The Impact of Global Product Development: a US FDA Perspective

1
The Impact of Global Product Developmenta US
FDA Perspective

• Murray M. Lumpkin, M.D.
• Deputy Commissioner
• International and Special Programs
• US Food and Drug Administration

2
Time of Radical Change

• Cellular medicine to molecular medicine
• Splitting atoms to splitting genes
• Industrial economies to global economies
• Changes have brought both incredible promise and
  significant challenges

3
Agenda

• Globalisation
• Globalisation of Pharmaceuticals
• Globalisation of Regulation
• Globalisation of Clinical Trials

4
Globalisation

• Global technology makes mass production of
  pharmaceutical products possible, but also makes
  mass production of counterfeit products a reality
  and the growing currency of organised crime.

5
Globalisation

• Global Internet technology makes instantaneous
  communication of important drug safety
  information possible around the world, but also
  facilitates instantaneous access to illicit
  pharmacies that are defrauding consumers and
  that disappear with the push of a delete button
  when a regulator investigates

6
Globalisation

• The global economy supports new scientific
  disciplines that are taking us into the molecular
  world of genetics-based personalised medicine,
  but also fosters a world in which most people
  still die of infections for which we have not yet
  produced simple, effective, available therapies.

7
Globalisation

• Global transport systems facilitate a world
  around which we can travel in ways about which
  our grandparents only dreamed, but also
  facilitates a world in which any microorganism,
  any radiation emitting device, or any
  intentionally contaminated product can be almost
  anywhere in the world in 24 hours.

8
Pharmaceutical Globalisation

• Drug discovery, development, authorisation,
  marketing, and use in geographic isolation simply
  does not exist in the global world of today
• Pharmaceutical products are global commodities
• Pharmaceutical clinical databases are global
  resources

9
Pharmaceutical Globalisation

• Dossiers are global and because regulators talk
  with each other earlier and more often today than
  ever before, companies can no longer choose to
  the same degree when they are being global and
  when they are being local

10
Pharmaceutical Globalisation

• The public messages of companies are global.
  Patients and practitioners in most of the world
  know what companies are doing with their products
  in other parts of the world.
• What they are claiming
• When the products are available
• What the companies are charging
• And there is even more pressure for greater
  transparency

11
Regulatory Globalisation

• Harmonisation Initiatives
• ICH
• VICH
• GHTF

12
Regulatory Globalisation

• Industry wanted regulators to talk to each other
• Numerous confidentiality arrangements
• Clusters
• Instantaneous communications between regulators
• Numerous guidances regarding technical
  requirements
• CGPs

13
Regulatory Harmonisation

• Harmonisation does not equal homogenisation
• Sometimes adaptation of a practice is better than
  adoption of practice
• Blessedly we are not all genetic or cultural
  clones of each other

14
What hasnt harmonised

• Pharmaceutical Laws and legal authorities of
  regulators
• Parliamentary expectations
• Medical Practice
• Cultural expectations including risk tolerance
  and perception of what is meant by benefit
• Product Reimbursement practices
• Liability laws and practices
• Product Promotion practices
• Risk Communication and Risk Mitigation tools
• Dates of MAAs submissions
• Data in MAAs
• Company marketing desires in different markets

15
Globalisation of Clinical Trials

• A growing reality
• Serving multiple purposes and goals
• Has many positive aspects, but, like other
  results of globalisation, has some significant
  challenges

16
Clinical Trials Globalisation

• Catalyst -- Time is money
• Recruitment, enrollment of evaluable patients as
  quickly as possible
• Driving trials to more parts of the world than
  previously seen, especially the so-called
  emerging economies (Eastern Europe, Latin
  America, and Asia)
• Still most data in our MAAs come from
  non-emerging economies.

17
Acceptance of foreign clinical data

• Code of Federal Regulation 312.120
• Code of Federal Regulation 314.106
• Can either be conducted under a US FDA IND or not
  under a US FDA IND
• Investigator Qualifications substantiated
• Research Facilities described
• Study reports as for domestic and records
  accessible for US FDA inspection if needed

18
Acceptance of foreign clinical data

• Ethical standards
• Declaration of Helsinki
• ICH GCP
• Data must be applicable to the US population and
  US medical practice

19
Present Impacts

• CGP inspections in all parts of the world
• Increased resources
• Assessing qualifications
• Increased knowledge of various medical
  qualifications and medical practice legislation
• Increased interactions with counterpart
  regulatory authorities around the world,
  especially if safety issues during clinical
  trials

20
Present Impacts

• Ethical standards, ethics committees, and
  documentation
• How does one define exploitation and does it
  disqualify data individual ethics versus
  population ethics. Are patients the end or a
  means to an end?
• How does one define standard of care and what
  if it is no treatment because therapies are not
  available
• How does one define legitimate consent in many
  social contexts different from ones own
• What is the perspective by which this is judged
  local or reviewing authority
• Especially when we get to the situation where the
  great majority of the data come from areas new to
  the clinical trials arena

21
Present Issues

• Relevance of the treated population in the
  clinical trial to the US population and medical
  practice
• Not a new issue. ICH E5 has grappled with this
  for years. (Is bridging the answer to the
  questions?)
• Comparator products
• Appropriate primary endpoints for desired claims,
  especially as we get into new biomarkers must
  they population validated?
• Underlying illnesses
• Concomitant therapies
• Cultural issues food, dietary supplements,
  herbals

22
Conclusion

• Globalisation of clinical trials is a growing
  reality
• It has many apparent benefits, but also many
  significant challenges from a regulatory
  perspective
• Requires significant discussion with regulatory
  authorities as product being developed
• Companies need to know that these are the types
  of questions that will be asked more and more
  frequently as these data become more prominent
• World is getting flatter and we are becoming more
  and more knowledgeable about each others systems
  and practices and are better able to make
  regulatory decisions for our own jurisdictions
  based on a global clinical trials database.