title: Biopharmaceutics classification system-based biowaivers for generic oncology drug products: case studies.
abstract: Establishing bioequivalence (BE) of drugs indicated to treat cancer poses special challenges. For ethical reasons, often, the studies need to be conducted in cancer patients rather than in healthy volunteers, especially when the drug is cytotoxic. The Biopharmaceutics Classification System (BCS) introduced by Amidon (1) and adopted by the FDA, presents opportunities to avoid conducting the bioequivalence studies in humans. This paper analyzes the application of the BCS approach by the generic pharmaceutical industry and the FDA to oncology drug products. To date, the FDA has granted BCS-based biowaivers for several drug products involving at least four different drug substances, used to treat cancer. Compared to in vivo BE studies, development of data to justify BCS waivers is considered somewhat easier, faster, and more cost effective. However, the FDA experience shows that the approval times for applications containing in vitro studies to support the BCS-based biowaivers are often as long as the applications containing in vivo BE studies, primarily because of inadequate information in the submissions. This paper deliberates some common causes for the delays in the approval of applications requesting BCS-based biowaivers for oncology drug products. Scientific considerations of conducting a non-BCS-based in vivo BE study for generic oncology drug products are also discussed. It is hoped that the information provided in our study would help the applicants to improve the quality of ANDA submissions in the future.
authors.affiliation: Division of Bioequivalence, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA, Nilufer.Tampal@fda.hhs.gov.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Tampal
authors.forename: Haritha
authors.initials: H
authors.lastname: Mandula
authors.forename: Hongling
authors.initials: H
authors.lastname: Zhang
authors.forename: Bing V
authors.initials: BV
authors.lastname: Li
authors.forename: Hoainhon
authors.initials: H
authors.lastname: Nguyen
authors.forename: Dale P
authors.initials: DP
authors.lastname: Conner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000145:classification* / Q000493:pharmacokinetics* / Q000592:standards; D001702:Biopharmaceutics / Q000331:legislation & jurisprudence* / Q000592:standards; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D016568:Drugs, Generic / Q000145:classification* / Q000493:pharmacokinetics / Q000592:standards; D006801:Humans; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence*
chemical_list: D000970:Antineoplastic Agents; D016568:Drugs, Generic