benefit of our own research, through
collaboration with research-oriented companies
and our commercial partners, and working with
leading academic networks.

Boehringer Ingelheim around the globe
Europe
Austria
Belarus
Belgium
Bosnia and
Herzegovina
Bulgaria
Croatia
Cyprus
Czech Republic
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Ireland
Italy
Latvia
Lithuania
Macedonia
Malta
Montenegro
Norway
Poland
Portugal
Romania
Russia
Serbia
Slovakia
Slovenia
Spain
Sweden
Switzerland
The Netherlands
Ukraine
United Kingdom
Americas
Argentina
Brazil
Canada
Chile
Colombia
Ecuador
Mexico
Peru
Uruguay
USA
Venezuela
Africa, Asia,
Australasia
Australia
Bahrain
China
Egypt
Ethiopia
Hong Kong
India
Indonesia
Iran
Iraq
Japan
Jordan
Kazakhstan
Kenya
Kuwait
Lebanon
Libya
Malawi
Malaysia
Mauritius
New Zealand
Nigeria
Oman
Pakistan
Palestine
Qatar
Saudi Arabia
Seychelles
Singapore
Somalia
South Africa
South Korea
Sudan
Syria
Taiwan
Tanzania
Thailand
The Philippines
Turkey
Uganda
United Arab
Emirates
Vietnam
Yemen
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We have the track record
Many organizations have achieved success by
partnering with Boehringer Ingelheim. The list
ranges from small research-based operations to
large multinational pharmaceutical companies.
Our most well-known biotechnology alliance is
perhaps with Genentech, Inc., San Francisco,
with which we have worked closely since 1983.
Together we developed the recombinant DNAderived
tissue plasminogen activator (rt-PA),
a thrombolytic agent used in the treatment of
myocardial infarction, pulmonary embolism and
stroke. rt-PA was marketed in North America
by Genentech as activase®, and by Boehringer
Ingelheim in over 50 countries under the trade
name actilyse®. It is the most successful biopharmaceutical
manufactured and marketed by
Boehringer Ingelheim. The two companies have
worked together on the next generation of tissue
plasminogen activator which as TNKase® in the
USA, and as metalyse® in Europe has helped
an increasing number of AMI (Acute Myocardial
Infarction) and stroke patients since 2001.
Other products jointly developed in collaboration
with Genentech are imukin® (interferon gamma),
which is approved for chronic granulomatosis,
and tumor necrosis factor (TNF) alpha, for the
treatment of soft tissue sarcoma, under the
brand name beromun®.
In order to maintain and improve our competitive
edge in a constantly evolving field, we maintain
strong links with a number of universities
and industrial partners in the area of new technologies,
such as expression systems, optimized
host cells, media and process optimization,
expanded bed absorption, affinity chromatography,
virus inactivation, on-line analysis, refolding
and new application forms.
Own biopharmaceuticals brought to market:
Generic name Brand name Therapeutic area
Tissue plasminogen actilyse® Myocardial infarction,
activator (rt-PA) pulmonary embolism,
stroke
Second generation metalyse® Myocardial infarction
tissue plasminogen
activator (TNK-tPA)
Interferon gamma imukin® Chronic granulomatosis
Tumor necrosis beromun® Soft tissue sarcoma
factor alpha
For customers Boehringer Ingelheim so far introduced
9 DNA-derived biopharmaceutical products
to the market.

