Biomfg Report

8th Annual
Report and Survey of

Biopharmaceutical Manufacturing
Capacity and Production
A Study of Biotherapeutic Developers and Contract
Manufacturing Organizations
April 2011
associates, inc.
BioPlan Associates, Inc.

2275 Research Blvd., Suite 500
Rockville, MD 20850 USA
301.921.5979
www.bioplanassociates.com
Copyright ©2011 by BioPlan Associates, Inc.

All rights reserved. Unauthorized reproduction prohibited.
8th Annual Report and Survey of Biopharmaceutical
Manufacturing Capacity and Production
April 2011

2275 Research Blvd, Suite 500
Rockville MD 20850
301-921-5979
Copyright © 2011 by BioPlan Associates, Inc.
All rights reserved, including the right of reproduction in whole or in part

in any form. No part of this publication may be reproduced, stored in a
retrieval system, or transmitted in any form or by any means, electronic,
mechanical, photocopying, recording or otherwise, without the written
permission of the publisher.
For information on special discounts or permissions contact

BioPlan Associates, Inc. at 301-921-5979, or info@bioplanassociates.com
Managing Editor: Eric S. Langer

Project Director: Krista Meisel
Layout and Cover Design: ES Design
ISBN 978-1-934106-21-1
FRONT COVER PHOTOS (L.to R.):

Magnetic Mixer Single-use Mixing System. Courtesy of ATMI LifeSciences.
Simple to Complex Single-use Assemblies. Courtesy of Cole-Parmer’s BioConnect® service.
Xcellerex Flex Factory Installation. Courtesy of Xcellerex.
Silicone Tubing. Courtesy of Dow Corning Corporation.
ACKNOWLEDGMENT
We wish to acknowledge the contributions of our authors and Subject Matter Experts.
Without their thorough analysis of the data this project would not have been possible:
❚ E. Faye Coggins, Founder and Principal of BioTraction Associates, LLC
❚ Thomas E. Colonna PhD/JD Assoc Dir BioScience RA, Johns Hopkins
University
❚ Nicholas Folger, President, Jobs Board, Life Science Postgrads, Bio
Careers, Inc
❚ Alfred C. Dadson Jr., Sr. Director, Manufacturing Operations, XOMA LLC
❚ Geoff Hodge, VP, FlexFactory® Contract Manufacturing Services,
Xcellerex, Inc.
❚ Rick Johnston, PhD, Principal, Bioproduction Group, Inc.
❚ Storm Lefelar, Consultant, Storm Biotechnology
❚ Wolfgang A.W. Noe, Ph.D., Senior Consultant of BioProcess Technology
Consultants
❚ Ronald A. Rader, President, Biotechnology Information Institute
❚ Rowena L. Roberts, PhD, Founder and Principal of BioTraction
Associates, LLC
❚ James Dean Vogel, P.E., President, BioProcess Institute
❚ Abdul Wajid, PhD, Sr. Director, Process Sciences, XOMA LLC
❚ Scott Wheelwright, President, Strategic Manufacturing Worldwide, Inc.
We would also like to recognize our sponsoring organizations, and our media
sponsor. Their efforts in assuring the cooperation and participation in the survey
of their respective memberships helped guarantee the large group of survey
participants to ensure data accuracy.
Our Sponsoring Institutions, all of whom contributed their time and effort to ensure the
broad, international coverage of this project, include:
❚ AusBiotech (Malvern, Victoria, Australia)
❚ ASME-BPE
❚ ABO China (Beijing, China)
❚ Beijing Pharma and Biotech Center (Beijing, China)
❚ BioProcessUK (London, United Kingdom)
❚ BioPharm Insight (Norwood, MA)
❚ BioForward (Madison, WI)
❚ BPSA-SOCMA (Washington, DC)
❚ Massachusetts Biotechnology Council (Cambridge, MA)
©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED iii
Report and Survey of Biopharmaceutical Manufacturing Capacity and Production
To ensure global coverage for this project, this year we invited major Media
Sponsors to support our outreach to biopharmaceutical decision-makers. This year,
our media sponsors helped ensure broad and representative coverage of industry
participation:
❚ BioProcess International, (Westborough, MA)
❚ Biopharm International (Iselin NJ)
❚ BioProcessing Journal (Winthrop, MA)
❚ Contract Pharma, (Ramsey, NJ )
❚ CanBiotech (Mississauga, Canada)
❚ Genetic Engineering News (New Rochelle, NY
❚ Life Science Leader (Sewickley, PA)
❚ Pharmaceutical Manufacturing Journal (Itasca, IL)
❚ Pharmaceutical Technology (Iselin, NJ)
The early participation of our authors and sponsors in evaluating the areas and
trends to be surveyed this year ensured the project was designed to cover the most
relevant issues in biopharmaceutical manufacturing today. Their support was, again
this year, critical to the success of the project.
Eric S. Langer
Editor
iv WWW.BIOPLANASSOCIATES.COM
A B O U T B I O P L A N A S S O C I AT E S , I N C .
BioPlan Associates, Inc. is a biotechnology and life sciences market
analysis, research, and publishing organization. We have managed
biotechnology, biopharmaceutical, diagnostic, and life sciences
research projects for companies of all sizes since 1989. Our extensive
market analysis, research and management project experience covers
biotechnology and biopharmaceutical manufacturing, vaccine and
therapeutic development, contract research services, diagnostics,
devices, biotechnology supply, physician office labs and hospital
laboratory environments.
We prepare custom studies, and provide public information our clients
require to make informed strategic decisions, define objectives, and
identify customer needs. With market information, our clients are better
able to make informed, market-based decisions because they understand
the trends and needs in high technology industries.
2275 Research Blvd., Suite 500
Rockville, MD 20850 USA
Tel: 301-921-5979
©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED v
E D I TO R :
Eric S. Langer, MS, President, BioPlan Associates, Inc.
Mr. Langer is President and Managing Partner and President of BioPlan Associates, Inc. a
biotechnology and life sciences consulting company that has been providing management
and market strategy services, and technology analysis to biopharmaceutical and healthcare
organizations since 1989. He has over 20 years experience in biotechnology and life
sciences management and market assessment. He is an experienced medical and
biotechnology industry practitioner, strategist, researcher, and science writer. He has held
senior management and marketing positions at biopharmaceutical supply companies. He
teaches Biotechnology Marketing, Marketing Management, Services Marketing, Advertising
Strategy, and Bioscience Communication at Johns Hopkins University, American University,
and lectures extensively on pricing and channel management topics. Mr. Langer has a
degree in Chemistry and Masters in International Business. He has written and consulted
extensively for companies involved in: large scale biopharmaceutical manufacturing, global
biotechnology in China, Asia, and the Middle East; he has expertise in cell culture markets,
media, sera, tissue engineering, stem cells, diagnostic products, blood products, genetics,
DNA/PCR purification, blood components, and many other areas.
ABOUT THE AUTHORS (ALPHABETICAL)
E. Faye Coggins, Founder and Principal of BioTraction Associates,

LLC
Ms. Coggins has over 30 years experience in life science companies at executive level
positions in both the diagnostics and biotechnology markets. She has extensive experience
in management, business, marketing, sales, new product development and organizational
coaching and development in life sciences companies. Ms. Coggins has held positions as
VP Marketing for Fisher Biosciences LSR Division, Executive Director of Marketing, North
America, QIAGEN Inc., Vice President of Marketing and Sales at Cylex, Inc. a venture
based company focused on immune cell function; and Vice President of Worldwide
Marketing at Life Technologies, Inc. In addition, Ms. Coggins has held several senior level
business, marketing and sales positions, the last being Marketing Director of New Product
Development at DuPont in its $1 Billion Medical Products Division (now Siemens). Ms.
Coggins received a B.S. in Medical Technology from East Carolina University and holds
a MT (ASCP) certification. She has received executive training in Marketing Management
from Columbia University and Strategic Planning from the Wharton School of Business.
In addition Ms. Coggins served as President Elect, President, and Past President of the
Clinical Laboratory Managers Association (CLMA) from 1995-2001.
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AUTHORS
Thomas E. Colonna PhD/JD Associate Director BioScience

