th · 2015. 10. 5. · of Millenniumís biologics pipeline. In this role he pioneered the use of disposable manufacturing systems for the production of monoclonal antibodies and helped

8th Annual

Report and Survey of

Biopharmaceutical Manufacturing

Capacity and ProductionA Study of Biotherapeutic Developers and Contract Manufacturing Organizations

April 2011

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.

associates, inc.

8th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and ProductionA Study of Biotherapeutic Developers and Contract Manufacturing Organizations

April 2011

BioPlan Associates, Inc. 2275 Research Blvd, Suite 500Rockville MD 20850301-921-5979www.bioplanassociates.com

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 contactBioPlan Associates, Inc. at 301-921-5979, or [email protected]

Managing Editor: Eric S. LangerProject Director: Krista MeiselLayout 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.

©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED iii

A C K N O W L E D G M E N TWe 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) ❚

Report and Survey of Biopharmaceutical Manufacturing Capacity and Production

WWW.BIOPLANASSOCIATES.COMiv

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. LangerEditor

©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED v

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 offi ce labs and hospital laboratory environments.

We prepare custom studies, and provide public information our clients require to make informed strategic decisions, defi ne 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.

BioPlan Associates, Inc. 2275 Research Blvd., Suite 500Rockville, MD 20850 USAwww.bioplanassociates.com Tel: 301-921-5979


WWW.BIOPLANASSOCIATES.COMvi

E D I T O 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 purifi cation, blood components, and many other areas.

A B O U T T H E A U T H O R S ( A L P H A B E T I C A L )

E. Faye Coggins, Founder and Principal of BioTraction Associates, LLCMs. 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) certifi cation. 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.

©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED vii

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-profi t Regulatory Affairs Institute. [email protected]

Alfred C Dadson Jr, Sr Director, Manufacturing Operations, XOMA LLCAl 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, IncNick 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.

AUTHORS


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Geoff Hodge, Vice President, FlexFactory® Contract Manufacturing Services, XcellerexGeoffrey 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 fi eld. 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 ConsultantsWolfgang 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 InstituteMr. 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.

©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED ix

Rowena L. Roberts, PhD, Founder and Principal of BioTraction Associates, LLCDr. 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 Purifi cation 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.

AUTHORS


WWW.BIOPLANASSOCIATES.COMx

James Dean Vogel, P.E., Founder and Director, The BioProcess InstituteMr. 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 fi tness 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, StrategicManufacturing 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 fi rms 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 purifi cation 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 offi ce in Shanghai to assist clients in Asia with outsourcing and cGMP compliance.

©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED xi

8th Annual Report and Survey of

Biopharmaceutical Manufacturing

Capacity and Production • April 2011A Study of Biotherapeutic Developers and Contract Manufacturing Organizations

C O N T E N T SOverview ........................................................................... xxix

Market Trends ........................................................................................xxixMarket Potential ...................................................................................xxxiv

Methodology..................................................................... xxxvii

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

The Biopharmaceutical Pipeline ...............................................................3

1-1 U.S. and World Biopharmaceutical and Recombinant Protein/Mab Markets ......................................................................................8

Biosimilars and Bio-betters ......................................................................10BRIC Country Growth ..............................................................................10Expression Systems Today ......................................................................13Biosimilars 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 .......................................................................21CMOs .......................................................................................................21Industry Suppliers ....................................................................................21Government .............................................................................................22


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CHAPTER 2: Demographics ....................................................... 23Respondents’ Area of Involvement ..........................................................23Respondents’ Titles ..................................................................................26Respondents’ Facility Locations ...............................................................27Respondents’ Areas of Biopharmaceutical Manufacturing Operations ....29Respondents’ Production Operations, Phase of Development ................30Employees at Facility ...............................................................................31Batches Run at Facility per Year ..............................................................32

CHAPTER 3:Emerging Issues in Biopharmaceutical Manufacturing ........ 353-1 Budget Issues in 2011 ................................................................................35

Budget Change Comparisons .................................................................38

3-2 Operational Changes in 2011 ....................................................................40Operational Changes: 2011 vs 2010 ........................................................43Operational Changes: Biotherapeutic Developers vs CMOs ...................44Operational Changes: US vs Western Europe ........................................46

3-3 New Product Development Opportunities in 2011 ...................................49New Product Development Focus, 2011 vs 2010 ....................................54New Product Development Areas: Biotherapeutic

Developers vs CMO’s .........................................................................56New Product Development Areas: Biotherapeutic US vs

Western Europe and ROW .................................................................58

3-4 Factors in Biomanufacturing Creating Improvements ............................60Factors Improving Biomanufacturing Performance, 2011 vs 2010 ..........62Factors Improving Biomanufacturing Performance, Biotherapeutic

Developers vs CMOs .........................................................................66Factors Improving Biomanufacturing Performance, US vs

Western Europe, vs ROW ..................................................................68

