ABSTRACT

Introduction ............................................................................................................ 140 Why Stability for Generic Drugs? ..................................................................... 140 Terminology ...................................................................................................... 141

API Stability........................................................................................................... 141 Pharmacopeial and Nonpharmacopeial APIs .................................................... 141 Specifications and Test Methods ....................................................................... 142 FDA and ICH Guidelines .................................................................................. 143 Issues for Multisource APIs .............................................................................. 143 Method Validation ............................................................................................. 144 Shelf-Life Development and Assignment ......................................................... 144 Packaging .......................................................................................................... 145 Shipment ........................................................................................................... 145

Intermediates for Drug Products ............................................................................ 145 Specifications .................................................................................................... 146 Holding Time .................................................................................................... 146

Drug Product Stability ........................................................................................... 146 Pharmacopeial and Nonpharmacopeial Products .............................................. 147 Specifications and Test Methods ....................................................................... 147 Method Validation ............................................................................................. 148 FDA and ICH Guidelines .................................................................................. 148 Stability Protocol ............................................................................................... 149 Shelf-Life Development .................................................................................... 150 Action Limits .................................................................................................... 150 Expiration Date Assignment ............................................................................. 151 Annual Stability ................................................................................................ 152 Extension of Expiration Dating Period ............................................................. 152 Bulk Holding ..................................................................................................... 152 Bracketing ......................................................................................................... 153 Matrixing ........................................................................................................... 154 Controlled Room Temperature .......................................................................... 156 Stability of Products Containing Iron ............................................................... 156 Reprocessing and Reworking ............................................................................ 157 Packaging .......................................................................................................... 157 Shipment ........................................................................................................... 158

Controlled Drugs .................................................................................................... 158 Storage Requirements for CI to CV Drugs ....................................................... 158

In 1984, the Hatch-Waxman Amendment of the Federal Food, Drug, and Cosmetic Act (the Act) was enacted. This amendment, which is also known as the Drug Price Competition and Patent Term Restoration Act of 1984 (Public Law 98-417), allowed lower priced generic drug equivalents of the off-patent branded drugs in the US marketplace. In this chapter, the US Food and Drug Administration (FDA) requirements governing the stability of generic drugs will be discussed. Stimulated by the growth of the generic industry, a comprehensive journal publication [1] devoted exclusively to the development, manufacturing, quality control, and quality assurance of generic drugs is available in print and on the website.