Regulatory Affairs Program, Johns Hopkins University, &
GM Biotech-Consultant LLC
Dr. Colonna has a broad educational background with a BS (Microbiology) from the
University of Sciences in Philadelphia (formerly the Philadelphia College of Pharmacy
and Science), a PhD (Molecular Biology) from the Johns Hopkins University, and a JD
from the Georgetown University Law Center. In addition to his consulting practice, Dr.
Colonna is the Associate Director of the Bioscience Regulatory Affairs program at the Johns
Hopkins University. He has published extensively in several areas including authoring and
editing two books published by the Food and Drug Law Institute: Promotion of Biomedical
Products: Regulatory Considerations and Biomedical Software Regulation. Dr. Colonna
is also the founder and director of the 501(c)(3) non-profit Regulatory Affairs Institute.
TColonna@Biotech-Consultant.com
Alfred C Dadson Jr, Sr Director, Manufacturing Operations,

XOMA LLC
Al has over 29 years of biotechnology experience and has been with XOMA for over 9
years and is currently Sr Director, Manufacturing Operations of antibodies and proteins
through API production. He has over 26 years of biotechnology experience with 20 years at
Bayer Healthcare where he played a key role in the development of several biotechnology
products including Kogenate®. While at Bayer Healthcare, he held positions from R&D to
technology development. At Bayer Healthcare, Al was a Sr Staff Scientist/Manager of the
Process Sciences Clinical Fermentation group.
Nicholas Folger, President, Jobs Board for Life Science

Postgraduates Bio Careers, Inc
Nick Folger founded Bio Careers in 2006 driven by the need for a multi-university jobs
board and career services for the life science community. www.biocareers.com was
developed to expand career options for life science postgraduates and MDs and to
connect this growing number of professionals with hiring employers. Folger also founded
Edge Sports Corporation in 2002. Edge Sports was a mass customization and innovation
company in the team sports uniform market. Prior to Edge Sports, Folger led the Dockers
Khakis U.S. marketing team and the Dockers Europe sales and marketing team for the
highly successful launch of the Dockers brand into Europe. The business grew from $5MM
to $180MM in wholesale sales, and from 30 to over 3,200 points of sale during his tenure.
Before joining Levi Strauss & Co., Folger attended Stanford Graduate School of Business,
where he focused on marketing and entrepreneurship.
Folger also holds a B.A. degree, with honors, from Harvard University.
©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED vii
Geoff Hodge, Vice President, FlexFactory® Contract Manufacturing

Services, Xcellerex
Geoffrey Hodge is Vice President, FlexFactory® Contract Manufacturing Services at
Xcellerex, an equipment vendor and contract manufacturing and development company
based in Marlborough, Massachusetts. He is responsible for contract manufacturing
services and validation within Xcellerex’s 3 GMP FlexFactory® manufacturing suites and
support of FlexFactory® TransPlant customers in the field. Prior to joining Xcellerex, Mr.
Hodge was Associate Director of Process Development at Millennium Pharmaceuticals,
Cambridge, MA, with responsibility for the process development and clinical manufacturing
of Millenniumís biologics pipeline. In this role he pioneered the use of disposable
manufacturing systems for the production of monoclonal antibodies and helped to develop
a novel manufacturing platform and many of the high-throughput process development
technologies subsequently licensed to Xcellerex. Mr. Hodge has also held positions in
commercial manufacturing as Manufacturing Section Head at Genetics Institute (now
Wyeth BioPharma), Andover, Massachusetts, and various management positions in
process development, clinical manufacturing, manufacturing and validation at Alpha-Beta
Technology, Worcester, Massachusetts. Mr. Hodge received his B.A. in Biology from Colgate
University, and his M.S. in Biotechnology from Worcester Polytechnic Institute.
Wolf Noe, Sr. Consultant with Bioprocess Technology Consultants

Wolfgang A.W. Noe, Ph.D., Senior Consultant of BioProcess Technology Consultants, has
~ 30 years of experience in the biopharmaceutical industry. Prior to joining BPTC, Dr. Noe
was Vice President of Strategic Alliances & Technical Development at BiogenIDEC. Before
that, Dr. Noe was overseeing Bioprocess Development at BiogenIDEC. Before joining Idec
([later Biogen-Idec) in 2001, Dr. Noe was with Boehringer-Ingelheim in several assignments
(including head of manufacturing alliances, head of clinical manufacturing, head of
cell culture development). Dr. Noe holds a Ph.D. in Biochemistry from the University of
Tuebingen and completed a post-doctoral fellowship at GBF in Germany and an Associate
Professorship at the University of Freiburg/Germany
Ronald A. Rader, President, Biotechnology Information Institute

Mr. Ronald A. Rader has been President of his own publishing/consulting company, the
Biotechnology Information Institute, since late 1990. Mr. Rader has a B.S. (Microbiology),
M.L.S. (Library/Info. Sci.), and 30 years experience as a biotechnology and pharmaceutical
information specialist, author, publisher and consultant. He is a world-class expert in
biotechnology and pharmaceutical information, competitive intelligence, technology
and market assessments, and information resources development; and concerning
biopharmaceutical products and the industry Mr. Rader is author and publisher of
BIOPHARMA: Biopharmaceutical Products in the U.S. and European Markets, reference
concerning biopharmaceuticals, and for 15 years (1987-2003), he was author and publisher
of the Antiviral Agents Bulletin. He also authored Biopharmaceutical Expression Systems
and Genetic Engineering Technologies: Current and Future Manufacturing Platforms and a
variety of market and technology assessments for BioPlan Associates.
viii WWW.BIOPLANASSOCIATES.COM
AUTHORS
Rowena L. Roberts, PhD, Founder and Principal of BioTraction

Associates, LLC
Dr. Roberts has over 25 years of management experience in the life science research,
medical device, and food diagnostics markets. Her experience includes marketing,
product management, new product development, strategic planning, R&D management,
basic and applied research, and market research. Dr. Roberts has held positions as
Director of Marketing and Sales at BioInformatics, a market research consultancy,
Senior Director of Marketing and R&D at KPL, Inc, a company specialized in antibodies
and protein detection, Business Director at IGEN (now part of Roche Diagnostics) with
responsibility for development of a food pathogen detection business, Product Line
Business and Marketing Manager at Life Technologies, and Commercial Development
Manager for biomedical products for the National Medical Care subsidiary (now Fresenius
Medical Care) of W. R. Grace. Dr. Roberts holds a Ph.D. from the University of Texas and
an M.B.A. from the University of Maryland.
Abdul Wajid, Ph.D., Sr. Director, Process Sciences XOMA (US) LLC
(Berkeley, CA)
Dr Wajid has been working for XOMA for the last eight years directing Fermentation
development, Media development and Purification development processes with additional
responsibility of scale-up and process transfer to Manufacturing. Wajid, has over 20
years experience in all facets of biologics development including clinical and commercial
manufacturing. Prior to joining XOMA, he worked at Aventis Pasteur (Toronto, ON) as
an Associate Director, Bacterial Manufacturing Operation, responsible for scale-up and
manufacturing of Component Pertussis subunit vaccine.
Storm Lefelar, Consultant, Storm Biotechnology

Mr. Lefelar working with The BioProcess Institute, and runs Storm Biotechnology (http://
www.stormbiotechnology.com). Storm is a 20 year veteran of the Bio-Pharmaceutical
Industry. Services his team provides include cGMP Manufacturing support and guidance,
hands-on start-up support, FDA/EMEA compliance expertise, all facets of facilities
support, risk assessments and remediation advice. Prior to starting Storm Biotechnology
in 2008, Storm served as Vice President of Operations for Goodwin Biotechnology; leading
the Operations team through Goodwin’s two most successful years in their 17 year history.
Storm was also manufacturing manager for DSM biologics and did a complete upgrade of
mechanical and GMP compliance systems to meet commercial manufacturing standards
at their Montréal facility. While working for seven years at Wyeth Biopharma, he was a
member of the tech transfer team that provided transfer of the Enbrel process from Amgen
Rhode Island to Wyeth Grange Castle. ImClone Systems was where Storm got his start in
biotechnology. Storm earned his B.S. from Trinity College.
©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED ix
James Dean Vogel, P.E., Founder and Director, The BioProcess