3-5 Cost-Cutting Actions & Development Timelines .......................................70Cost-Cutting Changes: Specifi c to Outsourcing .......................................72Activities Implemented to Speed Drug Development Timelines ..............73Activities Implemented to Speed Drug Development Timelines:

Biomanufacturers vs. CMOs ..............................................................74

3-6 Assay Development ....................................................................................76Biomanufacturing Assay Required; Biomanufacturers vs CMOs .............77Biomanufacturing Assays Required: US vs Western Europe ..................78

3-7 Perfusion Operations Issues .....................................................................80

3-8 Discussion: Industry Trends and Issues .................................................82Budget Shifts ............................................................................................82Industry Growth and Adaptation ...............................................................82Cost Cutting Trends ................................................................................83

©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED xiii

TABLE OF CONTENTS

Trends in Assay Development .................................................................83Trends in Speeding Drug Timelines .........................................................84

CHAPTER 4: Capacity Utilization ................................................. 874-1 Capacity Utilization Trends ........................................................................87

Capacity Utilization Defi nitions .................................................................87Relevance of Capacity Utilization ............................................................88Capacity Utilization in 2011 ......................................................................89Capacity Utilization Changes Since 2004 ...............................................91Average 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 ....................................99Mammalian Cell Culture ...........................................................................99Estimated Bioreactor Capacity Distribution, Biotherapeutic

Developers and CMOs ....................................................................103Contract Manufacturing ..........................................................................103Microbial Fermentation Capacity ...........................................................107Yeast Production Capacity .....................................................................108Insect Cells Production Capacity ...........................................................109

4-5 Discussion: Current State of Capacity Utilization .................................110Future Capacity Issues .......................................................................... 112

4-6 Range of Titres for MAb Production ........................................................114Annual Mab Titre Change, 2008-2011 ................................................... 116

4-7 Discussion: Capacity and Industry Trends .............................................118Capacity Utilization ................................................................................ 118

CHAPTER 5: Current Capacity Constraints .....................................1215-1 Current Capacity Constraints ..................................................................121

Factors Creating Future Capacity Constraints .......................................121Respondents Experiencing No Capacity Constraints ............................124Respondents’ Perception of Capacity Constraints, 2004-2011 ..............124Perception of Capacity Constraints: Biotherapeutic

Developers vs. CMOs .....................................................................127Capacity Constraints: US vs. European Biotherapeutic

Developers & CMOs .......................................................................128

5-2 Expected Capacity Constraints ...............................................................131Respondents’ Expectations of Capacity Constraints in

the Next Five Years ..........................................................................131Expected Capacity Constraints by 2015: Comparing

2004 to 2011 Data ............................................................................134


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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 .....................................140Factors Creating Future Capacity Constraints .......................................140Factors Creating Future Capacity Constraints, 2008 vs. 2011 ..............143Factors Creating Future Capacity Constraints: Biotherapeutic

Developers vs CMOs .......................................................................146CMO’s Capacity Bottleneck Projections, in Retrospect .........................148Biotherapeutic Capacity Bottleneck Projections, in Retrospect .............149Factors Creating Capacity Constraints: US vs. Western

European Respondents ....................................................................151

5-4 Key Areas to Address to Avoid Future Capacity Constraints ..............153Avoiding Capacity Constraints ...............................................................153Analysis of Areas to Avoid Capacity Constraints: Changing

Perspectives, 2006-2011 ..................................................................155General Comments for Reducing Capacity Constraints ........................158Key Areas to Address to Avoid Capacity Constraints:

U.S. vs Western Europe ...................................................................162

5-5 Discussion .................................................................................................164

CHAPTER 6:Future Capacity Expansions .......................................1696-1 Planned Future Capacity Expansions.....................................................169

Planned Future Capacity Expansions, 2009 vs. 2015 ...........................170Planned Future Capacity Expansions by 2015;

CMOs vs. Biotherapeutic Developers ..............................................173Planned Five-Year Capacity Expansions; US vs. Western

European Manufacturers ..................................................................176Planned Future Capacity Expansions of >100%....................................179

CHAPTER 7: Outsourcing Trends in Biopharmaceutical Manufacturing ..181Why Outsource? ....................................................................................181Critical Outsourcing Operations .............................................................182Relating Outsourcing to Workforce Reduction .......................................182Strategic Manufacturing Planning ..........................................................183New Outsourcing Process & Risk Analysis ............................................185Future Projections ..................................................................................185Collaborative Outsourcing ......................................................................186

7-1 Current Outsourcing, by Production System .........................................187Summary of Findings: ...........................................................................187Facilities Currently Outsourcing No Production

(All Production “In-house”), 2006-2011.............................................189

©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED xv

TABLE OF CONTENTS

7-2 Future Outsourcing ..................................................................................192Biotherapeutic Developers’ Outsourcing,

2015 Projections, by System ............................................................192Biotherapeutic Developers Outsourcing Some Production in 2015 .......195

7-3 Outsourced Activities in Biopharmaceutical Manufacturing ................197Comparison of Biomanufacturers’ Outsourcing, (2010-2011) ................200Increased Outsourced Activities, 24-month Projections ........................202Outsourcing Activities Projected at ‘Signifi cantly Higher Levels’,

