WHITE PAPER: Bioassays: Fundamental to an integrated bioequivalence approach


The use of generic medicines can help to alleviate drug shortages, reduce costs, and enhance patient access to treatment. Greater than 80% of drugs prescribed in the USA are currently generic. Therapeutic equivalence (TE) is generally assured by achieving both pharmaceutical equivalence (PE) and bioequivalence (BE) of the generic drug to the reference listed drug (RLD). The traditional paradigm of equivalence works well for systemically absorbed drugs. However, this approach for bioequivalence limits the availability of generic versions of complex drug products (complex generic drug products (CGDPs)), such as ophthalmic, topical, and inhaled drugs. The implementation of BE requirements using clinical studies is prohibitively expensive and the least sensitive method for demonstrating bioequivalence. It is, therefore, crucial to identify and develop alternate [in vitro] methods that can support the development and approval of complex generics. Here we highlight the strengths of a bioequivalence approach, where bioassays are used in conjunction with other methods. These multiple orthogonal and successive end-point measurements provide a totality of evidence that supports regulatory approval, mitigates the risks associated with standalone tests, and improves confidence in bioequivalence.