This chapter provides recommendations for the in vivo and in vitro assessment of drug product performance. The chapter is intended as a guide to scientists and clinicians seeking to evaluate drug product performance by surrogate procedures correlative and/or antecedent to clinical trials in humans. USP–NF provides quality standards for drug substances, excipients, and finished preparations. A USP–NF monograph for an official substance or preparation includes the article's definition; packaging, storage, and other requirements; and a specification. The specification consists of a series of universal tests (description, identification, impurities, and assay) and specific tests, one or more analytical procedures for each test, and acceptance criteria. Quality standards are important attributes that must be built into the drug product. Meeting USP–NF standards is accepted globally as assurance of high quality and is part of the requirements necessary for approval of a bioequivalent (BE), interchangeable multisource drug product. Multisource drug products must meet certain in vivo and/or in vitro performance standards to be considered therapeutically equivalent and interchangeable. Regulatory approval for interchangeable multisource products may differ somewhat in each country (see the forthcoming chapter Essentials for Drug Product Selection 1096 for further discussion). Drug product performance may be defined as the release of the active pharmaceutical ingredient (API) from the drug product dosage form, leading to systemic availability of the API necessary for achieving a desired therapeutic response. This chapter discusses in vivo and in vitro approaches to determining drug product performance. The focus of the chapter is primarily on the performance of solid oral drug products.
The chapter references a Food and Drug Administration (FDA) guidance, Guidance for Industry—Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations (2003) (; search by document title) and a World Health Organization (WHO) document titled Annex 7 Multisource (Generic) Pharmaceutical Products: Guidelines on Registration Requirements to Establish Interchangeability (2006) (; search by document title). FDA guidances are used in the United States; and WHO, FDA, and national/regional guidelines may be used by national/regional drug regulatory authorities. Following approval, control of the quality of a drug product can be achieved in part by the private and/or public specification, which can include a performance test. USP provides the general chapters Disintegration 701, Dissolution 711, Drug Release 724, In Vitro and In Vivo Evaluation of Dosage Forms 1088, and The Dissolution Procedure: Development and Validation 1092, which describe these tests and procedures.
This chapter provides general information about the conduct of bioequivalence (BE) studies as a surrogate measure of in vivo drug product performance and dissolution profile comparisons as a measure of in vitro drug product performance. The chapter also discusses conditions when an in vivo BE requirement may be waived (biowaiver) for certain drug products and shows how the Biopharmaceutics Classification System (BCS) can be used as a predictor of a drug product's performance. An appendix to this chapter defines key scientific terminology and provides a comparison between FDA and WHO in drug product performance assessment.