Comparison of 2010 vs 2011 Trends ................................................204Average Percentage of Activities Outsourced Today .............................206Comparison of outsourcing activities, 2010 vs 2011 ..............................208

7-4 Critical Outsourcing Issues .....................................................................211Selecting a CMO: 2011 ......................................................................... 211Selecting a CMO, 2006-2011 ...............................................................214Changes in Critical Issues when Considering a CMO, 2008-2011 ........216CMOs’ Problems with Clients .................................................................218CMOs’ Problems with Clients, Trends ....................................................221

7-5 Country Selections for International Outsourcing of Biomanufacturing .....................................................................................223

US vs Western European Respondents’ Outsourcing Destinations ......225Western European Respondents’ Outsourcing Destinations .................2295-Year Projection for Biomanufacturing International

Outsourcing/Off-shoring ...................................................................2335-Year Projection for Biomanufacturing International

Outsourcing/Off-shoring ...................................................................234Respondent Comments: ........................................................................234

7-6 Discussion ................................................................................................2351. Global situation for outsourcing .........................................................2352. Trends to cut costs .............................................................................2353. Role of new technologies with impact on outsourcing .......................2364. Competitive Situation with Impact on outsourcing .............................2365. Trends to form consortiums around outsourcing options ...................2366. Future of biologics mfg outsourcing ...................................................236


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CHAPTER 8: Disposables and Single-Use Systems in Biopharmaceutical Manufacturing .............................................239

8-1 Use of Disposables and Single-Use Systems ........................................239Disposables Applications in Biopharmaceutical Manufacturing .............240Trends in Disposable Applications: 2006-2011 ......................................242Annual Growth Rate for Disposables Market Penetration / Usage ........2446-year Growth in Disposables Applications, Percentage-point Gains ....248Disposable Use by Stage of Production/Application .............................249Growth in the use of disposable systems ..............................................250Newly Introduced Disposable Applications ............................................252Leachables and Extractables .................................................................256Cost Conscious L&E Testing ..................................................................256Use of Disposables: CMOs vs. Biotherapeutic Developers ..................258

8-2 Reasons for Increasing Use of Disposables & Single-Use Systems ...261Reasons for Increased Use of Disposables, 2006 through 2011 ..........263Summarizing 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 .....................................271Factors That May Restrict Use of Disposables: Trends 2006-2011 .......273Factors that May Restrict Use of Disposables: CMO’s vs.

Biotherapeutic Developers ...............................................................276Most Critical Reasons for Restricting Use of Disposables .....................279Most Important Reasons for Not Increasing Use of

Disposables, 2008-2011 ..................................................................280Most Important Reasons for Restricting Use of Disposables:

Biotherapeutic Developer vs.CMO ..................................................282Top Reasons for Not Increasing the Use of Disposables: US vs.

European Respondents ....................................................................284

8-4 Standards Setting for Disposable, Single-use Systems .......................287Design and Engineering Standards Settings .........................................287Leachables and Extractables Standards Settings .................................288Component Manufacturing Control (Quality) Standards Settings ..........289Organizations from Which End Users Expect Standards Settings ........290

8-5 Current Budgets for Disposable Systems ..............................................294Budgets for Disposable Systems, 2007-2011 ........................................296Annual Growth Rate in Budgets for Single-use Components 2007-2011 298Data Findings, CAGR ............................................................................298Current Budget for Disposables: CMO’s vs.

Biotherapeutic Developers ...............................................................301

©2011 BIOPLAN ASSOCIATES, INC. • NO UNAUTHORIZED REPRODUCTION PERMITTED • ALL RIGHTS RESERVED xvii

TABLE OF CONTENTS

8-7 Disposable Bioreactor Attributes ............................................................304Waste Disposal of Single-use Devices (2010 Data) ..............................307Comments in 2010 regarding Waste Disposal Issues: ..........................307Comments in 2009 regarding Waste Disposal Issues: ..........................308

8-8 Satisfaction with Vendors of Disposables for Biopharmaceutical Manufacturing ..........................................................311

8-9 Discussion ................................................................................................314The Expanding Use of Single-use Devices ............................................314Current Markets .....................................................................................314Safety Concerns with Disposables ........................................................315Summary ................................................................................................315

CHAPTER 9: Downstream Purifi cation .........................................3239-1 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 Specifi c Purifi cation Step Constraints....................................................332Changes in Impact on Capacity of Purifi cation Steps, 2008-2011 .........333Specifi c Purifi cation Step Constraints, US vs. Western European

Biomanufacturers .............................................................................334

9-3 Downstream Purifi cation Issues Facing the Industry Today ...............336Protein A and Alternatives ......................................................................336Changes in Perception of Protein A and Alternatives .............................337Protein A Downstream Purifi cation Issues, US vs Western Europe .......339

9-4 Problems in Downstream Purifi cation ....................................................340

