title: Review of Transporter-Related Postmarketing Requirement or Postmarketing Commitment Studies.
abstract: The objectives of this report are to summarize the content and status of transporter-related postmarketing requirement (PMR)/postmarketing commitment (PMC) studies in new drug applications (NDAs) approved by the U.S. Food and Drug Administration (FDA) and to discuss the reasons for requesting such studies and the impact of PMR/PMC study results on labeling to guide the optimal use of the drugs. Multiple data sources were searched to collect information on transporter-related PMR/PMC studies between January 1999 and May 2015. A total of 40 transporter-related PMR/PMC study requests were issued for 35 NDAs. Among these PMR/PMC studies, 27 requested studies related to P-glycoprotein. As of May 31, 2015, 34 transporter-related PMR/PMC studies (85%) are considered "fulfilled" (per the FDA's PMR/PMC website), and 22 (65%) resulted in labeling updates. The majority of the PMR/PMC studies are for drugs in the therapeutic areas of anti-infectives, oncology, and neurology. The results from PMR/PMC studies are important for dosing optimization and are often included in the updated labeling. Because a significant lag time is anticipated between drug approval and PMR/PMC fulfillment, NDA applicants are encouraged to include transporter-related assessments in clinical drug development programs for drug products.
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.|Current Affiliation: Office of Bioequivalence, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.|Oak Ridge Institution for Science and Education (ORISE) Fellow, Oak Ridge, TN, USA.|Current Affiliation: Department of Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017277:Drug Approval / Q000331:legislation & jurisprudence* / Q000379:methods*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011358:Product Surveillance, Postmarketing / Q000379:methods* / Q000639:trends; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence* / Q000639:trends
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations
keywords: drug-drug interaction (DDI); labeling; new molecular entity (NME); postmarketing commitment (PMC); postmarketing requirement (PMR); regulatory; transporters