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GOOD MORNING!

BONJOUR!

GOEDEMORGEN!

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An Introduction to certain aspects of the US FDA

Murray M. Lumpkin, MDDeputy Commissioner

International ProgramsUS Food and Drug Administration

Belgian Trade DelegationWashington28 June 2011

3http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm259848.htm

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http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/06/WC500107900.pdf

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FDA – Belgium - Europe

Long history of interactionsConfidentiality arrangements with:

Belgian Scientific Institute of Public Health Belgian Federal Agency for Medicines and Health Products Quality of Medicines & HealthCare (EDQM)Health and Consumer Protection Directorate-General (DG SANCO) EMA EFSA

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Confidentiality Arrangements

Legal Framework to share:Commercial confidential informationPre-decisional informationInvestigative – compliance informationPharmacovigilance data, reportsNOT Trade Secret information

NO requirement to exchange anything

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FDA = Federal Drug AdministrationFood and Drug AdministrationPart of Department (Ministry) of Health and Human Services Secretary (Minister) part of President’s cabinet (Kathleen Sibelius)Commissioner of Food and Drugs – (Dr Margaret Hamburg) appointed by President, confirmed by Senate, responsible to Secretary – politicals / career CDC, NIH, others also part of DHHS (FDA is the only regulatory body in DHHS)Our secretary & commissioner are not part of our Congress (not a parliamentary system)

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FDA - Components~12,000 employees (~7500 in Washington)Office of the Commissioner (OC)Office of Regulatory Affairs (ORA) (inspectorate/enforcement)Center for Devices and Radiologic Health (CDRH)Center for Veterinary Medicine (CVM)Center for Food Safety and Applied Nutrition (CFSAN)National Center for Toxicologic Research (NCTR)Center for Tobacco ProductsCenter for Biologics Evaluation and Research (CBER)Center for Drug Evaluation and Research (CDER)

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Two medicines laws

U.S. Public Health Service Act (1902)Most biologically derived human medicines

Biosimilars (2010)

Federal Food, Drug, and Cosmetic Act (1938)Most chemically derived human and animal medicines

Generic Drugs (1984)

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NEW MEDICINE DEVELOPMENT

Dis

cove

ry /

Scr

een

ing

SynthesisandPurification

Animal Testing

Pre-clinicalResearch

IND Clinical Studies

Short-term

Long-term

Phase 1

Phase 2

Phase 3

MA

A R

evie

w

Pos

t-au

thor

isat

ion

MA“NDA”

AP

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IND PROCESS(IND = Investigational New Drug)

Submit IND application before 1st clinical study in the US (no matter what “phase” the first study is)

Regulatory vehicle under which all investigational trials are overseen in the USAAll animal data, previous clinical data outside USA (if any), development plan, and first protocol with special emphasis on any safety concerns and manufacturing process for clinical trials suppliesMake case for why it is reasonable to proceed into humans at this point and why the plan for safety monitoring is adequateInclude IRB (ethics committee) oversight information (name)

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IND PROCESSAfter 1st submission – must wait 30 calendar days.

If nothing heard from FDA, may proceed on day 31. Do not need to wait for authorising letter. In fact, there is no “authorising letter”

Subsequent submissions are all “notifications”. Do not need to wait to start trial, simply notify.

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IND PROCESSFDA can place any trial (or part of a trial) on “hold” at any time

“Hold” means trial may not proceed and, if started, no further patients may be enrolled

If application not completeIf FDA does not believe it is reasonably safe to proceedIf FDA does not believe company is properly monitoring for potential safety problemsIf FDA believes trial design puts patients at risk for no scientific purpose (vs not going to answer the question the company wants to have answered)

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WHY DO WE DO THIS?Promote and Protect Public health – clinical trials are how we initially learn about the safety and efficacy of new products

Need independent oversight to help assure that subjects are not put at unreasonable risk and not put into trials from which we cannot reasonably expect to learn something scientifically relevant

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WHY DO COMPANIES ENGAGE WITH US FDA

DURING DEVELOPMENT

Submissions are required

Essentially all engage much more than minimally required

No direct cost for such meetings

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FDA / SPONSORS DURING DRUG DEVELOPMENT

Interact with sponsors to maximise efficiency and scientific robustness of their drug development program

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VERY IMPORTANT:PRE-IND / END OF PHASE 2Reach Understanding of Development Goals and ImplementationTrial designs / Where to do themEvaluability CriteriaDefine a “Win”

Characterise ProductIndications, Dosing Regimen(s)Major Safety ParametersManufacturing Issues

Possible modifications with time

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SPECIAL PROTOCOLSCarcinogenicityStabilityP3 trials that will be primary data for an efficacy claim

Performance goal: 45 daysWritten agreements binding except when science changes

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When can a product be authorised?

When the data show that the demonstrated benefits outweigh the known risks for the intended population when used as directed

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EARLY ACCESS INITIATIVESD

isco

very

/ S

cree

nin

g

SynthesisandPurification

Animal Testing

Pre-clinicalResearch

IND subm

Clinical Studies

Short-term

Long-term

Phase 1

Phase 2

Phase 3

MA

A R

evie

w

Pos

t-au

thor

isat

ion

AP

Subpart E:Submit MA here

Accelerated Approval:

Priority ReviewFast Track-Rolling Review

Treatment IND

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US - EU COMPARISON(Nomenclature)

United StatesPriority Review

Accelerated Approval (Subpart H)

Subpart E

Fast Track

European UnionFast Track

Conditional Approval

Approval under special circumstances

No equivalent

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Thank You / Merci / Dank U

Questions?

Comments?