9-5 New Downstream Processing Technologies ..........................................343New Downstream Processing Solutions; 2010 – 2011 ..........................345New Downstream Processing Technologies; Biotherapeutic

Developers vs. CMOs ......................................................................346New Downstream Processing Technologies; US vs Western Europe ...348

9-6 Improvements to Downstream Operations.............................................350Comparison of New Downstream Technology Investigations;

Biomanufacturers vs CMOs .............................................................351Comparison 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 Biopharmaceutical Manufacturing .............................................357

Introduction ............................................................................................357

10-1 Process Analytical Technology(2010 Data) ..........................................358PAT 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 ..................................................................377Comparison of Implementation Plans 2009 - 2011 ................................378

10-7 Quality Initiative Implementation...........................................................381Comparison of Quality Initiative Implementation, 2009 - 2011 ...............383

10-9 Global Quality Supply Management ......................................................385Global Quality Supply Management ......................................................386US vs W. European Global Quality Supply Management ......................388

10-10 Effect Of Cost-Cutting on Overall Quality Operations .....................392CMOs Impact of Cost Cutting on Quality Manufacturing .......................393US vs Western European Impact of Cost Cutting on

Quality Manufacturing ......................................................................395

10-11 Discussion ............................................................................................396

CHAPTER 11: Hiring, Employment Growth, and Training in Biopharmaceutical Manufacturing .............................................397

Introduction ............................................................................................397

11-1 Hiring in 2011 ...........................................................................................398

11-2 Hiring in 2015 ...........................................................................................399

11-3 Hiring Challenges Today .........................................................................401Hiring Diffi culties; 2010 vs 2011 .............................................................403Hiring Diffi culties: US vs Western Europe ..............................................406

11-4 Training in Biopharmaceutical Manufacturing .....................................409Changes 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 ..........................................................................................415Areas of Involvement .............................................................................415Location of Vendor Sales ......................................................................418Respondents’ Primary Job ....................................................................420

12-2 Growth Rate of Sales by Suppliers .......................................................421Average Industry Growth Rate, Distribution ...........................................421Average Industry Growth Rate, By Segment .........................................424Vendor Sales Growth Rate, by Industry Segment, 2007 to 2011 ...........425Overall Vendor Sales Growth, 2007-2011 ..............................................427Vendor Annual Sales, Distribution ..........................................................429

12-3 Discussion: Industry Growth Rates ......................................................430

12-4 Budget Issues and Problems Faced by Industry Supplier...................431Budget Challenges in 2011 ....................................................................431Vendor Average Budget Changes for 2009 -2011..................................433Vendor Pricing Changes ........................................................................434Future Price Changes for 2012 ..............................................................435CMO Price Changes .............................................................................437Average CMO Pricing Shift, 2010-2011 .................................................439

12-5 Cost Cutting Actions by Vendors ...........................................................441Cost Cutting Actions, By Segment .........................................................442

12-6 Problems Faced by Vendors ...................................................................443Problems Faced by Vendors’ Clients .....................................................444Vendor Expansion Plans for 2011 ..........................................................446Biopharma Vendor Business Trends, 2010 vs 2011 ..............................448Top New Technology Areas in Development by Vendors .......................449Other NPD activities: ..............................................................................451

12-6 Discussion: Supplier Issues .................................................................453

12-7 Sales Staff Training .................................................................................455Days of Training Provided .....................................................................455Areas where Training May Help Sales Staff Perform .............................456Areas 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 T A B L E S :Fig 1.1: FDA Approvals of New Biopharmaceutical Products 1982-2010 ................ 2Fig 1.2: Investigational Drugs: Large Molecule (Protein Therapeutics),

Worldwide, March 2011 vs March 2010 ...................................................... 4Fig 1.3: Current Worldwide Pipeline & Launched Products,

Large Molecules, March 2011 ..................................................................... 8Fig 2.1: Area of Involvement in Biopharmaceutical Manufacturing ........................ 24Fig 2.2: Area of Involvement in Biopharmaceutical Manufacturing, 2010 vs 2011 25Fig 2.3: Respondents’ Job Responsibilities ............................................................ 26Fig 2.4: Facility Location ......................................................................................... 27Fig 2.5: Facility Location, by Region ....................................................................... 28Fig 2.6: Biopharmaceutical Manufacturing Systems, (2007-2011) Trends............. 29Fig 2.7: Phase of Development of Surveyed Respondents ................................... 30Fig 2.8: Distribution of Employees at Facility, and Organization ............................ 31Fig 2.9: Distribution of Total Batches Run at Facility Last Year,

by Scale of Production ............................................................................... 33Fig 3.1: Biomanufacturers’ Budget Shifts for 2011 ................................................. 36Fig 3.2: Approximate Average Change in Biomanufacturers’ Budgets for 2011 ... 37Fig 3.3: Approximate Average Change in Biomanufacturers’ Budgets for 2011 ... 39Fig 3.4: Operational Changes Due to Recent Global Economics .......................... 42Fig 3.5: Operational Changes Due to Recent Global Economics, 2011 vs 2010 ... 43Fig 3.6: Operational Changes Due to Recent Global Economics;

