Bioavailability and Bioequivalence
Bioavailability and bioequivalence assessments of formulations are components of the marketing authorization/approval process for drug products. New Drug Applications (NDAs) of innovator drugs typically include bioavailability and bioequivalence testing, while Abbreviated New Drug Applications (ANDAs) of generic drugs typically include bioequivalence testing. After approval, innovator and generic drugs rely on bioequivalence testing to assure ongoing product quality when manufacturing changes occur. Bioavailability and bioequivalence focus on the release of the drug substance from a drug product and the subsequent absorption into the systemic circulation. Therefore, bioequivalence approaches generally follow approaches for bioavailability. The purpose of establishing bioequivalence is to demonstrate equivalence in biopharmaceutics quality between the proposed and existing drug product (e.g., generic versus brand, post-change versus pre-change product). Therefore, bioequivalence testing typically eliminates the need for preclinical tests and clinical trials. The basic principles and approaches of evaluating bioavailability and bioequivalence are discussed.
KeywordsBioavailability Bioequivalence Pharmacokinetics AUC Cmax Absorption Study design Generics Biowaiver Biopharmaceutics Classification System
- 21CFR314.3. Accessed 28 Aug 2017. https://www.ecfr.gov/cgi-bin/text-idx?SID=d1173eb1e0b5c9151b05905ffe183de3&mc=true&node=se21.5.314_13&rgn=div8.
- 21CFR320.22. Accessed 28 Aug 2017. https://www.ecfr.gov/cgi-bin/text-idx?SID=d1173eb1e0b5c9151b05905ffe183de3&mc=true&node=se21.5.320_122&rgn=div8.
- European Medicines Agency (2010) Guideline on the investigation of bioequivalence. Accessed 28 Aug 2017. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf.Google Scholar
- U.S. Food & Drug Administration (1997) Guidance for industry, dissolution testing of immediate release solid oral dosage forms. Accessed 28 Aug 2017. https://www.fda.gov/downloads/drugs/guidances/ucm070237.pdf.Google Scholar
- U.S. Food & Drug Administration (2001) Guidance for industry, statistical approaches to establishing bioequivalence. Accessed 28 Aug 2017. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070244.pdf.Google Scholar
- U.S. Food & Drug Administration (2011) Guidance on zolpidem. Accessed 28 Aug 2017. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM175029.pdf.Google Scholar
- U.S. Food & Drug Administration (2013) Guidance for industry, bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA. Accessed 28 Aug 2017. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM377465.pdf.Google Scholar
- U.S. Food & Drug Administration (2014) Guidance for industry, bioavailability and bioequivalence studies submitted in NDAs or INDs – general considerations. Accessed 28 Aug 2017. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM389370.pdf.Google Scholar
- U.S. Food & Drug Administration (2015a) Drug development and review definitions. Accessed 28 Aug 2017. https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/ucm176522.htm.Google Scholar
- U.S. Food & Drug Administration (2015b) Guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. Accessed 28 Aug 2017. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf.Google Scholar
- U.S. Food & Drug Administration (2017a) Approved drug products with therapeutic equivalence evaluations. 37th edn. Accessed 28 Aug 2017. https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/UCM071436.pdf.
- U.S. Food & Drug Administration (2017b) What is the approval process for generic drugs? Accessed 28 Aug 2017. https://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingGenericDrugs/ucm506040.htm.Google Scholar
- U.S. Food & Drug Administration (2017c) Generic drugs: questions & answers. Accessed 28 Aug 2017. https://www.fda.gov/drugs/resourcesforyou/consumers/questionsanswers/ucm100100.htm.Google Scholar