Challenges associated with the evaluation of veterinary product bioequivalence: an AAVPT perspective

Abstract

The Generic Animal Drug Patent Term Restoration Act (GADPTRA) enacted in 1988 provided the same benefits to animal drug products that were granted to human generic products. It has been over 13 years since the GADPTRA was enacted, and veterinary drug sponsors and regulators have gained enormous insight and experience into some of the unique challenges associated with the determination of product bioequivalence for veterinary dosage forms. Moreover, advances in information and technology have opened both new issues that must be addressed and new mechanisms for demonstrating product bioequivalence. While many aspects of the existing Center for Veterinary Medicine Bioequivalence Guidance continue to provide invaluable guidance to the animal drug industry, there are also aspects of this guidance that are being called into question. Therefore, during the 2001 annual meeting of the American Academy of Veterinary Pharmacology and Therapeutics, participants were asked to address issues and concerns associated with the evaluation of veterinary product bioequivalence. This manuscript provides a summary of the concerns and discussions that transpired.

Pharmacokinetics and Bioequivalence of Florfenicol Oral Solution Formulations (Flonicol® and Veterin®10%) in Broiler Chickens

“…In this respect, generic pharmaceutical preparations of florfenicol seeking approval to enter the market should demonstrate their ability to achieve C max and AUC values that are equivalent to that of the original preparation. Inability to maintain high enough concentrations for sufficient periods of time may lead to therapeutic failure and may encourage the proliferation of resistant micro-organisms [19,23]. In this study, the pharmacokinetics and bioequivalence of two oral florfenicol solutions (Flonicol ® and Veterin ® 10%) were investigated in healthy broiler chickens at a dose rate of 20mg/kg bw according to the manufacture's recommendations.…”

“…In order to optimize the clinical outcome and to minimize the development of bacterial resistance, the copied pharmaceutical preparations must be bioequivalent to the innovator product [19,20]. These issues have become an on-going subject of concern within the European Community and the United States of America for registering new and generic drug products [19,[21][22][23].…”

Establishing bioequivalence of veterinary premixes (Type A medicated articles)

“…These factors were considered at the 2001 meeting of the American Academy of Veterinary Pharmacology and Therapeutics and reported by Martinez et al. (2002a).…”

“…the Chemistry Manufacturing and Controls), this is not the case in many other regions of the world, as segregation, homogeneity and other feed mixing requirements are neither evaluated nor required for a generic premix. Moreover, this group pointed out that in vitro dissolution testing would be difficult, though not impossible, to conduct because of the clumping behaviour of food substances (Martinez et al. , 2002a).…”

“…These factors were considered at the 2001 meeting of the American Academy of Veterinary Pharmacology and Therapeutics and reported by Martinez et al (2002a). It was agreed that drug administered in feed presented a unique challenge in the assessment of bioequivalence.…”