Institute
Mr. Vogel has more than 27 years of experience in the biopharmaceutical, food and
cosmetic industries. He has worked as a Director, Project Manager, and Engineer
(Plant Support, PD, Project and Automation), with Amgen, GlaxoSmithKline, ImClone,
Sanofi-Pasteur, Lipton and Avon. The BioProcess Institute provides operational
consulting to BioPharmaceutical companies and vendors. The Institute offers a
portfolio of standard and customized testing and analysis services including fitness
for use, proof of concept and failure mode effects analysis (FMEA) for single-use and
multi-use manufacturing components. He was the lead designer for a $700 million
large scale BioPharmaceutical plant, and directed numerous facility renovations
including upgrades to the buildings, process equipment, utilities, and laboratories. Mr.
Vogel is an Adjunct Professor at Stevens Institute of Technology, leader of programs
at the University of Rhode Island, a member of the American Society of Mechanical
Engineers (ASME) BioProcess Equipment (BPE) Standard Committee, Chairman of
the ASME BPE Seals Subcommittee, a member of the ISPE Disposables Community
of Practice Steering Committee, and the PDA. He has a Masters of Engineering
in Chemical Engineering from Manhattan College and a Bachelors of Science in
BioChemical Engineering from Rutgers University. www.bioprocessinstitute.com
Scott M. Wheelwright, Ph.D., Founder and Principal, Strategic

Manufacturing Worldwide, Inc.
Dr. Wheelwright has over twenty years experience in bringing novel products to
market, including new drug applications (BLAs and NDAs) in the US and Japan,
numerous investigational applications (INDs) and commercial product launches. Dr.
Wheelwrightís work experience encompasses pharmaceutical firms and both large
and small biotech companies, including Abbott, Chiron, and Scios. Dr. Wheelwright
received his Ph.D. in chemical engineering from the University of California at Berkeley
and continued post-doctoral studies at the Max Planck Institute for Biophysics
in Frankfurt, Germany. He is the author of a book on protein purification and has
published numerous articles on manufacturing and process development. Dr.
Wheelwrightís focus is on long-term strategic and near-term planning for development
(CMC issues including process development, analytical testing and characterization),
manufacturing and facilities. Dr. Wheelwright recently opened an office in Shanghai to
assist clients in Asia with outsourcing and cGMP compliance.
x WWW.BIOPLANASSOCIATES.COM
8th Annual Report and Survey of
Biopharmaceutical Manufacturing
Capacity and Production • April 2011
CONTENTS
Overview ........................................................................... xxix
Market Trends ........................................................................................xxix
Market Potential ...................................................................................xxxiv
Methodology..................................................................... xxxvii
CHAPTER 1:Introduction and Discussion..........................................1

Introduction ..........................................................................................................1
The Biopharmaceutical Pipeline ...............................................................3
1-1 U.S. and World Biopharmaceutical and Recombinant
Protein/Mab Markets ......................................................................................8
Biosimilars and Bio-betters ......................................................................10
BRIC Country Growth ..............................................................................10
Expression Systems Today ......................................................................13
Biosimilars Are Expanding the Biopharmaceutical Industry .....................16
1-2 Expression Systems in Biopharmaceutical Manufacturing.....................19
1-3 Continuing Need for Production Improvements and
Cost Containment ........................................................................................20
Biotherapeutic Developers .......................................................................21
CMOs .......................................................................................................21
Industry Suppliers ....................................................................................21
Government .............................................................................................22
©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED xi
CHAPTER 2: Demographics ....................................................... 23

Respondents’ Area of Involvement ..........................................................23
Respondents’ Titles ..................................................................................26
Respondents’ Facility Locations...............................................................27
Respondents’ Areas of Biopharmaceutical Manufacturing Operations ....29
Respondents’ Production Operations, Phase of Development ................30
Employees at Facility ...............................................................................31
Batches Run at Facility per Year ..............................................................32
CHAPTER 3:Emerging Issues in Biopharmaceutical Manufacturing ........ 35

3-1 Budget Issues in 2011 ................................................................................35
Budget Change Comparisons .................................................................38
3-2 Operational Changes in 2011 ....................................................................40
Operational Changes: 2011 vs 2010 ........................................................43
Operational Changes: Biotherapeutic Developers vs CMOs ...................44
Operational Changes: US vs Western Europe ........................................46
3-3 New Product Development Opportunities in 2011 ...................................49
New Product Development Focus, 2011 vs 2010 ....................................54
New Product Development Areas: Biotherapeutic
Developers vs CMO’s .........................................................................56
New Product Development Areas: Biotherapeutic US vs
Western Europe and ROW .................................................................58
3-4 Factors in Biomanufacturing Creating Improvements ............................60
Factors Improving Biomanufacturing Performance, 2011 vs 2010 ..........62
Factors Improving Biomanufacturing Performance, Biotherapeutic
Developers vs CMOs .........................................................................66
Factors Improving Biomanufacturing Performance, US vs
Western Europe, vs ROW ..................................................................68
3-5 Cost-Cutting Actions & Development Timelines.......................................70
Cost-Cutting Changes: Specific to Outsourcing.......................................72
Activities Implemented to Speed Drug Development Timelines ..............73
Activities Implemented to Speed Drug Development Timelines:
Biomanufacturers vs. CMOs ..............................................................74
3-6 Assay Development ....................................................................................76
Biomanufacturing Assay Required; Biomanufacturers vs CMOs .............77
Biomanufacturing Assays Required: US vs Western Europe ..................78
3-7 Perfusion Operations Issues .....................................................................80
3-8 Discussion: Industry Trends and Issues .................................................82
Budget Shifts............................................................................................82
Industry Growth and Adaptation...............................................................82
Cost Cutting Trends ................................................................................83
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TABLE OF CONTENTS
Trends in Assay Development .................................................................83

Trends in Speeding Drug Timelines .........................................................84
CHAPTER 4: Capacity Utilization ................................................. 87

4-1 Capacity Utilization Trends ........................................................................87
Capacity Utilization Definitions.................................................................87
Relevance of Capacity Utilization ............................................................88
Capacity Utilization in 2011 ......................................................................89
Capacity Utilization Changes Since 2004 ...............................................91
Average Growth Rate in Capacity Utilization, 2006-2011 ......................93
4-2 Capacity Utilization: CMOs vs. Biotherapeutic Developers ....................95
4-3 Capacity Utilization: US vs. Western European Manufacturers ..............97
4-4 Respondents’ Current Total Production Capacity....................................99
Mammalian Cell Culture...........................................................................99
Estimated Bioreactor Capacity Distribution, Biotherapeutic
Developers and CMOs ....................................................................103
Contract Manufacturing..........................................................................103
Microbial Fermentation Capacity ...........................................................107
Yeast Production Capacity .....................................................................108
Insect Cells Production Capacity ...........................................................109
4-5 Discussion: Current State of Capacity Utilization .................................110
Future Capacity Issues .......................................................................... 112
4-6 Range of Titres for MAb Production........................................................114
Annual Mab Titre Change, 2008-2011 ................................................... 116
4-7 Discussion: Capacity and Industry Trends .............................................118
Capacity Utilization ................................................................................ 118
CHAPTER 5: Current Capacity Constraints .....................................121

5-1 Current Capacity Constraints ..................................................................121
Factors Creating Future Capacity Constraints .......................................121
Respondents Experiencing No Capacity Constraints ............................124
Respondents’ Perception of Capacity Constraints, 2004-2011 ..............124
Perception of Capacity Constraints: Biotherapeutic
Developers vs. CMOs .....................................................................127
Capacity Constraints: US vs. European Biotherapeutic
Developers & CMOs .......................................................................128
5-2 Expected Capacity Constraints ...............................................................131
Respondents’ Expectations of Capacity Constraints in
the Next Five Years ..........................................................................131
Expected Capacity Constraints by 2015: Comparing
2004 to 2011 Data ............................................................................134
©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED xiii
Expected Capacity Constraints by 2015: CMOs vs.