Biotherapeutic developers vs CMO’s ........................................................ 45Fig 3.7: Operational Changes Due to Recent Global Economics;

US vs Western Europe ............................................................................... 47Fig 3.8: New Product Development Focus Areas ................................................... 52Fig 3.9: New Product Development Focus Areas, 2011 vs 2010 ........................... 55Fig 3.10: New Product Development Areas of Interest:

Biotherapeutic Developers vs CMO’s ........................................................ 57Fig 3.11: New Product Development Areas of Interest:

US vs Western Europe and ROW .............................................................. 59Fig 3.12: Factors in Biomanufacturing Performance Creating “Signifi cant”

or “Some” Improvements ........................................................................... 61Fig 3.13: Factors in Biomanufacturing Performance Creating “Signifi cant”

or “Some” Improvements: 2011 vs 2010 ................................................... 63Fig 3.14: Factors in Biomanufacturing Performance Creating “Signifi cant”

or “Some” Improvements: Biomanufacturers Vs CMOs ............................ 67Fig 3.15: Factors in Biomanufacturing Performance Creating “Signifi cant”

or “Some” Improvements: US Vs Western Europe Vs Rest of World ......... 69Fig 3.16: Cost-Cutting Changes: Actions Undertaken During Past 12 Months ........ 71Fig 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 ............... 73Fig 3.19: Activities Implemented to Speed Drug Development Timelines;

Biomanufacturers vs CMOs ....................................................................... 75Fig 3.20: Biomanufacturing Assay ‘Areas’ Urgently Requiring New,

Improved Testing Methods ........................................................................ 76Fig 3.21: Biomanufacturing Assay ‘Areas’ Urgently Requiring New,

Improved Testing Methods; Biomanufacturers vs CMOs .......................... 77Fig 3.22: Biomanufacturing Assay ‘Areas’ Urgently Requiring New,

Improved Testing Methods; US vs Western Europe .................................. 79Fig 3.23: Perfusion Operations Issues: Perfusion vs Batch-Fed

Processes (Note: 2010 Data) ..................................................................... 81Fig 4.1: Capacity Utilization, By System, 2011 ....................................................... 89Fig 4.2: Capacity Utilization, By System, 2004-2011 ............................................. 92Fig 4.3: Change in Capacity Utilization, CAGR, 2006-2011 ................................... 94Fig 4.4: Capacity Utilization, By System, Biotherapeutic Developer vs CMOs ...... 96Fig 4.5: Capacity Utilization By System, US vs. Western Europe ........................... 98Fig 4.6: Current Production Capacity Distribution, Mammalian Cell Culture ........ 101Fig 4.7: Estimated Bioreactor Capacity Distribution, by Biotherapeutic

Developer (2006 vs 2010) ....................................................................... 105Fig 4.8: Estimated Bioreactor Capacity Distribution, by Contract Manufacturing

Organizations (CMO), 2006, vs 2010, vs 2011 ........................................ 106Fig 4.9: Current Production Capacity Distribution, Microbial Fermentation ......... 107Fig 4.10: Current Production Capacity Distribution, Yeast ..................................... 108Fig 4.11: Current Production Capacity Distribution, Insect Cells ........................... 109Fig 4.12: Mammalian Cell Culture Capacity Estimates 2003-2011 ........................ 111Fig 4.13: Microbial Fermentation Capacity Estimates 2003-2011 .......................... 111Fig 4.14: Range of Titres for Mabs Obtained at Various Production

Scales, Distribution .................................................................................. 115Fig 4.15: Annual Average Mab Titre Increase, 2008-2011 ..................................... 116Fig 5.1: Capacity Constraints, by Stage of Production ......................................... 122Fig 5.2: Capacity Constraints, 2004 through 2011 ............................................... 125Fig 5.3: Capacity Constraints Trends, 2004-2011 ................................................ 126Fig 5.4: Capacity Constraints, Biotherapeutic Developers vs CMOs ................... 127Fig 5.5: Capacity Constraints, US vs. Europe ...................................................... 130Fig 5.6: Expectations of Capacity Constraints; by Stage of Production;

fi ve-year Projections ................................................................................ 132Fig 5.7: Expectations of Capacity Constraints: Five-year Projections

Made in 2004-2011 .................................................................................. 135Fig 5.8: Expectations of Capacity Constraints: Five-year Projections

Made in 2004-2011 (Trend Line) .............................................................. 136Fig 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.. 139Fig 5.11: Factors Creating Future Capacity Constraints ........................................ 141FIG 5.12: Factors Creating Future Capacity Constraints, 2008-2011 ..................... 144Fig 5.13: Factors Creating Future Capacity Constraints, CMOs vs

Biotherapeutic Developers ..................................................................... 147Fig 5.14: Factors Creating Future Capacity Constraints, US vs Western

