Professional Documents
Culture Documents
associates, inc.
April 2011
ISBN 978-1-934106-21-1
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)
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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
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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.
BioPlan Associates, Inc.
2275 Research Blvd., Suite 500
Rockville, MD 20850 USA
www.bioplanassociates.com
Tel: 301-921-5979
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Report and Survey of Biopharmaceutical Manufacturing Capacity and Production
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.
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AUTHORS
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AUTHORS
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.
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Report and Survey of Biopharmaceutical Manufacturing Capacity and Production
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8th Annual Report and Survey of
Biopharmaceutical Manufacturing
Capacity and Production • April 2011
A Study of Biotherapeutic Developers and Contract
Manufacturing Organizations
CONTENTS
Overview ........................................................................... xxix
Market Trends ........................................................................................xxix
Market Potential ...................................................................................xxxiv
Methodology..................................................................... xxxvii
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TABLE OF CONTENTS
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TABLE OF CONTENTS
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TABLE OF CONTENTS
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TABLE OF CONTENTS / FIGURES AND TABLES
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Report and Survey of Biopharmaceutical Manufacturing Capacity and Production
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
Fig 3.13: Factors in Biomanufacturing Performance Creating “Significant”
or “Some” Improvements: 2011 vs 2010 ................................................... 63
Fig 3.14: Factors in Biomanufacturing Performance Creating “Significant”
or “Some” Improvements: Biomanufacturers Vs CMOs ............................ 67
Fig 3.15: Factors in Biomanufacturing Performance Creating “Significant”
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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TABLE OF CONTENTS / FIGURES AND TABLES
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Report and Survey of Biopharmaceutical Manufacturing Capacity and Production
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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TABLE OF CONTENTS / FIGURES AND TABLES
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TABLE OF CONTENTS / FIGURES AND TABLES
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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TABLE OF CONTENTS / FIGURES AND TABLES
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
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C H A P T E R 3:
EMERGING ISSUES IN
BIOPHARMACEUTICAL
M A N U FA C T U R I N G
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
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