Biomanufacturing capacity for biosimilars: Is there enough?

Transcription

Biomanufacturing capacity for biosimilars: Is there enough?
Biomanufacturing Capacity for
Biosimilars: Is there enough?
Cambridge Healthtech Institute’s Third Annual
BIOAnalytical Summit
2012 Mar 19-22
Baltimore, MD
BioProcess Technology Consultants
www.bptc.com
Increasing Sales of Biopharmaceutical Products
From Clone to Clinic®
Biologic Products – Current and Future
Ref: Stout, J. BPI Conference 2011
From Clone to Clinic®
What Are Biosimilars?
 Successor to an innovator product for which patent protection no longer applies
 Complex molecules manufactured by recombinant DNA technology
 Comparable with the innovator product in terms of quality, efficacy, and safety
EU draft general guidelines adopted 2004
First biosimilar somatropin
approved and launched in EU
2005
Somatropin ‐ first biosimilar approved worldwide (Australia)
2006
First biosimilar EPO approved and launched in EU
2007
First biosimilar filgrastim approved and launched in EU
2008
2010
2009
Japan regulatory guidelines
US regulatory pathway
First biosimilar somatropin approved and launched in Japan & Canada
From Clone to Clinic®
Biosimilars Are Reality and Growing…
 Today relatively simple proteins ‐‐ tomorrow, more complex proteins
 Biosimilar products currently approved in Europe
Product Name
Abseamed
Binocrit
Epoetin alfa Hexal
Biograstim
Filgrastim Hexal
Filgrastim Ratiopharm
Nivestim
Ratiograstim
Tevagrastim
Zarzio
Omnitrope
Valtropin
Retacrit
Silapo
Active Substance
Epoetin alfa
Filgrastim
Somatropin
Epoetin zeta
Ref: http://www.gabionline.net/Biosimilars/
General/Biosimilars‐approved‐in‐Europe Company
Medice Arzneimittel Pütter Sandoz
Hexal
CT Arzneimittel
Hexal
Ratiopharm
Hospira
Ratiopharm
Teva Generics
Sandoz
Sandoz
BioPartners
Hospira
Stada
From Clone to Clinic®
Adoption Rates of Biosimilars in Europe
Biosimilar Share of Innovator Product Sales (March 2011)
Country
Somatropin (1)
Erythropoietin (5) Filgrastim (6)
Austria
6%
50%
52%
France
20%
11%
42%
Germany
12%
65%
45%
Greece
N/A
67%
53%
Italy
12%
7%
18%
Poland
7%
62%
38%
Romania
34%
58%
77%
Spain
15%
16%
24%
Sweden
21%
63%
45%
UK
4%
9%
80%
EU Total
13%
18%
38%
6
From Clone to Clinic®
Biosimilar Development Is Lengthy And Expensive
Generics*
US$ 2 – 3m
Biosimilars*
US$ 100 - 150m
Innovator*
US$ 800m
Development
Investment
2 – 3 yrs
7 – 8 yrs
8 – 10 yrs
Time to market
20 – 50 pts
~ 500 pts
800 – 1000 pts
# of patients for
approval
*Industry average
Ref: Visser, J. BPI Europe 2010
From Clone to Clinic®
Monoclonal Antibodies Will Be The Next Wave
 Many blockbuster MAbs will be off patent in the next few years
•
Biosimilar MAbs already available in India and China
 Monoclonal antibody products soon to be off patent:
Product Name
Active Substance
Company
Avastin
Bevacizumab
Roche/Genentech
Enbrel
Etanercept
Amgen
Erbitux Cetuximab
Eli Lilly
Herceptin
Trastuzumab
Roche/Genentech
Humira
Adalimumab
Abbott
Lucentis
Ranibizumab
Roche/Genentech
Remicade
Infliximab
Johnson & Johnson
Rituxan
Rituximab
Roche/Genentech
Ref: http://www.gabionline.net/Reports/Top‐25‐biotech‐
drugs‐the‐next‐biosimilars‐targets
From Clone to Clinic®
Product Demand Greatest for Monoclonal Antibodies
Demand for existing commercial antibody products will nearly double by 2016
 ~8.3 metric ton  ~13.4 metric tons
(2010)
Product Demand for Commercial Antibody Products
(2016)
 2010 requirements for each of the top five monoclonal antibody products ranged from 1.0 – 2.3 metric ton
All others
(27)
26%
Remicade
17%
 2010 demand for all other monoclonal antibody products combined was approximately 2.5 metric tons
 Anticipated demand for new monoclonal antibody products approved between now and 2016 is expected to be
<5 metric tons/year/MAb
Avastin
16%
Herceptin
12%
Enbrel
13%
Rituxan
16%
From Clone to Clinic®
Demand for Biomanufacturing Capacity Growing
 Driven by growing market for approved products, large number of products in clinical development, and growing interest in biosimilars
 Volumetric requirements will almost double by 2016, leaving companies and markets without capacity scrambling for resources
From Clone to Clinic®
Distribution of Mammalian Cell Culture Capacity
From Clone to Clinic®
Geographic Distribution of Cell Culture Capacity
Perfusion capacity adjusted to equivalent fed‐batch capacity where appropriate
From Clone to Clinic®
Balance of Supply and Demand