Biotherapeutic Developers ..............................................................137
Expected Capacity Constraints by 2015: US vs. Western Europe .......139
5-3 Factors Impacting Future Production Capacity .....................................140
Factors Creating Future Capacity Constraints .......................................140
Factors Creating Future Capacity Constraints, 2008 vs. 2011 ..............143
Factors Creating Future Capacity Constraints: Biotherapeutic
Developers vs CMOs .......................................................................146
CMO’s Capacity Bottleneck Projections, in Retrospect .........................148
Biotherapeutic Capacity Bottleneck Projections, in Retrospect .............149
Factors Creating Capacity Constraints: US vs. Western
European Respondents....................................................................151
5-4 Key Areas to Address to Avoid Future Capacity Constraints ..............153
Avoiding Capacity Constraints ...............................................................153
Analysis of Areas to Avoid Capacity Constraints: Changing
Perspectives, 2006-2011 ..................................................................155
General Comments for Reducing Capacity Constraints ........................158
Key Areas to Address to Avoid Capacity Constraints:
U.S. vs Western Europe ...................................................................162
5-5 Discussion .................................................................................................164
CHAPTER 6:Future Capacity Expansions .......................................169

6-1 Planned Future Capacity Expansions.....................................................169
Planned Future Capacity Expansions, 2009 vs. 2015 ...........................170
Planned Future Capacity Expansions by 2015;
CMOs vs. Biotherapeutic Developers ..............................................173
Planned Five-Year Capacity Expansions; US vs. Western
European Manufacturers ..................................................................176
Planned Future Capacity Expansions of >100%....................................179
CHAPTER 7: Outsourcing Trends in Biopharmaceutical Manufacturing ..181

Why Outsource? ....................................................................................181
Critical Outsourcing Operations .............................................................182
Relating Outsourcing to Workforce Reduction .......................................182
Strategic Manufacturing Planning ..........................................................183
New Outsourcing Process & Risk Analysis ............................................185
Future Projections ..................................................................................185
Collaborative Outsourcing......................................................................186
7-1 Current Outsourcing, by Production System .........................................187
Summary of Findings: ...........................................................................187
Facilities Currently Outsourcing No Production
(All Production “In-house”), 2006-2011.............................................189
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TABLE OF CONTENTS
7-2 Future Outsourcing ..................................................................................192

Biotherapeutic Developers’ Outsourcing,
2015 Projections, by System ............................................................192
Biotherapeutic Developers Outsourcing Some Production in 2015 .......195
7-3 Outsourced Activities in Biopharmaceutical Manufacturing ................197
Comparison of Biomanufacturers’ Outsourcing, (2010-2011) ................200
Increased Outsourced Activities, 24-month Projections ........................202
Outsourcing Activities Projected at ‘Significantly Higher Levels’,
Comparison of 2010 vs 2011 Trends ................................................204
Average Percentage of Activities Outsourced Today .............................206
Comparison of outsourcing activities, 2010 vs 2011 ..............................208
7-4 Critical Outsourcing Issues .....................................................................211
Selecting a CMO: 2011 ......................................................................... 211
Selecting a CMO, 2006-2011 ...............................................................214
Changes in Critical Issues when Considering a CMO, 2008-2011 ........216
CMOs’ Problems with Clients.................................................................218
CMOs’ Problems with Clients, Trends....................................................221
7-5 Country Selections for International Outsourcing of
Biomanufacturing .....................................................................................223
US vs Western European Respondents’ Outsourcing Destinations ......225
Western European Respondents’ Outsourcing Destinations .................229
5-Year Projection for Biomanufacturing International
Outsourcing/Off-shoring ...................................................................233
5-Year Projection for Biomanufacturing International
Outsourcing/Off-shoring ...................................................................234
Respondent Comments: ........................................................................234
7-6 Discussion ................................................................................................235
1. Global situation for outsourcing .........................................................235
2. Trends to cut costs .............................................................................235
3. Role of new technologies with impact on outsourcing .......................236
4. Competitive Situation with Impact on outsourcing .............................236
5. Trends to form consortiums around outsourcing options ...................236
6. Future of biologics mfg outsourcing ...................................................236
©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED xv
CHAPTER 8: Disposables and Single-Use Systems in

Biopharmaceutical Manufacturing .............................................239
8-1 Use of Disposables and Single-Use Systems ........................................239
Disposables Applications in Biopharmaceutical Manufacturing .............240
Trends in Disposable Applications: 2006-2011 ......................................242
Annual Growth Rate for Disposables Market Penetration / Usage ........244
6-year Growth in Disposables Applications, Percentage-point Gains ....248
Disposable Use by Stage of Production/Application .............................249
Growth in the use of disposable systems ..............................................250
Newly Introduced Disposable Applications ............................................252
Leachables and Extractables .................................................................256
Cost Conscious L&E Testing ..................................................................256
Use of Disposables: CMOs vs. Biotherapeutic Developers ..................258
8-2 Reasons for Increasing Use of Disposables & Single-Use Systems ...261
Reasons for Increased Use of Disposables, 2006 through 2011 ..........263
Summarizing trends: ..............................................................................263
Reasons for Increased Use of Disposables:
Biotherapeutic Developers vs CMOs ...............................................266
Single Most Critical Reason for Increasing the Use of Disposables ......269
8-3 Factors That May Restrict Use of Disposables .....................................271
Factors That May Restrict Use of Disposables: Trends 2006-2011 .......273
Factors that May Restrict Use of Disposables: CMO’s vs.
Biotherapeutic Developers ...............................................................276
Most Critical Reasons for Restricting Use of Disposables .....................279
Most Important Reasons for Not Increasing Use of
Disposables, 2008-2011 ..................................................................280
Most Important Reasons for Restricting Use of Disposables:
Biotherapeutic Developer vs.CMO ..................................................282
Top Reasons for Not Increasing the Use of Disposables: US vs.
European Respondents....................................................................284
8-4 Standards Setting for Disposable, Single-use Systems .......................287
Design and Engineering Standards Settings .........................................287
Leachables and Extractables Standards Settings .................................288
Component Manufacturing Control (Quality) Standards Settings ..........289
Organizations from Which End Users Expect Standards Settings ........290
8-5 Current Budgets for Disposable Systems ..............................................294
Budgets for Disposable Systems, 2007-2011 ........................................296
Annual Growth Rate in Budgets for Single-use Components 2007-2011298
Data Findings, CAGR ............................................................................298
Current Budget for Disposables: CMO’s vs.
Biotherapeutic Developers ...............................................................301
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TABLE OF CONTENTS
8-7 Disposable Bioreactor Attributes ............................................................304

Waste Disposal of Single-use Devices (2010 Data) ..............................307
Comments in 2010 regarding Waste Disposal Issues: ..........................307
Comments in 2009 regarding Waste Disposal Issues: ..........................308
8-8 Satisfaction with Vendors of Disposables for
Biopharmaceutical Manufacturing ..........................................................311
8-9 Discussion ................................................................................................314
The Expanding Use of Single-use Devices............................................314
Current Markets .....................................................................................314
Safety Concerns with Disposables ........................................................315
Summary................................................................................................315
CHAPTER 9: Downstream Purification .........................................323

9-1 Impact of Downstream Processing on Capacity ....................................323
Impact of Downstream Processing on Capacity, Biopharmaceutical
Developers vs. CMOs .....................................................................327
Impact of Downstream Processing on Capacity, US vs. Western
European Biomanufacturers .............................................................329
9-2 Specific Purification Step Constraints....................................................332
Changes in Impact on Capacity of Purification Steps, 2008-2011 .........333
Specific Purification Step Constraints, US vs. Western European
Biomanufacturers .............................................................................334
9-3 Downstream Purification Issues Facing the Industry Today ...............336
Protein A and Alternatives ......................................................................336
Changes in Perception of Protein A and Alternatives.............................337
Protein A Downstream Purification Issues, US vs Western Europe .......339
9-4 Problems in Downstream Purification ....................................................340
9-5 New Downstream Processing Technologies ..........................................343
New Downstream Processing Solutions; 2010 – 2011 ..........................345
New Downstream Processing Technologies; Biotherapeutic
Developers vs. CMOs ......................................................................346
New Downstream Processing Technologies; US vs Western Europe ...348
9-6 Improvements to Downstream Operations.............................................350
Comparison of New Downstream Technology Investigations;
Biomanufacturers vs CMOs .............................................................351
Comparison of New Downstream Technology Investigations;
US vs W. Europe vs ROW ................................................................352
9-7 Discussion ................................................................................................354
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CHAPTER 10: Quality Issues, Batch Failures, and PAT in