European Biomanufacturers .................................................................... 152Fig 5.15: Key Areas to Address to Avoid Capacity Constraints ............................ 154Fig 5.16: Key areas to Address to Avoid Capacity Constraints; 2006-2011 .......... 156Fig 5.17: Key areas to Address to Avoid Capacity Constraints;

Biomanufacturers vs CMOs ..................................................................... 160Fig 5.18: Key areas to Address to Avoid Capacity Constraints;

U.S. vs Western Europe ........................................................................... 163Fig 6.1: Industry Average Planned Production Increase by 2015 ........................ 170Fig 6.2: Planned Future Capacity Expansion: 5-year Estimates,

2009 through 2015 ................................................................................... 171Fig 6.3: Planned Future Capacity Expansion: 5-year Estimates,

2009 - 2015 (Trend Line) .......................................................................... 172Fig 6.4: Planned Future Capacity Expansion: 5-year Estimates;

Biotherapeutic Developers vs CMOs ...................................................... 175Fig 6.5: Planned Future Capacity Expansion: 5-year Estimates, 2009 - 2015,

US vs Western Europe ............................................................................. 177Fig 6.6: Percent of Respondents Projecting Production Increases of

over 100% by 2015; 4-year Trend ............................................................ 179Fig 7.1: Current Percent Production Outsourced; by System, 2009 ..................... 188Fig 7.2: Biopharmaceutical Manufacturing Facilities Outsourcing

NO Production, 2006-2011 ...................................................................... 190Fig 7.3: Biopharmaceutical Manufacturing Facilities Outsourcing

NO Production, 2006-2011 (Trend Line ................................................... 191Fig 7.4: Future Outsourcing: Percent Production Outsourced;

by System, in 2015 .................................................................................. 193Fig 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 ‘Signifi cantly Higher Levels’ in 2 Years ..................................................................................... 203

Fig 7.9: Outsourcing Activities Projected to be Done at ‘Signifi cantly 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 ......................... 247Fig 8.4: 6-Year Percentage-Point Change in First-Usage of

Disposables, 2006-2011 .......................................................................... 248Fig 8.5: Usage of Disposables in Biopharmaceutical manufacturing, by

Stage of Manufacture (R&D through Commercial Manufacture) ............ 251Fig 8.6: Newly Introduced Disposables, Past 12 Months ..................................... 253Fig 8.7: Current Issues: Leachables and Extractables in Disposable Devices .... 257Fig 8.8: Usage of Disposables in Biopharmaceutical Manufacturing;

Biotherapeutic Developer vs CMO .......................................................... 259Fig 8.9: Reasons for Increasing Use of Disposable System

Components in 2011 ................................................................................ 262Fig 8.10: Reasons for Increasing Use of Disposables 2006-2011 ......................... 264Fig 8.11: Reasons for Increasing Use of Disposable System Components,

Biotherapeutic Developers vs CMOs ...................................................... 267Fig 8.12: Most Critical Reason for Increasing Use of Disposables ........................ 270



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Fig 8.13: Reasons for Restricting Use of Disposables .......................................... 272Fig 8.14: Factors Restricting Use of Disposables, 2006-2011 ............................... 275Fig 8.15: Factors Restricting Use of Disposables in Biotherapeutic

Developer vs CMO .................................................................................. 277Fig 8.16: Top Reasons for Not Increasing Use of Disposables, 2011 .................... 279Fig 8.17: Top Reasons for Not Increasing Use of Disposables, 2008-2011 ........... 281Fig 8.18: Top Reasons for Not Increasing Use of Disposables,

Biotherapeutic Developer vs CMO .......................................................... 283Fig 8.19: Top Reasons for Not Increasing Use of Disposables,

U.S. vs Western Europe ........................................................................... 285Fig 8.20: Standards Setting for Design and Engineering;

Organizations Expected to Set Standards .............................................. 287Fig 8.21: Standards Setting for Design Leachables and Extractables;

Organizations Expected to Set Standards .............................................. 288Fig 8.22: Standards Setting for Component Manufacturing Control (Quality);

Organizations Expected to Set Standards .............................................. 289Fig 8.23: Standards Setting for Component Manufacturing Control (Quality);

Organizations Expected to Set Standards .............................................. 290Fig 8.24: Average Budget Per Facility, Single-use Disposable

System Components ................................................................................ 295Fig 8.25: Average Budget, Single-use Disposable System

Components, 2007 vs 2010 ..................................................................... 297Fig 8.26: CAGR: Growth Rate in Budget on Single-use / Disposable

System Components 2007-2011 (by device) .......................................... 299Fig 8.27: Average Disposables Budget Per Facility, Disposable

Systems; Biotherapeutic Developers vs CMOs ..................................... 302Fig 8.28: Disposable Bioreactor Attributes Considered “Very Important” .............. 305Fig 8.29: Disposable Bioreactor Attributes Considered “Very Important”,

