1. Overview of FDA's Regulatory Compliance Agenda Daniel Meron, Esq. General Counsel Department of Health and Human Services August 22, 2007

2. Topics Regulation of Drug Compounding Regulation of Drug Compounding Enforcement Regarding Unapproved Drugs Enforcement Regarding Unapproved Drugs Off-Label Promotion Investigations and Enforcement Off-Label Promotion Investigations and Enforcement Preemption Preemption

3. Drug Compounding Traditional drug compounding Traditional drug compounding FDCA definition of “new drug”: FDCA definition of “new drug”: Any drug the composition of which is not generally recognized as safe and effectiveAny drug the composition of which is not generally recognized as safe and effective FDA’s enforcement discretion policy FDA’s enforcement discretion policy Traditionally defer to state regulation regarding compounded drugsTraditionally defer to state regulation regarding compounded drugs 1992 Compliance Policy Guide (CPG)1992 Compliance Policy Guide (CPG)

4. Drug Compounding FDCA Section 503A: exempted compounded drugs from certain requirements of the FDCA, including new drug approval, if: FDCA Section 503A: exempted compounded drugs from certain requirements of the FDCA, including new drug approval, if: Drugs compounded in response to a valid prescription for an identified patientDrugs compounded in response to a valid prescription for an identified patient Prepared in “limited quantities” in advance of prescriptions based on a history of receiving prescriptions for that productPrepared in “limited quantities” in advance of prescriptions based on a history of receiving prescriptions for that product Prohibited advertising the availability of specific compounded drugs or soliciting prescriptions Prohibited advertising the availability of specific compounded drugs or soliciting prescriptions

5. Drug Compounding Thompson v. Western States Med. Center Thompson v. Western States Med. Center Speech provisions of 503A are unconstitutionalSpeech provisions of 503A are unconstitutional Ninth Circuit: Speech provisions cannot be severedNinth Circuit: Speech provisions cannot be severed 2002 Compliance Policy Guide 2002 Compliance Policy Guide Medical Center Pharmacy v. Gonzales Medical Center Pharmacy v. Gonzales District Court holding:District Court holding: Section 503A is valid Section 503A is valid FDCA implicitly exempts compounded drugs from the definition of “new drugs” FDCA implicitly exempts compounded drugs from the definition of “new drugs” On appeal to the Fifth CircuitOn appeal to the Fifth Circuit

6. Unapproved Drugs Prevalence of unapproved drugs Prevalence of unapproved drugs 2006 CPG on unapproved drugs 2006 CPG on unapproved drugs Risk-based enforcement strategyRisk-based enforcement strategy Factors that FDA will consider:Factors that FDA will consider: Drugs with potential safety risks Drugs with potential safety risks Drugs that lack evidence of effectiveness Drugs that lack evidence of effectiveness Drugs that are fraudulently promoted Drugs that are fraudulently promoted Drugs that challenge new drug approval process Drugs that challenge new drug approval process Recent enforcement examples Recent enforcement examples

7. Off-Label Promotion Legal background: Legal background: Drugs must be approved for each intended useDrugs must be approved for each intended use Promotion of a drug for an unapproved use can cause it to be misbranded, unapprovedPromotion of a drug for an unapproved use can cause it to be misbranded, unapproved Example: Investigation into off-label promotion for Evista Example: Investigation into off-label promotion for Evista Improper use of reprints to promote off-labelImproper use of reprints to promote off-label Improper use of consultant meetingsImproper use of consultant meetings

8. Preemption FDA approves labeling for a drug, including the precise wording of warnings FDA approves labeling for a drug, including the precise wording of warnings Manufacturer must use FDA-approved labelingManufacturer must use FDA-approved labeling Use of non-FDA-approved labeling could misbrand productUse of non-FDA-approved labeling could misbrand product CBE supplement provision is a limited exception to general rule of advance FDA-approval CBE supplement provision is a limited exception to general rule of advance FDA-approval

9. Colacicco v. Apotex Plaintiff alleged that manufacturer should have provided different warnings regarding suicide risks for paroxetine hydrochloride Plaintiff alleged that manufacturer should have provided different warnings regarding suicide risks for paroxetine hydrochloride FDA had previously considered and rejected stronger warnings FDA had previously considered and rejected stronger warnings FDA’s amicus brief: FDA’s amicus brief: Use of different warnings would have violated federal lawUse of different warnings would have violated federal law CBE supplement would not have been appropriateCBE supplement would not have been appropriate

10. Potential Preemption Cases Before the Supreme Court Riegel v. Medtronic Riegel v. Medtronic Device preemptionDevice preemption Certiorari grantedCertiorari granted Levine v. Wyeth Levine v. Wyeth Drug preemptionDrug preemption Court considering whether to grant certiorariCourt considering whether to grant certiorari