Introduction ............................................................................................357
10-1 Process Analytical Technology(2010 Data) ..........................................358
PAT Initiatives for Existing Processes (2010 Data) ................................358
10-2 Hurdles to Implementing Process Analytical
Technology, 2008-2011 ...........................................................................361
PAT Adoption Will Increase ....................................................................363
10-3 Batch Failure Frequency in Biopharmaceutical Manufacturing .........366
10-4 Primary Cause of Batch Failures and Percentages of Failures ..........369
10-5 Quality Problems Traced to Vendors in Biopharmaceutical
Manufacturing .........................................................................................373
10-6 Automation Implementation ..................................................................377
Comparison of Implementation Plans 2009 - 2011 ................................378
10-7 Quality Initiative Implementation...........................................................381
Comparison of Quality Initiative Implementation, 2009 - 2011 ...............383
10-9 Global Quality Supply Management......................................................385
Global Quality Supply Management ......................................................386
US vs W. European Global Quality Supply Management ......................388
10-10 Effect Of Cost-Cutting on Overall Quality Operations .....................392
CMOs Impact of Cost Cutting on Quality Manufacturing .......................393
US vs Western European Impact of Cost Cutting on
Quality Manufacturing ......................................................................395
10-11 Discussion ............................................................................................396
CHAPTER 11: Hiring, Employment Growth, and Training in

Introduction ............................................................................................397
11-1 Hiring in 2011 ...........................................................................................398
11-2 Hiring in 2015 ...........................................................................................399
11-3 Hiring Challenges Today .........................................................................401
Hiring Difficulties; 2010 vs 2011 .............................................................403
Hiring Difficulties: US vs Western Europe ..............................................406
11-4 Training in Biopharmaceutical Manufacturing .....................................409
Changes in Training for New Manufacturing Employees, 2009-2011 .... 411
11-5 Global Initiatives .....................................................................................412
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TABLE OF CONTENTS / FIGURES AND TABLES
CHAPTER 12:Suppliers to Biopharmaceutical Manufacturing

and Life Sciences .................................................................415
Introduction ............................................................................................415
12-1 Demographics ..........................................................................................415
Areas of Involvement .............................................................................415
Location of Vendor Sales ......................................................................418
Respondents’ Primary Job ....................................................................420
12-2 Growth Rate of Sales by Suppliers .......................................................421
Average Industry Growth Rate, Distribution ...........................................421
Average Industry Growth Rate, By Segment .........................................424
Vendor Sales Growth Rate, by Industry Segment, 2007 to 2011 ...........425
Overall Vendor Sales Growth, 2007-2011 ..............................................427
Vendor Annual Sales, Distribution..........................................................429
12-3 Discussion: Industry Growth Rates ......................................................430
12-4 Budget Issues and Problems Faced by Industry Supplier...................431
Budget Challenges in 2011 ....................................................................431
Vendor Average Budget Changes for 2009 -2011..................................433
Vendor Pricing Changes ........................................................................434
Future Price Changes for 2012 ..............................................................435
CMO Price Changes .............................................................................437
Average CMO Pricing Shift, 2010-2011 .................................................439
12-5 Cost Cutting Actions by Vendors ...........................................................441
Cost Cutting Actions, By Segment .........................................................442
12-6 Problems Faced by Vendors ...................................................................443
Problems Faced by Vendors’ Clients .....................................................444
Vendor Expansion Plans for 2011 ..........................................................446
Biopharma Vendor Business Trends, 2010 vs 2011 ..............................448
Top New Technology Areas in Development by Vendors .......................449
Other NPD activities:..............................................................................451
12-6 Discussion: Supplier Issues .................................................................453
12-7 Sales Staff Training .................................................................................455
Days of Training Provided .....................................................................455
Areas where Training May Help Sales Staff Perform .............................456
Areas where Training May Help Sales Staff Perform,
Trends 2010 vs 2011 ........................................................................458
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F I G U R E S A N D TA B L E S :
Fig 1.1: FDA Approvals of New Biopharmaceutical Products 1982-2010................ 2
Fig 1.2: Investigational Drugs: Large Molecule (Protein Therapeutics),
Worldwide, March 2011 vs March 2010 ...................................................... 4
Fig 1.3: Current Worldwide Pipeline & Launched Products,
Large Molecules, March 2011 ..................................................................... 8
Fig 2.1: Area of Involvement in Biopharmaceutical Manufacturing ........................ 24
Fig 2.2: Area of Involvement in Biopharmaceutical Manufacturing, 2010 vs 2011 25
Fig 2.3: Respondents’ Job Responsibilities............................................................ 26
Fig 2.4: Facility Location ......................................................................................... 27
Fig 2.5: Facility Location, by Region....................................................................... 28
Fig 2.6: Biopharmaceutical Manufacturing Systems, (2007-2011) Trends............. 29
Fig 2.7: Phase of Development of Surveyed Respondents ................................... 30
Fig 2.8: Distribution of Employees at Facility, and Organization ............................ 31
Fig 2.9: Distribution of Total Batches Run at Facility Last Year,
by Scale of Production............................................................................... 33
Fig 3.1: Biomanufacturers’ Budget Shifts for 2011 ................................................. 36
Fig 3.2: Approximate Average Change in Biomanufacturers’ Budgets for 2011 ... 37
Fig 3.3: Approximate Average Change in Biomanufacturers’ Budgets for 2011 ... 39
Fig 3.4: Operational Changes Due to Recent Global Economics .......................... 42
Fig 3.5: Operational Changes Due to Recent Global Economics, 2011 vs 2010... 43
Fig 3.6: Operational Changes Due to Recent Global Economics;
Biotherapeutic developers vs CMO’s ........................................................ 45
Fig 3.7: Operational Changes Due to Recent Global Economics;
US vs Western Europe ............................................................................... 47
Fig 3.8: New Product Development Focus Areas ................................................... 52
Fig 3.9: New Product Development Focus Areas, 2011 vs 2010 ........................... 55
Fig 3.10: New Product Development Areas of Interest:
Biotherapeutic Developers vs CMO’s ........................................................ 57
Fig 3.11: New Product Development Areas of Interest:
US vs Western Europe and ROW .............................................................. 59
Fig 3.12: Factors in Biomanufacturing Performance Creating “Significant”
or “Some” Improvements ........................................................................... 61
or “Some” Improvements: 2011 vs 2010 ................................................... 63
or “Some” Improvements: Biomanufacturers Vs CMOs ............................ 67
or “Some” Improvements: US Vs Western Europe Vs Rest of World ......... 69
Fig 3.16: Cost-Cutting Changes: Actions Undertaken During Past 12 Months ........ 71
Fig 3.17: Cost-Cutting Changes, Outsourced Jobs, by Segment, and Geography . 72
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Fig 3.18: Activities Implemented to Speed Drug Development Timelines ............... 73