Assumes no increase in current titers
Perfusion capacity adjusted to equivalent fed‐batch capacity where appropriate
From Clone to Clinic®
Product Companies Control ~70% of Capacity
4,500
Installed Capacity
3,600
2,700
1,800
900
0
2010
2011
CMO
2012
2013
XS
2014
2015
2016
Product Co.
Perfusion capacity adjusted to equivalent fed‐batch capacity where appropriate
From Clone to Clinic®
Ten Companies Control >75% of Capacity
2010 Volume
(1,000s L)
2016 Volume
(1,000s L)
Roche
525
600
4
J&J
230
230
3
5
Boehringer Ingelheim
216
216
4
6
Amgen
198
198
5
3
Lonza
150
232
6
8
Pfizer
139
149
7
2
Sanofi‐Aventis
133
263
8
‐
Novartis
125
‐
9
10
Lilly
122
137
10
7
Biogen Idec
106
196
‐
9
Celltrion
‐
140
All Others
614
1,070
2010
Rank
2016
Rank
1
1
2
Company
Perfusion capacity adjusted to equivalent fed‐batch capacity where appropriate
From Clone to Clinic®
Capacity Distribution by Bioreactor Scale
From Clone to Clinic®
Source of Uncertainty When Developing a Mfg Strategy
17
From Clone to Clinic®
Drivers for Build, Buy, Acquire Decision
 Core Competency Assessment
•
•
We’re Good At It
Not Many Others Are
 Is “Buy” an Option?
• Technology Requirements
• Scale
• Capacity Availability – Supply vs. Demand
 Strategic Fit •
•
•
Pipeline
Competitive Advantage
Development Stage
 Risk Management
• Control
• Cost and Probability of Failure  Financial Considerations
• Return on Capital
• Cost of Capital
• Operating Costs
From Clone to Clinic®
Product Lifecycle Drives Make vs. Buy Decisions
Make
Buy
Make or Buy
Product Launch
Product Launch
Maturity
Product Life Cycle
Maximizing Control
•
•
Manufacturing costs
set at decision point
RISK
RISK
Manufacturing costs
set at decision point
Development
Market
Uncertainty Uncertainty
Buy or Make
Development
Uncertainty
Market
Uncertainty
Maturity
Product Life Cycle
Conserving Capital
“Make” strategy during highest risk period to maximize control of supply
• “Buy” strategy during highest risk “Buy” strategy may make sense once product lifecycle stabilizes, risk decreases, and control less important
• “Make” strategy may be attractive period to conserve capital
once product lifecycle stabilizes, capital becomes more available, and risk reduced
From Clone to Clinic®
Biopharmaceutical Industry Moving to Outsourcing
 CMO’s are a long‐term sustainable strategy
•
Many large pharmaceutical companies are moving away from internal manufacturing and relying on CMO’s
•
Outsourcing to an experienced CMO presents a faster, more economical approach to market entry  Strategic outsourcing improves flexibility and minimizes capital outlays allowing
•
•
Access to new or different technology as well as expertise and experience
Reduces development time and provides maximum flexibility during development
 Risk mitigation and financial flexibility
•
•
•
Maintain low overhead and minimize cash flow
Minimizes company infrastructure
Eliminates capital investment in manufacturing assets
From Clone to Clinic®
Advantages to Outsourcing
 The vast and complicated development activities required for biologics are often best outsourced, including
•
•
•
Cell line construction, banking, and characterization
Process development, formulation development, analytical methods development
GMP manufacturing
Product availability
Capital Investment Required
Technology transfer/
process development
Cost per lot
Company commitment (FTE)
Risk of process failure
In‐House
CMO
24 – 30 months
18 – 24 months
$10+ Million
<$1 Million
$1 – 2.5 Million
$1.5 – 3 Million
$1 – 5 Million
$1 – 5 Million
20 – 30
3 – 4
Company
CMO/Company
From Clone to Clinic®
Trends in Biomanufacturing – Facilities of the Future

Designed for modern, state‐of‐the art processes
• Cell culture titers of titer >5 g/L
• Smaller bioreactors will produce similar quantities to today’s “six pack” facilities
• Multi‐product capabilities and flexibility will become increasingly important

Expanded use of new technologies to reduce capital investment, increase flexibility, and compress timelines
• Disposable technologies will become increasingly prevalent
• Continuous processing, PAT and other modern manufacturing methods will be incorporated into bioprocessing
From Clone to Clinic®
Thank You!
Patricia Seymour
[email protected]
1.617.417.9240
BioProcess Technology Consultants, Inc.
12 Gill Street, Suite 5450
Woburn, MA 01801
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