the impact of global product development:

The Impact of Global The Impact of Global Product Development:Product Development:a US FDA Perspective a US FDA Perspective

Murray M. Lumpkin, M.D.

Deputy Commissioner

International and Special Programs

US Food and Drug Administration

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Time of Radical ChangeTime 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

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AgendaAgenda

• Globalisation

• Globalisation of Pharmaceuticals

• Globalisation of Regulation

• Globalisation of Clinical Trials

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GlobalisationGlobalisation

• 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.

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GlobalisationGlobalisation

• 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

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GlobalisationGlobalisation

• 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.

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GlobalisationGlobalisation

• 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.

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Pharmaceutical GlobalisationPharmaceutical 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

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Pharmaceutical GlobalisationPharmaceutical 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”

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Pharmaceutical GlobalisationPharmaceutical 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

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Regulatory GlobalisationRegulatory Globalisation

• Harmonisation Initiatives

– ICH

– VICH

– GHTF

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Regulatory GlobalisationRegulatory Globalisation

• Industry wanted regulators to talk to each other– Numerous confidentiality arrangements– Clusters– Instantaneous communications between

regulators

• Numerous guidances regarding technical requirements

• CGPs

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Regulatory HarmonisationRegulatory 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

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What hasn’t harmonisedWhat hasn’t 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

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Globalisation of Clinical TrialsGlobalisation 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

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Clinical Trials GlobalisationClinical 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.

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Acceptance of foreign clinical dataAcceptance 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

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Acceptance of foreign clinical dataAcceptance of foreign clinical data

• Ethical standards – Declaration of Helsinki – ICH GCP

• Data must be applicable to the US population and US medical practice

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Present ImpactsPresent 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

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Present ImpactsPresent 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 one’s 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

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Present IssuesPresent 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

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ConclusionConclusion

• 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 other’s systems and practices and are better able to make regulatory decisions for our own jurisdictions based on a global clinical trials database.