title: Product-Specific Regulatory Pathways to Approve Generic Drugs: The Need for Follow-up Studies to Ensure Safety and Effectiveness.
abstract: Generic drugs possessing the same active ingredients, dosage form, strength, route of administration, and labeling can be approved by the US Food and Drug Administration (FDA) as interchangeable with a brand-name drug without needing to repeat the formal Phase I, II, and III clinical trials conducted by the original manufacturers. In recent years, the FDA has approved several generic drugs using product-specific testing to determine therapeutic equivalence in accordance with the unique features of the particular drug. These have been used in two primary situations: (1) cases for which certain bioequivalence studies were not relevant; and (2) cases of complex molecules that may require specially tailored pharmaceutical equivalence studies. Examples include venlafaxine extended release, acarbose, vancomycin capsules, sodium ferric gluconate, salmon calcitonin nasal spray, and enoxaparin. Product-specific approaches to demonstrating therapeutic equivalence are essential to avoid delays in low-cost generic drug availability but can have important clinical implications; yet, currently, there is no formal process in place to monitor the safety and effectiveness of generic drugs approved using modified regulatory pathways. Several strategies can be used to monitor the safety and effectiveness of generic drugs approved via product-specific determinations of therapeutic equivalence.
authors.affiliation: Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Kesselheim
authors.affiliation: Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA. jgagne1@partners.org.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Gagne
mesh_terms: D002986:Clinical Trials as Topic; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D016527:Drug Costs; D016568:Drugs, Generic / Q000627:therapeutic use*; D017984:Enoxaparin / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D012449:Safety / Q000331:legislation & jurisprudence*; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence
chemical_list: D016568:Drugs, Generic; D017984:Enoxaparin