title: Demonstrating comparative in vitro bioequivalence for animal drug products through chemistry and manufacturing controls and physicochemical characterization: a proposal.
abstract: The assessment of in vivo bioequivalence (BE) of nonsystemically absorbed drug products has been a longstanding challenge facing drug manufacturers and regulators of human or animal health products. Typically, in situations where blood level BE studies are not feasible, clinical endpoint BE trials have provided the only option for generating interproduct comparisons. Given the imprecision and logistic challenges associated with these studies, there has been an effort to identify alternative pathways that can reliably ensure the equivalence of product performance and quality. This commentary provides a proposal for an in vitro approach for evaluating the in vivo BE of veterinary drug products that are either nonsystemically absorbed or that act both locally and systemically but where the local site of action is proximal to the absorption window. The assumption underlying this approach is that equivalence in product physicochemical attributes and in vitro product performance translates to equivalence in product in vivo behavior. For sponsors with a right of reference to underlying safety and effectiveness data, this approach could be used to support pre and post-approval changes. When comparing a generic test product to the pioneer (reference listed new animal drug, RLNAD) product, a demonstration of sameness across a battery of in vitro test procedures could be used to confirm that the test and RLNAD products are bioequivalent.
authors.affiliation: USFDA Center for Veterinary Medicine, Office of New Animal Drug Evaluation, 7500 Standish Place, HFV-100, Rockville, Maryland, 20855, USA, marilyn.martinez@fda.hhs.gov.
authors.forename: Marilyn N
authors.initials: MN
authors.lastname: Martinez
authors.forename: Raafat
authors.initials: R
authors.lastname: Fahmy
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D017277:Drug Approval; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D013810:Therapeutic Equivalency; D019155:Veterinary Drugs / Q000493:pharmacokinetics*
chemical_list: D016568:Drugs, Generic; D019155:Veterinary Drugs