Fig 3.19: Activities Implemented to Speed Drug Development Timelines;
Biomanufacturers vs CMOs ....................................................................... 75
Fig 3.20: Biomanufacturing Assay ‘Areas’ Urgently Requiring New,
Improved Testing Methods ........................................................................ 76
Improved Testing Methods; Biomanufacturers vs CMOs .......................... 77
Improved Testing Methods; US vs Western Europe .................................. 79
Fig 3.23: Perfusion Operations Issues: Perfusion vs Batch-Fed
Processes (Note: 2010 Data)..................................................................... 81
Fig 4.1: Capacity Utilization, By System, 2011 ....................................................... 89
Fig 4.2: Capacity Utilization, By System, 2004-2011 ............................................. 92
Fig 4.3: Change in Capacity Utilization, CAGR, 2006-2011 ................................... 94
Fig 4.4: Capacity Utilization, By System, Biotherapeutic Developer vs CMOs ...... 96
Fig 4.5: Capacity Utilization By System, US vs. Western Europe ........................... 98
Fig 4.6: Current Production Capacity Distribution, Mammalian Cell Culture ........ 101
Fig 4.7: Estimated Bioreactor Capacity Distribution, by Biotherapeutic
Developer (2006 vs 2010) ....................................................................... 105
Fig 4.8: Estimated Bioreactor Capacity Distribution, by Contract Manufacturing
Organizations (CMO), 2006, vs 2010, vs 2011........................................ 106
Fig 4.9: Current Production Capacity Distribution, Microbial Fermentation ......... 107
Fig 4.10: Current Production Capacity Distribution, Yeast ..................................... 108
Fig 4.11: Current Production Capacity Distribution, Insect Cells ........................... 109
Fig 4.12: Mammalian Cell Culture Capacity Estimates 2003-2011 ........................ 111
Fig 4.13: Microbial Fermentation Capacity Estimates 2003-2011 .......................... 111
Fig 4.14: Range of Titres for Mabs Obtained at Various Production
Scales, Distribution .................................................................................. 115
Fig 4.15: Annual Average Mab Titre Increase, 2008-2011 ..................................... 116
Fig 5.1: Capacity Constraints, by Stage of Production......................................... 122
Fig 5.2: Capacity Constraints, 2004 through 2011 ............................................... 125
Fig 5.3: Capacity Constraints Trends, 2004-2011 ................................................ 126
Fig 5.4: Capacity Constraints, Biotherapeutic Developers vs CMOs ................... 127
Fig 5.5: Capacity Constraints, US vs. Europe ...................................................... 130
Fig 5.6: Expectations of Capacity Constraints; by Stage of Production;
five-year Projections ................................................................................ 132
Fig 5.7: Expectations of Capacity Constraints: Five-year Projections
Made in 2004-2011 .................................................................................. 135
Fig 5.8: Expectations of Capacity Constraints: Five-year Projections
Made in 2004-2011 (Trend Line).............................................................. 136
Fig 5.9: Five-year Projections for Capacity Constraints: Biotherapeutic
Developers vs CMOs ............................................................................... 137
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Fig 5.10: Five-year Projections for Capacity Constraints: US vs Western Europe.. 139
Fig 5.11: Factors Creating Future Capacity Constraints ........................................ 141
FIG 5.12: Factors Creating Future Capacity Constraints, 2008-2011 ..................... 144
Fig 5.13: Factors Creating Future Capacity Constraints, CMOs vs
Biotherapeutic Developers ..................................................................... 147
Fig 5.14: Factors Creating Future Capacity Constraints, US vs Western
European Biomanufacturers .................................................................... 152
Fig 5.15: Key Areas to Address to Avoid Capacity Constraints ............................ 154
Fig 5.16: Key areas to Address to Avoid Capacity Constraints; 2006-2011 .......... 156
Fig 5.17: Key areas to Address to Avoid Capacity Constraints;
Biomanufacturers vs CMOs ..................................................................... 160
Fig 5.18: Key areas to Address to Avoid Capacity Constraints;
U.S. vs Western Europe ........................................................................... 163
Fig 6.1: Industry Average Planned Production Increase by 2015 ........................ 170
Fig 6.2: Planned Future Capacity Expansion: 5-year Estimates,
2009 through 2015................................................................................... 171
Fig 6.3: Planned Future Capacity Expansion: 5-year Estimates,
2009 - 2015 (Trend Line).......................................................................... 172
Fig 6.4: Planned Future Capacity Expansion: 5-year Estimates;
Biotherapeutic Developers vs CMOs ...................................................... 175
Fig 6.5: Planned Future Capacity Expansion: 5-year Estimates, 2009 - 2015,
US vs Western Europe ............................................................................. 177
Fig 6.6: Percent of Respondents Projecting Production Increases of
over 100% by 2015; 4-year Trend............................................................ 179
Fig 7.1: Current Percent Production Outsourced; by System, 2009..................... 188
Fig 7.2: Biopharmaceutical Manufacturing Facilities Outsourcing
NO Production, 2006-2011 ...................................................................... 190
Fig 7.3: Biopharmaceutical Manufacturing Facilities Outsourcing
NO Production, 2006-2011 (Trend Line ................................................... 191
Fig 7.4: Future Outsourcing: Percent Production Outsourced;
by System, in 2015 .................................................................................. 193
Fig 7.5: Five-year Projections: Percent Biotherapeutic Developers
Planning to Outsource at Least Some Production; Projections
made 2007-2011 ..................................................................................... 196
Fig 7.6: Percent of Biomanufacturers Outsourcing at Least Some
Activity Today ........................................................................................... 198
Fig 7.7: Percent of Biomanufacturers Outsourcing at Least Some Activity,
(2010-2011) ............................................................................................. 201
Fig 7.8: Outsourcing Activities Projected to be Done at ‘Significantly Higher
Levels’ in 2 Years ..................................................................................... 203
Fig 7.9: Outsourcing Activities Projected to be Done at ‘Significantly Higher
Levels’ in 2 Years, 2010 vs 2011 Trend ................................................... 205
Fig 7.10: Current Outsourcing: Average Percentage of Activity
Outsourced Today ................................................................................... 207
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Fig 7.11: Current Outsourcing: Average Percentage of Activity Outsourced,

2010-2011 ................................................................................................ 209
Fig 7.12: Outsourcing Issues: BioManufacturing by Contract
Manufacturing Organizations .................................................................. 212
Fig 7.13: Important Outsourcing Issues: BioManufacturing by Contract
Manufacturing Organizations, Trends 2005-2009 ................................... 215
Fig 7.14: Important Outsourcing Issues: Response Shifts Over Time 2008-2011,
Percentage Point Differences .................................................................. 216
Fig 7.15: Most Common Mistakes Biopharmaceutical Sponsors
Make with their CMOs.............................................................................. 220
Fig 7.16: Most Common Mistakes Biopharmaceutical Sponsors
Make with their CMOs.............................................................................. 221
Fig 7.17: Country Selections as Destination for International Outsourcing of
BioManufacturing (All Respondents) ....................................................... 224
Fig 7.18: Percent U.S. Respondents Considering Country as ‘Possible’
Outsourcing Destination .......................................................................... 226
Fig 7.19: Percent U.S. Respondents Considering Country as “Strong Likelihood”
or “Likelihood” as Outsourced Capacity Destination .............................. 227
Fig 7.20: Percent Western European Respondents Considering Country
as “Strong Likelihood” or “Likelihood” as Outsourced
Capacity Destination................................................................................ 231
Fig 7.22: Percent of Biomanufacturing Operations Off-shored
(International Outsourcing) within 5 Years. ............................................. 233
Fig 7.23: Estimated % Operations Done as International
Outsourcing/Off-shoring during Next 5 Years.......................................... 234
Fig 8.1: Usage of Disposables in Biopharmaceutical manufacturing,
any Stage of R&D or Manufacture ........................................................... 241
Fig 8.2: Usage of Disposables in Biopharmaceutical manufacturing,
any Stage of R&D or Manufacture; 2006-2011 ........................................ 243
Fig 8.3: Average Annual Growth Rate, Disposables, 2006-2011 ......................... 247
Fig 8.4: 6-Year Percentage-Point Change in First-Usage of
Disposables, 2006-2011 .......................................................................... 248
Fig 8.5: Usage of Disposables in Biopharmaceutical manufacturing, by
Stage of Manufacture (R&D through Commercial Manufacture) ............ 251
Fig 8.6: Newly Introduced Disposables, Past 12 Months ..................................... 253
Fig 8.7: Current Issues: Leachables and Extractables in Disposable Devices .... 257
Fig 8.8: Usage of Disposables in Biopharmaceutical Manufacturing;
Biotherapeutic Developer vs CMO .......................................................... 259
Fig 8.9: Reasons for Increasing Use of Disposable System
Components in 2011................................................................................ 262
Fig 8.10: Reasons for Increasing Use of Disposables 2006-2011 ......................... 264
Fig 8.11: Reasons for Increasing Use of Disposable System Components,
Fig 8.12: Most Critical Reason for Increasing Use of Disposables ........................ 270
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Fig 8.13: Reasons for Restricting Use of Disposables .......................................... 272