2010 vs 2011 ........................................................................................... 306Fig 8.30: Impact of Waste Disposal for Disposables (Note: 2010 data)................. 309Fig 8.31: Single-Use Product Vendor Satisfaction Factors ..................................... 312Fig 9.1: Impact of Downstream Processing on Overall Capacity ......................... 325Fig 9.2: Impact of Downstream Processing on Overall Capacity;

Biotherapeutic Developers vs CMOs ...................................................... 328Fig 9.3: Impact of Downstream Processing on Overall Capacity;

U.S. vs Western Europe ........................................................................... 330Fig 9.4: Impact on Capacity of Depth, Chromatography and

UF Purifi cation Steps ............................................................................... 332Fig 9.5: Impact on Capacity of Purifi cation Steps: Experiencing at

“Signifi cant” or “Severe” Constraints, 2008 - 2011 .................................. 333Fig 9.6: Impact on Capacity of Purifi cation Steps, U.S., vs Western Europe ....... 334Fig 9.7: Issues Regarding Protein A Usage ......................................................... 336Fig 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 .................. 339Fig 9.10: Problem Areas in Downstream Operations, 2007 vs 2009

(Data from 2010 Study) ........................................................................... 341Fig 9.11: New Downstream Processing Solutions in 2010 ..................................... 344Fig 9.12: New Downstream Processing Solutions; 2010 - 2011 ............................. 345Fig 9.13: New Downstream Processing Solutions in 2010;

Biotherapeutic Dev. vs CMO ................................................................... 347Fig 9.14: New Downstream Processing Solutions in 2011;

US vs. Western Europe ............................................................................ 349Fig 9.15: Improving Downstream Operations ......................................................... 350Fig 9.16: Improving Downstream Operations; Biomanufacturers vs CMOs ........... 351Fig 9.17: Improving Downstream Operations (US Vs Western Europe Vs ROW) ... 352Fig 10.1: Implementation of Process Analytical Technology (PAT) for New

Biomanufacturing Processes, 2009 vs 2010 (2010 Data) ....................... 359Fig 10.2: Hurdles Hindering Implementation of PAT (2008 - 2011) ........................ 362Fig 10.3: Batch Failure Frequency Distribution, 2009 – 2011 ................................. 367Fig 10.4: Average Rates of Failure, by Primary Cause, and Phase of

Manufacture, 2011 ................................................................................... 370Fig 10.5: Average Rates of Failure, by Primary Cause, and Phase of

Manufacturing 2009 - 2011 (Commercial Manufacture) .......................... 371Fig 10.6: Quality problems traced to vendors ........................................................ 374Fig 10.7: Automation Technologies Implemented, or to be Implemented in 2011 . 377Fig 10.8: Automation Technologies to be Implemented; Comparing 2009 - 2011 . 378Fig 10.9: Quality Initiative Implemented Currently, or within Next 12 Months ......... 381Fig 10.10: Quality Initiative to be Implemented in “Next 12 Months”,

Comparing 2009 - 2011 ........................................................................... 383Fig 10.11: Global Quality Supply Management ........................................................ 385Fig 10.12: Global Quality Supply Management (Biomanufacturers vs CMOs) ........ 387Fig 10.13: Global Quality Supply Management (US vs W. Europe).......................... 389Fig 10.14: Cost Cutting Impact on Quality ................................................................ 392Fig 10.15: Cost Cutting Impact on Quality (Biomanufacturers Vs CMOs) ................ 394Fig 10.16: Cost Cutting Impact on Quality (US vs Western Europe) ........................ 395Fig 11.1: New Hires in Biopharmaceutical Manufacturing (2011) .......................... 398Fig 11.2: New Hires in Biopharmaceutical Manufacturing (2015) .......................... 399Fig 11.3: Areas Where Hiring Diffi culties Exist in Biopharmaceutical Operations .. 402Fig 11.4: Areas Where Hiring Diffi culties Exist in Biopharmaceutical

Operations; 2010 vs 2011 ........................................................................ 404Fig 11.5: Areas Where Hiring Diffi culties Exist in Biopharmaceutical

Operations, US vs. Western Europe ........................................................ 407Fig 11.6: Training for New Operations/Manufacturing Employees ......................... 410Fig 11.7: Changes in Training for New Operations/Manufacturing Employees ...... 411



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Fig 11.8: Global Health Interest .............................................................................. 412Fig 12.1: Area of Biopharmaceutical Involvement, Vendor .................................... 417Fig 12.2: Area of Biopharmaceutical Involvement, Vendors, 2011 vs 2010 ........... 417Fig 12.3: Geographic Locations in which Vendors Currently

Actively Sell Products or Services ........................................................... 418Fig 12.4: Respondents’ Primary Job Function ........................................................ 420Fig 12.5: Biopharmaceutical Supply Market Segment Sales

Growth Distribution .................................................................................. 422Fig 12.6: Average Annual Vendor Segment Sales Growth Rates, 2011 ................. 424Fig 12.7: Average Annual Vendor Sales Growth Rate,

