Keywords: bioequivalence, veterinary, biowaivers, type a medicated articles, premixes
Premixes (Type A medicated articles) are veterinary dosage forms, just as are solutions, suspensions, tablets, capsules, pastes, pour-ons, etc. Premixes are not aqueous solutions and they are not formulated for intravenous administration, so that exclusions from in vivo testing of a generic premix formulation may not apply in all cases. The current criteria for classifying drug solubility are based on human gastrointestinal (GI) physiology. These criteria may not be appropriate to the unique conditions encountered within the GI tract of veterinary species. For generic premix formulations, it is essential that bioequivalence to a pioneer product (with established efficacy, target animal safety and human food safety based on detailed pre-clinical and clinical assessments) is established as for other veterinary medicinal product formulations. There is, however, the possibility of granting waivers from in vivo studies for premix formulations; this is a subject on which there is no general agreement nor internationally harmonized set of guidelines. The CVM/FDA have issued GFI #171, which is currently listed as being under revision. The VICH has issued GL52 for blood level BE only. The key considerations therefore are: (i) should premixes be eligible for consideration of a biowaiver; (ii) if biowaivers can be granted, what are the criteria; (iii) how do dissolution and/or solubility testing methods fit within the criteria; (iv) what is the role of API solubility in the evaluation of premix biowaivers.