Fig 8.14: Factors Restricting Use of Disposables, 2006-2011 ............................... 275
Fig 8.15: Factors Restricting Use of Disposables in Biotherapeutic
Developer vs CMO .................................................................................. 277
Fig 8.16: Top Reasons for Not Increasing Use of Disposables, 2011 .................... 279
Fig 8.17: Top Reasons for Not Increasing Use of Disposables, 2008-2011 ........... 281
Fig 8.18: Top Reasons for Not Increasing Use of Disposables,
Biotherapeutic Developer vs CMO .......................................................... 283
Fig 8.19: Top Reasons for Not Increasing Use of Disposables,
Fig 8.20: Standards Setting for Design and Engineering;
Organizations Expected to Set Standards .............................................. 287
Fig 8.21: Standards Setting for Design Leachables and Extractables;
Fig 8.22: Standards Setting for Component Manufacturing Control (Quality);
Fig 8.23: Standards Setting for Component Manufacturing Control (Quality);
Fig 8.24: Average Budget Per Facility, Single-use Disposable
System Components................................................................................ 295
Fig 8.25: Average Budget, Single-use Disposable System
Components, 2007 vs 2010 ..................................................................... 297
Fig 8.26: CAGR: Growth Rate in Budget on Single-use / Disposable
System Components 2007-2011 (by device) .......................................... 299
Fig 8.27: Average Disposables Budget Per Facility, Disposable
Systems; Biotherapeutic Developers vs CMOs ..................................... 302
Fig 8.28: Disposable Bioreactor Attributes Considered “Very Important” .............. 305
Fig 8.29: Disposable Bioreactor Attributes Considered “Very Important”,
2010 vs 2011 ........................................................................................... 306
Fig 8.30: Impact of Waste Disposal for Disposables (Note: 2010 data)................. 309
Fig 8.31: Single-Use Product Vendor Satisfaction Factors ..................................... 312
Fig 9.1: Impact of Downstream Processing on Overall Capacity ......................... 325
Fig 9.2: Impact of Downstream Processing on Overall Capacity;
Fig 9.3: Impact of Downstream Processing on Overall Capacity;
Fig 9.4: Impact on Capacity of Depth, Chromatography and
UF Purification Steps ............................................................................... 332
Fig 9.5: Impact on Capacity of Purification Steps: Experiencing at
“Significant” or “Severe” Constraints, 2008 - 2011 .................................. 333
Fig 9.6: Impact on Capacity of Purification Steps, U.S., vs Western Europe ....... 334
Fig 9.7: Issues Regarding Protein A Usage ......................................................... 336
Fig 9.8: Issues Regarding Protein A Usage, 2009 -2011 ..................................... 337
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Fig 9.9: Issues Regarding Protein A Usage; US vs. Western Europe .................. 339
Fig 9.10: Problem Areas in Downstream Operations, 2007 vs 2009
(Data from 2010 Study)........................................................................... 341
Fig 9.11: New Downstream Processing Solutions in 2010 ..................................... 344
Fig 9.12: New Downstream Processing Solutions; 2010 - 2011 ............................. 345
Fig 9.13: New Downstream Processing Solutions in 2010;
Biotherapeutic Dev. vs CMO ................................................................... 347
Fig 9.14: New Downstream Processing Solutions in 2011;
US vs. Western Europe ............................................................................ 349
Fig 9.15: Improving Downstream Operations ......................................................... 350
Fig 9.16: Improving Downstream Operations; Biomanufacturers vs CMOs ........... 351
Fig 9.17: Improving Downstream Operations (US Vs Western Europe Vs ROW)... 352
Fig 10.1: Implementation of Process Analytical Technology (PAT) for New
Biomanufacturing Processes, 2009 vs 2010 (2010 Data) ....................... 359
Fig 10.2: Hurdles Hindering Implementation of PAT (2008 - 2011) ........................ 362
Fig 10.3: Batch Failure Frequency Distribution, 2009 – 2011 ................................. 367
Fig 10.4: Average Rates of Failure, by Primary Cause, and Phase of
Manufacture, 2011 ................................................................................... 370
Fig 10.5: Average Rates of Failure, by Primary Cause, and Phase of
Manufacturing 2009 - 2011 (Commercial Manufacture) .......................... 371
Fig 10.6: Quality problems traced to vendors ........................................................ 374
Fig 10.7: Automation Technologies Implemented, or to be Implemented in 2011 . 377
Fig 10.8: Automation Technologies to be Implemented; Comparing 2009 - 2011 . 378
Fig 10.9: Quality Initiative Implemented Currently, or within Next 12 Months......... 381
Fig 10.10: Quality Initiative to be Implemented in “Next 12 Months”,
Comparing 2009 - 2011 ........................................................................... 383
Fig 10.11: Global Quality Supply Management ........................................................ 385
Fig 10.12: Global Quality Supply Management (Biomanufacturers vs CMOs) ........ 387
Fig 10.13: Global Quality Supply Management (US vs W. Europe).......................... 389
Fig 10.14: Cost Cutting Impact on Quality................................................................ 392
Fig 10.15: Cost Cutting Impact on Quality (Biomanufacturers Vs CMOs) ................ 394
Fig 10.16: Cost Cutting Impact on Quality (US vs Western Europe) ........................ 395
Fig 11.1: New Hires in Biopharmaceutical Manufacturing (2011) .......................... 398
Fig 11.2: New Hires in Biopharmaceutical Manufacturing (2015) .......................... 399
Fig 11.3: Areas Where Hiring Difficulties Exist in Biopharmaceutical Operations .. 402
Fig 11.4: Areas Where Hiring Difficulties Exist in Biopharmaceutical
Operations; 2010 vs 2011........................................................................ 404
Fig 11.5: Areas Where Hiring Difficulties Exist in Biopharmaceutical
Operations, US vs. Western Europe ........................................................ 407
Fig 11.6: Training for New Operations/Manufacturing Employees ......................... 410
Fig 11.7: Changes in Training for New Operations/Manufacturing Employees ...... 411
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Fig 11.8: Global Health Interest .............................................................................. 412

Fig 12.1: Area of Biopharmaceutical Involvement, Vendor .................................... 417
Fig 12.2: Area of Biopharmaceutical Involvement, Vendors, 2011 vs 2010 ........... 417
Fig 12.3: Geographic Locations in which Vendors Currently
Actively Sell Products or Services ........................................................... 418
Fig 12.4: Respondents’ Primary Job Function ........................................................ 420
Fig 12.5: Biopharmaceutical Supply Market Segment Sales
Growth Distribution .................................................................................. 422
Fig 12.6: Average Annual Vendor Segment Sales Growth Rates, 2011 ................. 424
Fig 12.7: Average Annual Vendor Sales Growth Rate,
2007 – 2011, by Segment ........................................................................ 425
Fig 12.8: Average Annual, Vendor Sales Growth Rate, 2007 – 2011 ..................... 427
Fig 12.9: Average Annual Vendor Sales Trend Line, 2007 - 2011, by Segment..... 428
Fig 12.10: Vendors’ Approx Annual Sales to Biopharmaceutical Segment % ......... 429
Fig 12.11: Vendors’ Average Budget Change for 2011............................................ 431
Fig 12.12: Vendors’ Average Budget Change for 2009 - 2011, Summary ............... 433
Fig 12.13: Vendors’ Average Pricing Changes in 2011 ............................................ 434
Fig 12.14: Vendors’ Average Pricing Changes, 2009 Actual - 2012 Projected ........ 435
Fig 12.15: CMOs Service Price Shifts in 2011, Distribution ...................................... 437
Fig 12.16: Average CMOs Service Price Shifts in 2010 ........................................... 438
Fig 12.17: Average CMOs Service Price Shifts 2010 vs 2011.................................. 439
Fig 12.18: Actions undertaken to reduce overall costs, past 12 months ................. 441
Fig 12.19: Actions undertaken to reduce overall costs in past 12 months,
By Segment ............................................................................................. 442
Fig 12.20: Problems Faced by All Suppliers ........................................................... 443
Fig 12.21 (Fig 10.6 Recap): Biomanufacturers’ and CMOs Quality
Problems Traced to Vendors.................................................................... 444
Fig 12.22: Biopharma Business and Marketing Plans, 2011 .................................... 446
Fig 12.23: Biopharma Business and Marketing Plans, 2010 vs 2011 ...................... 448
FIG 12.24: Top New Technologies or New Product Development Areas .................. 450
Fig 12.25: Days of Sales Staff Training Provided ...................................................... 455
FIG 12.26: Areas Where Training May Help Sales Staff Perform Better;
All Respondents vs Sales Reps Only ...................................................... 456
FIG 12.27: Areas Where Training May Help Sales Staff Perform
Better; 2010 vs 2011 ................................................................................ 458
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TA B L E S
Table 1.1: Biologics (Large Molecule), Worldwide, through March 2011 .................... 5
Table 1.2: Summary All Therapeutics vs Biologics (Large Molecule),
Worldwide, through March 2011 (Comparing 2008-2010) .......................... 6
Table 1.3: Worldwide Pipeline, Large Molecules, 2011 ............................................... 7
Table 1.4: Summary of Worldwide Biopharmaceutical Revenue by
Product Class, 2007 and 2010 estimates .................................................. 11
Table 1.5: Biopharmaceutical Blockbusters: >$1 billion revenue, and
Expression Systems/Host Cells (2010 vs 2009) ........................................ 12
Table 1.6: Biopharmaceutical Markets ñ Products and Revenue by Class ............... 15
Table 1.7: Monoclonal Antibody Therapeutic Products Revenue & Approvals.......... 15
Table 1.7: Expression Systems/Host Cells for U.S./EU-Marketed
Cultured Biopharmaceuticals .................................................................... 19
Table 3.1: Areas of Significant Projected Budget Increases for Biomanufacturing,
Past Three Years: ....................................................................................... 38
Table 4.1: Distribution of Mammalian Cell Culture Capacity in 2011,
Product Manufacturers ........................................................................... 104
Table 4.2: Distribution of Mammalian Cell Culture Capacity Among Contract
Manufacturing Organizations (CMOs), 2011 data................................... 106
Table 4.3: Compound Annual Change in Mab Titre, 2008-2011 .............................. 117
Table 7.1: Percent of US-based Respondents Indicating Country as a
“Strong Likelihood” or “Likelihood” as Outsourcing
Destination, 2009-2011 ........................................................................... 228
Table 9.1: Percent experiencing ‘Serious’ or ‘Some’ capacity problems due to
downstream processing 2008-2011 ....................................................... 327
Table 9.2: Percent US vs Western Europe facilities experiencing ‘Serious’
capacity problems due to downstream processing, 2009-2011 ............. 329
Table 9.3: Percent US vs Western Europe facilities experiencing
‘No Downstream Bottlenecks’ due to downstream
processing, 2008-2011 ............................................................................ 329
Table 10-1: Batch Failures, Average Weeks per Failure, per Facility, 2008-2011 ...... 366
Table 12-1: Average Industry Growth Rate, 2007 -2011 ............................................ 421
Table 12.2: Top 14 Areas of biopharma R&D and New Product Development .......... 451
Table 12-3: Average Vendor Sales and Technical Training Days, 2010 - 2011 .......... 455
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OVERVIEW
Market Trends
D espite continuing worldwide economic problems, the biopharmaceutical industry