2007 – 2011, by Segment ........................................................................ 425Fig 12.8: Average Annual, Vendor Sales Growth Rate, 2007 – 2011 ..................... 427Fig 12.9: Average Annual Vendor Sales Trend Line, 2007 - 2011, by Segment ..... 428Fig 12.10: Vendors’ Approx Annual Sales to Biopharmaceutical Segment % ......... 429Fig 12.11: Vendors’ Average Budget Change for 2011 ............................................ 431Fig 12.12: Vendors’ Average Budget Change for 2009 - 2011, Summary ............... 433Fig 12.13: Vendors’ Average Pricing Changes in 2011 ............................................ 434Fig 12.14: Vendors’ Average Pricing Changes, 2009 Actual - 2012 Projected ........ 435Fig 12.15: CMOs Service Price Shifts in 2011, Distribution ...................................... 437Fig 12.16: Average CMOs Service Price Shifts in 2010 ........................................... 438Fig 12.17: Average CMOs Service Price Shifts 2010 vs 2011 .................................. 439Fig 12.18: Actions undertaken to reduce overall costs, past 12 months ................. 441Fig 12.19: Actions undertaken to reduce overall costs in past 12 months,

By Segment ............................................................................................. 442Fig 12.20: Problems Faced by All Suppliers ........................................................... 443Fig 12.21 (Fig 10.6 Recap): Biomanufacturers’ and CMOs Quality

Problems Traced to Vendors .................................................................... 444Fig 12.22: Biopharma Business and Marketing Plans, 2011 .................................... 446Fig 12.23: Biopharma Business and Marketing Plans, 2010 vs 2011 ...................... 448FIG 12.24: Top New Technologies or New Product Development Areas .................. 450Fig 12.25: Days of Sales Staff Training Provided ...................................................... 455FIG 12.26: Areas Where Training May Help Sales Staff Perform Better;

All Respondents vs Sales Reps Only ...................................................... 456FIG 12.27: Areas Where Training May Help Sales Staff Perform

Better; 2010 vs 2011 ................................................................................ 458

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T A B L E STable 1.1: Biologics (Large Molecule), Worldwide, through March 2011 .................... 5Table 1.2: Summary All Therapeutics vs Biologics (Large Molecule),

Worldwide, through March 2011 (Comparing 2008-2010) .......................... 6Table 1.3: Worldwide Pipeline, Large Molecules, 2011 ............................................... 7Table 1.4: Summary of Worldwide Biopharmaceutical Revenue by

Product Class, 2007 and 2010 estimates .................................................. 11Table 1.5: Biopharmaceutical Blockbusters: >$1 billion revenue, and

Expression Systems/Host Cells (2010 vs 2009) ........................................ 12Table 1.6: Biopharmaceutical Markets ñ Products and Revenue by Class ............... 15Table 1.7: Monoclonal Antibody Therapeutic Products Revenue & Approvals.......... 15Table 1.7: Expression Systems/Host Cells for U.S./EU-Marketed

Cultured Biopharmaceuticals .................................................................... 19Table 3.1: Areas of Signifi cant Projected Budget Increases for Biomanufacturing,

Past Three Years: ....................................................................................... 38Table 4.1: Distribution of Mammalian Cell Culture Capacity in 2011,

Product Manufacturers ........................................................................... 104Table 4.2: Distribution of Mammalian Cell Culture Capacity Among Contract

Manufacturing Organizations (CMOs), 2011 data ................................... 106Table 4.3: Compound Annual Change in Mab Titre, 2008-2011 .............................. 117Table 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 ............................................................................ 329Table 10-1: Batch Failures, Average Weeks per Failure, per Facility, 2008-2011 ...... 366Table 12-1: Average Industry Growth Rate, 2007 -2011 ............................................ 421Table 12.2: Top 14 Areas of biopharma R&D and New Product Development .......... 451Table 12-3: Average Vendor Sales and Technical Training Days, 2010 - 2011 .......... 455


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O V E R V I E WMarket Trends

Despite 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 effi ciency, 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 profi ts and profi t margins, and are more diffi cult 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, profi table 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 fi led with FDA in 2011. There are currently about 350 biopharmaceutical products approved in the U.S. This number will grow signifi cantly in coming years, particularly as multiple biosimilar (and bio-better) versions of most every established biopharmaceutical enter the market.

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C H A P T E R 3 :

E M E R G I N G I S S U E S I N

B I O P H A R M A C E U T I C A L

M A N U F A C T U R I N G

3 - 1 B U D G E T I S S U E S I N 2 0 1 1

This 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 scientifi c staff, and new facility construction.

The fi nancing 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 more milestone performance and 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 fi nding vendors’ budgets are also up, aside from new facility construction, by as much as 4%. This is a signifi cant reversal from the past three years (see Chapter 12).

Healthcare segments historically have been relatively insulated from adverse fi nancial 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 scientifi c staff are down this year, operations training to improve effi ciency is up once again, (5.2% this year, compared

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th · 2015. 10. 5. · of Millenniumís biologics pipeline. In this role he pioneered the use of disposable manufacturing systems for the production of monoclonal antibodies and helped