R &D at Boehringer Ingelheim
As a research-driven pharmaceutical company,
Boehringer Ingelheim is committed to the goal
of discovering and developing products which
represent high therapeutic value for patients,
physicians and health care providers.
R&D Centers are located in Biberach, Ger-
many, Ridgefield, USA; Vienna, Austria; Laval,
Canada; and Kawanishi, Japan. Our R&D activities
embrace the therapeutic areas of respiratory,
cardiovascular, metabolism, virology, central nervous
system, urology, immunology and oncology.
Boehringer Ingelheim’s R&D focuses on identifying
and developing new chemical entities and
new biological entities, such as therapeutic proteins
or gene therapies. Projects from the latter
category draw particular advantage from our
in-house biopharmaceutical manufacturing
expertise.
All R&D in Boehringer Ingelheim’s therapeutic
areas are supported by in-licensing for early and
late stage innovative pharmaceutical and biopharmaceutical
products.
In-licensing projects are evaluated in a short time
period and licensing deals are tailored according
to a partner’s individual needs. Together with
our capabilities in process science we can offer
attractive solutions for our licensors.
Therefore, for biopharmaceuticals, an integrated
approach ranging from product development to
marketing is highly attractive for the licensor.
In collaboration with our strategic partners and
from our own research efforts, we currently have
a number of promising compounds at various
stages of development.
Our areas of in-licensing interest:
- Respiratory - CNS
- Cardiovascular - Urology
- Metabolism - Immunology
- Virology - Oncology
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Work with us
Companies choose contract development and
manufacturing because it offers an attractive
solution to bring a biopharmaceutical to market
as efficiently as possible, without prohibitive
financial risk. Companies choose to work with
us in particular, because our experience and
resources guarantee competitive manufacturing
processes and timely market supply. They find that
we are not only innovative in the technical sense,
but that our team brings a creative approach to
our partnerships.
The team approach
Inter-company teams run all our partnership
projects. These experts agree on the timelines
and interim objectives required in developing a
manufacturing process with optimum efficiency,
safety and cost-effectiveness. Designated project
managers from each side coordinate the process,
meeting regularly with team members and, when
not meeting in person, keeping in touch by telephone
and videoconferences. A project group
will typically contain senior scientists from process
science, fermentation and downstream
processing, fill & finish, quality control and
quality assurance.
Naturally, everyone assigned to a project team
at Boehringer Ingelheim has extensive experience
in biopharmaceutical development, manufacturing,
quality and regulatory issues. As a matter of
company policy, our employees follow an intensive
cGMP education programme. In addition,
where new skills and techniques are involved,
we provide project-specific training.

Finding the best-fit strategy for your product
Projects, where the expectation of success in
clinical trials is high, can be developed with a
time to market strategy. In this approach, key
phases are conducted in parallel, allowing
the shortest possible timeline and the earliest
possible return on investment.
For highly innovative projects, carrying a certain
development risk during pre-clinical and clinical
evaluation, we are open to a step-by-step
approach. However, this strategy necessarily
requires a longer development phase for the
manufacturing process and consequently delays
entry to the market and return on investment.
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Time to market
Tailor-made service concept for our customer
Product development 1 2 3 4
Cell biology
Feasibility study
Small scale
Pilot scale
Commercial scale
Pre-clinic
Toxicology
Proof of concept I/IIa
Phase IIb
Phase III
Registration package
Registration
Market supply

5 6 7 8 9 10 11 year
The time to market approach provides the fasttrack
process development to commercial scale
and early market supply and thus an early return
on investment. However, this may carry a high
financial risk being dependent upon successful
clinical results.
The modular composition of our development
programmes means that a partnership can be
initiated at any phase in the process and tailored
to individual requirements.
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Contact us
This brochure is an introduction to the
cooperative services we offer
in biotechnical and biopharmaceutical manufacturing.
For more information please contact:
Prof. Dr. Dr. h.c. Rolf G. Werner
Boehringer Ingelheim GmbH
Corporate Division Biopharmaceuticals
Binger Strasse 173
D-55216 Ingelheim am Rhein
Germany
e-mail: biopharma@bc.boehringer-ingelheim.com
internet: www.boehringer-ingelheim.com/biopharm
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Boehringer Ingelheim GmbH
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Copyright
© Boehringer Ingelheim GmbH, 2006
All rights reserved. No part of this brochure may be
reproduced or transmitted in any form or by any means, electronic or
photocopy, without permission in writing from
Boehringer Ingelheim GmbH.
27936/02/09
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