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
495138
DRUG MARKETING/FDA APPROVAL PROCESS1906 1938 1962 1972 1984 20??
DRUG (MARKET)
DRUG (MARKET) [ DESI II List ]SAFE / GRAS
SAFETY NOT ESTABLISHED (NDA)NAS/NRC
PANELREVIEW
(DESI) ANDAW/O BIOSTUDY
SAFE & EFFECTIVEGRAS & E (MARKET)
SAFETY AND/OREFFECTIVENESS
NOTESTABLISHED
(NDA)ANDA IF
EQUIVALENTBIOSTUDY
DRUG
OTC REVIEWESTABLISHES
GRAS & E(MARKET)
SAFETY AND/OREFFECTIVENESS
NOTESTABLISHED
ANDA IFEQUIVALENT
BIOSTUDY
(NDA)
DRUG(OTC)
DRUG-NDA
[ DESI II List ]
[ DESI II List ]
ANDA IF BIOEQUIV AND PATENT OR EXCLUSIVITY RIGHT EXPIRED
Courtesy of K&L Gates
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