remains strong, dynamic and growing. Many pharmaceutical companies,
particularly the larger ones, continue their dramatic efforts to reduce costs and increase
internal efficiency, including reducing the number of products in R&D, cutting staff and
outsourcing and pursuing mergers and acquisitions. However, most of these same
pharmaceutical companies continue to increase their involvement in biopharmaceutical
development, manufacture and marketing. Many companies are increasing, or
attempting to increase the number and percentage of biopharmaceutical products (vs.
drugs) they have in active development.
Key developments and trends in 2011 affecting the biopharmaceutical industry include
advances in science, technology, commerce and regulations.
❚ Biopharmaceuticals: Already at 40% of the pharmaceutical R&D pipeline, the
number and percentage of biopharmaceuticals vs. drugs in development will
continue to increase. Biopharmaceuticals offer advantages in development
over drugs. Recombinant proteins and antibodies offer a higher likelihood of
reaching the market, including offering a high degree of selectivity and lower
toxicity. And once biopharmaceuticals enter the market, they generally sell for
higher prices, provide higher profits and profit margins, and are more difficult
than small molecule drugs for others to copy. In fact, some pharmaceutical
companies are getting more involved in biopharmaceutical and generic drug
manufacturing and marketing at the expense of traditional small molecule drugs.
Despite the billions invested in recent years in high throughput screening and
small molecule drug discovery technologies, much like prior investments in
gene sequencing to support pharmaceutical agent discovery, the mainstream
drug industry has had relatively few successfully developed, profitable products
from these efforts.
❚ Biopharma Approvals: 2011 will see a continued healthy number of new
biopharmaceutical products entering the U.S. and other major markets. In
2010, the number of FDA approvals rebounded from a particularly low number
of approvals in 2009, getting back to a level more typical of the rest of the past
decade; and there are currently nearly 60 products with applications either
pending or expected to be filed with FDA in 2011. There are currently about
350 biopharmaceutical products approved in the U.S. This number will grow
significantly in coming years, particularly as multiple biosimilar (and bio-better)
versions of most every established biopharmaceutical enter the market.
©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED xxix
C H A P T E R 3:
EMERGING ISSUES IN
BIOPHARMACEUTICAL
M A N U FA C T U R I N G
3-1 BUDGET ISSUES IN 2011
T
his year, we are continuing to see clear evidence that budgets are bouncing back
in all areas. In fact, our respondents projected only budget increases this year.
This is a change from last year where budgets continued to show decreases in
areas ranging from outsourcing production, hiring new scientific staff, and new facility
construction.
The financing crunch is lightening and respondents are indicating wallets are opening;
however, anecdotally, vendors are indicating that buyers are continuing to be cautious
with their spending. Sales cycles continue to be drawn out, and many end users are
demanding moreINCLUDED
milestoneINperformance
FULL REPORTand risk sharing from suppliers.
Yet the data are clear. More biologics are being approved, more deals are being made,
and spending on all budget areas is up from between 1% and 6%. Even spending on
new capital equipment is expanding. Consistent with this trend, we are finding vendors’
budgets are also up, aside from new facility construction, by as much as 4%. This is a
significant reversal from the past three years (see Chapter 12).
Healthcare segments historically have been relatively insulated from adverse financial
situations, and this year, we continue to see evidence that the economy within this
segment has leveled out, which has resulted in a comparatively rapid up-tick in budget
allocations, especially in areas that improve performance for manufacturing activities,
and areas involving productivity. For example, again this year, budgets are favoring
spending on productivity. This includes internal new technology investments (both up-
and down-stream), and process development and optimization.
And although new hiring for operations and scientific staff are down this year,
operations training to improve efficiency is up once again, (5.2% this year, compared
©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED 35

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Biomfg Report

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8th Annual

Report and Survey of

BioPlan Associates, Inc.

Copyright ©2011 by BioPlan Associates, Inc.

BioPlan Associates, Inc.

Copyright © 2011 by BioPlan Associates, Inc.

All rights reserved, including the right of reproduction in whole or in part

For information on special discounts or permissions contact

Managing Editor: Eric S. Langer

FRONT COVER PHOTOS (L.to R.):

ABOUT THE AUTHORS (ALPHABETICAL)

E. Faye Coggins, Founder and Principal of BioTraction Associates,

Thomas E. Colonna PhD/JD Associate Director BioScience

Alfred C Dadson Jr, Sr Director, Manufacturing Operations,

Nicholas Folger, President, Jobs Board for Life Science

Geoff Hodge, Vice President, FlexFactory® Contract Manufacturing

Wolf Noe, Sr. Consultant with Bioprocess Technology Consultants

Ronald A. Rader, President, Biotechnology Information Institute

Rowena L. Roberts, PhD, Founder and Principal of BioTraction

Storm Lefelar, Consultant, Storm Biotechnology

James Dean Vogel, P.E., Founder and Director, The BioProcess

Scott M. Wheelwright, Ph.D., Founder and Principal, Strategic

CHAPTER 1:Introduction and Discussion..........................................1

CHAPTER 2: Demographics ....................................................... 23

CHAPTER 3:Emerging Issues in Biopharmaceutical Manufacturing ........ 35

Trends in Assay Development .................................................................83

CHAPTER 4: Capacity Utilization ................................................. 87

CHAPTER 5: Current Capacity Constraints .....................................121

Expected Capacity Constraints by 2015: CMOs vs.

CHAPTER 6:Future Capacity Expansions .......................................169

CHAPTER 7: Outsourcing Trends in Biopharmaceutical Manufacturing ..181

7-2 Future Outsourcing ..................................................................................192

CHAPTER 8: Disposables and Single-Use Systems in

8-7 Disposable Bioreactor Attributes ............................................................304

CHAPTER 9: Downstream Purification .........................................323

CHAPTER 10: Quality Issues, Batch Failures, and PAT in

CHAPTER 11: Hiring, Employment Growth, and Training in

CHAPTER 12:Suppliers to Biopharmaceutical Manufacturing

Fig 3.18: Activities Implemented to Speed Drug Development Timelines ............... 73

Fig 7.11: Current Outsourcing: Average Percentage of Activity Outsourced,

Fig 8.13: Reasons for Restricting Use of Disposables .......................................... 272

Fig 11.8: Global Health Interest .............................................................................. 412

D espite continuing worldwide economic problems, the biopharmaceutical industry

3-1 BUDGET ISSUES IN 2011

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