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Center for Professional Advancement
Generic Drug Approvals Course
Introduction to the Legal Basis for
Generic Drug Approvals
Michael A. Swit, Esq.
Vice President
FDA’s Legal Authority
 Statute
 Via US Congress, signed by President
 21 US Code sections 301-399
 Regulations
 Via public notice in Federal Register
 21 Code of Federal Regulations Parts 1-1299
 Guidance Documents
 Via FDA alone
 Good to follow, but not binding on industry
 On FDA’s website, www.fda.gov
Early Statutory Provisions
 The Pure Food and Drugs Act of 1906
 Drug provisions (patented medicines): no misbranding or
adulteration
 The Federal Food, Drug, and Cosmetic Act of 1938
 Defined “drug” and “new drug”
 Created “New Drug Application”
 Required proof of safety and mfg. process info.
 No affirmative FDA approval
 “Me-Too”/Generic drugs had no FDA oversight
Regulations of Drugs, 1962-1984
 The Drug Amendments of 1962 (Kefauver-Harris Drug
Amendments)
 Review NDA requirements
 To add proof of effectiveness (efficacy)
 To add affirmative FDA approval
 Created Drug Efficacy Study Implementation (“DESI”)
Review
 To review safety-only NDAs for efficacy
 Applied to NDA and Me-Too drugs
 Drugs not reviewed yet are known as “DESI II”
Regulations of Drugs, 1962-1984
 Created Abbreviated New Drug Application (“ANDA”)
 Safety and efficacy was assumed
 Required submission of mfg. process info. & labeling
 Outgrowth of DESI process – thus limited in scope
 OTC Drug Review
 Safety and efficacy determined by FDA on a therapeutic class basis
 Marketing permitted if compliance with OTC monograph (active
ingredients, indications, directions, warnings)
 The Paper NDA Policy
 Me-Too drugs established safety and efficacy via published literature,
public data
DRUG MARKETING/FDA APPROVAL PROCESS
1906
DRUG
DRUG
1938
1962
1972
1984
20??
[ DESI II List ]
(MARKET)
SAFE / GRAS
[ DESI II List ]
(MARKET)
SAFETY NOT ESTABLISHED
(NDA)
SAFE & EFFECTIVE
GRAS & E
NAS/NRC
PANEL
REVIEW
ANDA
W/O BIOSTUDY
(DESI)
(MARKET)
[ DESI II List ]
DRUG
SAFETY AND/OR
EFFECTIVENESS
NOT
ESTABLISHED
ANDA IF
EQUIVALENT
BIOSTUDY
(NDA)
OTC REVIEW
ESTABLISHES
GRAS & E
(MARKET)
DRUG
(OTC)
SAFETY AND/OR
EFFECTIVENESS
NOT
ESTABLISHED
DRUG-NDA
Courtesy of K&L Gates
495138
(NDA)
ANDA IF
EQUIVALENT
BIOSTUDY
ANDA IF
BIOEQUIV AND
PATENT OR
EXCLUSIVITY
RIGHT EXPIRED
Statutory Provisions (cont’d)
 The Orphan Drug Act of 1983
 Drugs for rare diseases and disorders in US
 Tax incentives and federal grants
 Awards market monopoly for 7 years
 The Drug Price Competition and Patent Term
Restoration Act of 1984 (Waxman-Hatch Act)
 Revised ANDA to modern day requirements, adds
bioequivalence studies
 Patent extensions and market exclusivity for NDA drugs
505(b)(1) New Drug Application (NDA)
 FDA must pre-approve
 New ingredient (chemical)
 New labeling indication
 New formulation (i.e., transdermal patch)
 Animal and clinical data
 Market protection: patent extension and exclusivity by orphan
drug, new chemical entity, clinical or pediatric studies
505(b)(2) New Drug Application (NDA)
 FDA must pre-approve
 Reference the literature or marketed drug (NDA)
 Data required will be based on unanswered questions (animal
tox – clinical)
 Must file patent certification
 Market protection: patent extension and exclusivity by clinical
or pediatric studies
Abbreviated New Drug Application
(ANDA)
 FDA must preapprove
 Must be based on Reference Listed Drug (NDA)
 Can change strength/dosage/formulation by
petition request
 Bioequivalence data
 Labeling must be identical
 Must file patent certification
OTC Monograph Drug
 No FDA preapproval
 Active ingredients
 Labeling claims
 Dosage limitations
 No market protection
 Must submit labeling to drug listing
DESI II Drugs
 No FDA preapproval
 Must be identical to pre-1984 marketed drug in:
 Ingredient
 Labeling indications
 Formulation
 Dosage form
 No market protection
 Must submit labeling to drug listing
 Regulatory risk
Statutory Provisions (cont’d)
 Generic Drug Enforcement Act of 1992
 Mandatory or permissive debarment for bribery, fraud, conspiracy,
unlawful act
 Temporary denial of ANDA
 Withdrawal of approval of ANDA
 Civil money penalties
 Prescription Drug User Fee Act of 1992
 Applies to NDAs only
 FDA Export Reform and Enhancement Act, 1996
 Import for export without substantial FDA involvement
 APIs, components, unapproved drugs
Statutory Provisions (cont’d)
 FDA Modernization Act of 1997
 Permits “Rx Only” and “FDA Approved” labeling
 Sets up qualifications for FDA application reviewers
 Created pediatric market exclusivity for NDAs with pediatric studies
 Codified permissible post-approval manufacturing changes
 Best Pharmaceuticals for Children Act, 2002
 Reauthorized pediatric exclusivity
 National Preparedness for Bioterrorism, 2002
 Reauthorized user fees
 Pediatric Research Equity Act of 2003
 Gave FDA authority to require pediatric studies
Medicare Prescription Drug Improvement and
Modernization Act of 2003
 Title XI – access to affordable pharmaceuticals
 Implemented changes to sections 505(j) and
505(b)(2) of FDC Act, and Title 35 of Patent Law
 Changed rules for ANDAs containing Paragraph
IV certifications to a patented drug
 Codified bioequivalence definitions from FDA
regulations
 Codified FDA rule permitting bundling of several
strengths under one ANDA