The occurrence of drugs and drug formulations associated with large intrasubject pharmacokinetic (PK) variability has been well described in humans and is likewise encountered in veterinary medicine. The scaled average bioequivalence (SABE) approach adopted by CDER of the FDA for the determination of bioequivalence (BE) of highly variable drugs (HVD) needs to be considered when applied to veterinary dosage forms. However, because of some of the unique challenges that are encountered within the framework of veterinary medicine, variations of CDER's approach are presented. The present manuscript discusses HVD and highly variable veterinary drugs (HVVD) from the perspective of possible alternative approaches to support the assessment of product BE in veterinary medicine. Limitations in the use of 3- and 4-way crossover study designs are enumerated. In addition to a need for a statistical analysis of HVVD when using a parallel study design, the use of the secondary criteria (test-to-reference ratio), definition of σ(0) , and average BE with expanding limits are raised. A number of the details need to be finalized, from the selection of a regulatory constant to the determination of 'highly variable' in a veterinary drug product. Academicians, industrial scientists, and regulators should continue this discussion and resolve these details.

Journal of Veterinary Pharmacology and TherapeuticsVolume 34, Issue 2 p. 105-107 MEETING REPORT The 2010 AAVPT/EAVPT/ECVPT bioequivalence workshop M. MARTINEZ, M. MARTINEZ FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorR. P. HUNTER, R. P. HUNTER FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorR. BAYNES, R. BAYNES FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorE. BERMINGHAM, E. BERMINGHAM FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorR. CLAXTON, R. CLAXTON FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorC. COLE, C. COLE FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorJ. Del CASTILLO, J. Del CASTILLO FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorR. GEHRING, R. GEHRING FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorK. HARSHMAN, K. HARSHMAN FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorC. LAINESSE, C. LAINESSE FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorA. LUCAS, A. LUCAS FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorS. MODRIC, S. MODRIC FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorJ. ROBINSON, J. ROBINSON FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this author M. MARTINEZ, M. MARTINEZ FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorR. P. HUNTER, R. P. HUNTER FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorR. BAYNES, R. BAYNES FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorE. BERMINGHAM, E. BERMINGHAM FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorR. CLAXTON, R. CLAXTON FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorC. COLE, C. COLE FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorJ. Del CASTILLO, J. Del CASTILLO FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorR. GEHRING, R. GEHRING FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorK. HARSHMAN, K. HARSHMAN FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorC. LAINESSE, C. LAINESSE FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorA. LUCAS, A. LUCAS FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorS. MODRIC, S. MODRIC FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this authorJ. ROBINSON, J. ROBINSON FDA/CVM, HFV-130, Standish Place, Rockville, MD, USASearch for more papers by this author First published: 17 February 2011 https://doi.org/10.1111/j.1365-2885.2011.01281.xCitations: 3 Dr Marilyn Martinez, FDA/CVM, HFV-130, 7500 Standish Place, Rockville, MD 20855, USA. E-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume34, Issue2April 2011Pages 105-107 RelatedInformation

The American Academy of Veterinary Pharmacology and Therapeutics (AAVPT) and the United States Pharmacopeia (USP) co-sponsored a workshop to explore approaches for developing companion animal antimicrobials. This workshop was developed in response to the shortage of antimicrobials labeled for dogs and cats, as there is a shortage of approved antimicrobials for the range of infectious diseases commonly treated in small animal practice. The objective of the workshop was to identify alternative approaches to data development to support new indications consistent with the unmet therapeutic needs of dogs and cats. The indications for currently approved antimicrobials do not reflect the broader range of infectious diseases that are commonly diagnosed and treated by the veterinarian. Therefore, the labels for these approved antimicrobials provide limited information to the veterinarian for appropriate therapeutic decision-making beyond the few indications listed. Industry, veterinary practice, and regulatory challenges to the development of new antimicrobial indications were discussed. The workshop resulted in short- and long-term recommendations. Short-term recommendations focus on the use of additional data considerations for product labeling. Long-term recommendations center on legislative or regulatory legal initiatives. The workshop recommendations will need collaboration from industry, academia, and regulatory authorities and a legal shift in the drug approval and availability processes.