CMO??????????

1
CMO??????????
2
???????

• ??????????????????????????????????,??????????????
  ?
• ?????? (Contract Manufacture Organization)???????/
  ???????,??????????????????????????????????????????
  ??????????(??????)????????

3
????(CMO)?????

• ????? 1980 ????????????,????????????,????????????
  ???????
• ???????????,??????????????,??????????,???????????
  ?,??????????????,??????????

4
????(CMO)?????

• ??/????????????
• ??????,
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• ?????????,??????????,??????
• ????/????

5
??CMO?????

• ??
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• ??/??
• ?????????????45???
• ??????/????

6
??CMO?????

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• ??????????
• ????????,????
• ??
• ??????????????,
• ????????????????
• ???????????

7
????????

• ????,????????????300?????,??????11??????????
• ????????????25??30?,???????30??50?

8
????(CMO)????

• ????????/???????????????7080?,???20??????60??
• ????????????,?????????????(??????????????????????
  ??)???
• ?????????????????/????????

9
????(CMO)????

• ??????????????2000??10 ???,???2005 ?????28
  ???,??20?????????
• ??????????
• ??????????????????????????
• ???????????,????????
• ???????????????,??????????????????

10
CMO???????????
11
CMO??????

• ? ?????
• ? ???????
• ? ????????????

• ? ???????????/????
• ????????,????????????

12
??????

• ?????CMO?
• ???CMO????????!

13
??CMO??

• ?1997??????????????? ? ?
• ? ? ? ? ? ? ? ? ? ????????
• ? ?????????????

14
?????CMO???

• 2000???Tanox(????)????140?,????????????????????
• ?? ??????????(TBMC)

?????,?2002?????
15
lt????gt ,2003
16
????????????

• ????FDA??????????
• 2002????????????
• ???Theravance??????????????

17
??????????????

• ? ?????????????????
• ? ????????????
• ? ??????????

18
???????????

• ?2000???PE Biosystems???????????(primer)???
• ????????,?????????????????

19
??????????????

• ?????CMO??
• ????????????????????????
• ???????????,?????

20
?????????
21
??CMO????

• ?????????????
• ???????????,?????????
• ???????????????

22
??

• The biotech market today and the capacity
  crunch
• Why outsource and factors in choosing a CMO
• Sound process development
• Increasing regulatory requirements

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Capacity crunch
We estimate that demand for manufacturing
capacity will exceed current capacity by a factor
of four by 2005 J. P. Morgan. The State of
Biologics Manufacturing, 2001

• ...the expected needs for increased capacity
  would be almost fourfold for fermentation and
  monoclonal antibodies and ten fold for mammalian
  cell culture. Given that Contract
  biomanufacturers only have an increase of one to
  two fold planned, this shortfall in capacity
  could become significantly painful
• High Tech Business Decisions, 2001

24
Capacity crunch today and tomorrow

• Is the crunch as crunchy today?
• A significant increase in demand for additional
  capacity when new products go into clinical
  trials and market
• Avastin (genentech) and Erbitux (imclone/bms)
  will have impact on capacity
• The crunch depends very much on success of
  products in the clinical trials and improvements
  in yields
• The crunch may not be evenly spread but will most
  likely remain
• scarcity re competent specialists with PRACTICAL
  experience
• Scarcity re capacity at small scale

UBS assumptions Runs per year practically
constant Protein expression level 0.5 (2003), 0.6
(2004), 0.75 (2005), 0.95(2006), Recovery yield
35 (2003), 38 (2004), 40 (2005), 45 (2006),
Probability of success 80 throughout
UBS 2003
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Solutions for meeting capacity demands

• Long term
• Expanding capacity or building new facilities
• Short term
• Improving process development
• Increasing staff and adding shifts
• Develop better expression systems, optimize media
  selection, simplify purification, improve
  processes and technologies

26
??

• ????,????
• ??CRO????!
• ??CMO???????!

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Sound Process Development - the parallel track
Pre clinical Phase I batch
Phase II batch Phase III batch
Tox batch

Manufacturing
Timeline
Minimal process development Focus on few critical
parameters Focus on in-process controls and
analytical methods Focus on impurity profile and
impurity characterization
A
Extensive process development Optimization and
justification of all parameters and extensive
work on critical parameters Focus on yield,
stability, reproducibility and scalability
Reducing number of in-process control and spec.
analyses
B
Process A Discovery processLots of steps Low
yield Low purity Low stability
Process B Manufacturing processFewer steps Good
yield High purity Good stability
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To build or not to build

• Investment of 200-500 million for new
  commercial facility
• 3-6 years completion from design to on-stream
• In the end time and money is more than budgeted
• Need to employ gtmany competent employees as
  biomanufacturing is complex
• Easier access to capacity through partnering
  between haves and haves-not
• Agonist (small quantities) vs. antagonists (large
  quantities) considerations
• Timeline
• Too early? What if candidate fails in CTs
• Too late? Lack of revenue stream

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THINK PRODUCTION SCALE FROM EARLY
DEVELOPMENT Consider environmental, safety and
economical issues Use well established techniques
easy to explain toauthorities (and the buyer
of the process) Design for low bio burden
(Selection of buffers and CIP) Availability of
raw material in large quantities Include
production of stabile intermediate
product Cleanability of equipment The validation
task in production scale
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• Contract Manufacturing Organization (CMO)
• Provider of mammalian and microbial based
  contract services including development and
  manufacture
• Cloning transfection
• Fermentation/Cultivation
• Recovery
• Purification and API formulation
• Analytical development and QC
• Quality Assurance and Regulatory Support
• State-of-the-art new facility designed and
  constructed from green-field for flexible CMO
  services

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Choosing a CMO

• Focus on
• Time, money and competence
• Drawback
• Loss of control of the manufacturing process, is
  the quality level OK?, IP exclusivity
• Dependent on the CMO for your success better
  choose wisely (quality, science, ease of scope
  changes, avoidance of mouse-trapping).
• Benefits
• Lack of in-house capacity
• Avoid capital risk to build facility postpone
  investment
• Reduction of overhead costs, economy of scale
• Access to CMOs capacity, expertise (toolbox),
  experience and flexibility saving internal
  resources for other activites
• CMO typically masters many different technologies
  cost-efficiently
• Complex biotech processes avoid the learning
  curve and how to deal with regulatory bodies
• Established companies
• Leveraging bottlenecks in capacity for
  development and manufacturing and acces to new
  technologies
• Newly established biotech
• Lack of technology, CGMP and regulatory
  competencies and/or financial muscle for
  financing own factory

32

• ???CMO?CRO?????????!
• ??CMO???????
• ????
• ???cGMP????????(CMO)?????(???? )
• ??
• ???? (Bioreactor)
• ??
• ????
• ??

33
CMO?CRO???
34
Why CMO?

• ?????
• ??????????????
• ????

35
Why CRO?

• ????????
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• ????????

36
CMO CRO ??
CMO CRO
?? ??156??? (1998) ????7080? ??110??? (2002) ????600??
?? ???2-3?? (??91?) ???8? (??91?)
37
CMO?SWOT

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38

• ??
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39

• ??
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40

• ??
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CRO?SWOT

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42

• ??
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43

• ??
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• ???????????????,?
• ? CRO ?????

44

• ??
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45

• ???????-
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• ?????? IT ????,?????????
• ??,CMO ? CRO ????????????
• ??????????????,??????
• ?????????,???????????
• ??????

46
CMO? or CRO?