February 2, 2004February 2, 2004

Pediatric Drug Development:Pediatric Drug Development: A Decade of Progress: 1994-2004 A Decade of Progress: 1994-2004

Susan K. Cummins, MD, MPHSusan K. Cummins, MD, MPH

Medical Team LeaderMedical Team LeaderDivision of Pediatric Drug DevelopmentDivision of Pediatric Drug Development

Center for Drug Evaluation and ResearchCenter for Drug Evaluation and Research

Today’s TalkToday’s Talk

• Review legal milestones of the last decadeReview legal milestones of the last decade

· 1994 Pediatric Rule1994 Pediatric Rule

· 1997 FDAMA1997 FDAMA

· 2002 BPCA2002 BPCA

· 2003 PREA2003 PREA

• Review Written Request ProcessReview Written Request Process

• Discuss statistics, goals & available resourcesDiscuss statistics, goals & available resources

AcronymsAcronyms

• FDAMAFDAMA – Food & Drug Admin Modernization Act – Food & Drug Admin Modernization Act

• BPCABPCA – Best Pharmaceuticals for Children Act– Best Pharmaceuticals for Children Act

• PREAPREA – Pediatric Research Equity Act– Pediatric Research Equity Act

• WR WR – Written Request– Written Request

• PPSR PPSR – Proposed Pediatric Study Request– Proposed Pediatric Study Request

1994 Pediatric Regulations 1994 Pediatric Regulations

• Required sponsor review of available pediatric Required sponsor review of available pediatric data to determine whether existing data was data to determine whether existing data was adequate to support pediatric labelingadequate to support pediatric labeling

• No clinical studies requiredNo clinical studies required

• Introduced concept of extrapolation of efficacy Introduced concept of extrapolation of efficacy data from adults to childrendata from adults to children

1997 FDAMA Pediatric 1997 FDAMA Pediatric ProvisionsProvisions

• Created pediatric exclusivity incentives based Created pediatric exclusivity incentives based on Written Request from FDAon Written Request from FDA

• Sunset on January 1, 2002Sunset on January 1, 2002

What is “Pediatric Exclusivity”?What is “Pediatric Exclusivity”?• An additional 6-month period during which a sponsor An additional 6-month period during which a sponsor

retains exclusive marketing control of all forms of a retains exclusive marketing control of all forms of a drug product linedrug product line

• Requires either an existing patent or existing Requires either an existing patent or existing exclusivityexclusivity

• Confers to the entire moietyConfers to the entire moiety

• Substantial financial incentive Substantial financial incentive

• Delays introduction of generic productsDelays introduction of generic products

FDAMA “Priority List”FDAMA “Priority List”

• Issued by FDAIssued by FDA

• Being on the priority list did not require a WR Being on the priority list did not require a WR to be issuedto be issued

• Sunset on January 1, 2002Sunset on January 1, 2002

2002 Best Pharmaceuticals for 2002 Best Pharmaceuticals for Children ActChildren Act

• Became law January 4, 2002Became law January 4, 2002

• Re-authorizes exclusivity incentive program Re-authorizes exclusivity incentive program under FDAMA under FDAMA

• Includes an additional mechanism for Includes an additional mechanism for obtaining information on safe and efficacious obtaining information on safe and efficacious use of drugs in pediatric populations for use of drugs in pediatric populations for off-patent drugsoff-patent drugs

Two Paths to a Written RequestTwo Paths to a Written Request

• FDA generates and issues a WRFDA generates and issues a WR

• PPSR sent to FDA by industryPPSR sent to FDA by industry

· FDA FDA acceptsaccepts proposal and issues WR proposal and issues WR

· FDA FDA modifiesmodifies proposal and issues WR proposal and issues WR

· FDA FDA does not acceptdoes not accept proposal and issues proposal and issues inadequate letterinadequate letter

Written RequestWritten Request• A (legal) document sent by the FDA to sponsors A (legal) document sent by the FDA to sponsors requesting studies in the pediatric populationrequesting studies in the pediatric population

• Specifies: Specifies:

· indicationindication

·populationpopulation

· type of studiestype of studies

· safety parameterssafety parameters

· longer term follow-uplonger term follow-up

· timeframe for responsetimeframe for response

Process for the Study ofProcess for the Study ofOn-Patent Drugs under BPCAOn-Patent Drugs under BPCA

FDA issues Written Request

Industry submits Proposed Pediatric Study Request

FDA determines if there is a public health benefit

yes

no

FDA issues Inadequate Letter

Process for the Study of On-Patent Process for the Study of On-Patent Drugs under BPCA Drugs under BPCA (cont.)(cont.)

FDA issues Written Request

Industry agrees to conduct studies

Industry declinesto conduct studies

Possible Referral to Foundation for NIH

Industry has 180 days to respond

yes

no

Process for the Study of On-Patent Process for the Study of On-Patent Drugs under BPCA Drugs under BPCA (cont.)(cont.)

Referral to Foundation for NIH

Foundation conducts studies

Foundation lacks funds to conduct

studies

WR referred to NIH for inclusion on List

FDA On-Patent Drug Exclusivity ProcessFDA On-Patent Drug Exclusivity ProcessBackground Research/Extensive Literature ReviewBackground Research/Extensive Literature Review

SponsorSponsor Proposed PediatricProposed Pediatric Development of Written Development of Written

Request Study Request (PPSR)Request Study Request (PPSR) by Reviewing Divisionby Reviewing Division

Reviewed by PdIT Reviewed by PdIT

FDAFDA WR Issued WR Issued

Sponsor Completes StudiesSponsor Completes Studies

or FDAor FDA Exclusivity Determined byExclusivity Determined byExclusivity Board (60-90 days)Exclusivity Board (60-90 days)

Action on Application (6-10 Action on Application (6-10 months) – includes label months) – includes label negotiations with sponsornegotiations with sponsor

Progress: Industry Response as of Progress: Industry Response as of January 2004January 2004

• Proposals from IndustryProposals from Industry 336336

• FDA-issued Written RequestsFDA-issued Written Requests 283 283

• Exclusivity DeterminationsExclusivity Determinations 101101

• Exclusivity GrantedExclusivity Granted 9191

• New LabelsNew Labels 6363

2003 Pediatric Research Equity Act2003 Pediatric Research Equity Act

• Became law December 3, 2003Became law December 3, 2003

• Legislation mimics Pediatric RuleLegislation mimics Pediatric Rule

• Retroactive for all applications back to Retroactive for all applications back to April 1, 1999April 1, 1999

Pediatric Research Equity Act Pediatric Research Equity Act

• Requires pediatric studies of certain drugs & Requires pediatric studies of certain drugs & biological productsbiological products

·New indicationNew indication

·New dosage form New dosage form

·New routeNew route

·New dosing regimenNew dosing regimen

·New active ingredientNew active ingredient

• FDA Guidance under developmentFDA Guidance under development

• Establishes Pediatric Advisory CommitteeEstablishes Pediatric Advisory Committee

GoalGoal

On-Patent Exclusivity ProcessOn-Patent Exclusivity Process

andand

Off-Patent BPCA ProcessOff-Patent BPCA Process

New Pediatric Information in LabelNew Pediatric Information in Label

FDA Web PageFDA Web Page

Link to Peds page

www.fda.gov

Pediatric Web PagePediatric Web Page