Colleton, Curtis, Brewster, David, Chester, Anne, Clarke, David, Heining, Peter and Olaharski, Andrew (2016) THE USE OF MINIPIGS FOR PRECLINICAL SAFETY ASSESSMENT BY THE PHARMACEUTICAL INDUSTRY: Results of an IQ DruSafe Minipig Survey. THE USE OF MINIPIGS FOR PRECLINICAL SAFETY ASSESSMENT BY THE PHARMACEUTICAL INDUSTRY: Results of an IQ DruSafe Minipig Survey, 44 (3). pp. 458-466. ISSN 0192-62331533-1601

Abstract

The use of minipigs in preclinical safety testing of pharmaceuticals is considered an alternative to the more traditional dog and non-human primate (NHP) nonrodent species. While the decision to use minipigs may be driven by efforts to reduce or replace the use of dogs and NHPs in biomedical research, substantial evidence exists to suggest that the anatomy, physiology, and biochemistry of minipigs is similar enough to humans to consider them to be valid nonrodent models for pharmaceutical safety testing. Since the utilization of minipigs was last assessed over 5 years ago, the Preclinical Safety Leadership Group (DruSafe) of the International Consortium for Innovation and Quality in Pharmaceutical Development conducted this survey to provide an updated assessment of the utility, perceived value and impediments to the use of minipigs in preclinical safety testing from a representative cross-section of pharmaceutical companies. Of the 32 participating members of DruSafe, 15 responded to the survey representing both large and small companies. Respondents indicated that the minipig has been utilized mostly for short term safety assessment studies with dermal, oral, and parenteral routes of administration. Minipigs are widely accepted as appropriate models for cardiovascular assessments, and have been used to a limited extent for reproductive toxicology testing. Although there were no specific questions regarding the extent to which the minipig has been employed for safety assessment of biologics, the overall responses indicated that pharmaceutical safety testing for large molecules using this species is relatively low. The key reasons cited for this were a lack of background data, lack of reagents or biomarkers to study toxicity and/or pharmacodynamic mechanism of action, concerns regarding immune system characterization and evaluation, and poor suitability for developmental toxicity assessments due to the lack of placental transfer of antibodies.
For GLP studies, most companies utilize Contract Research Organizations (CROs) which offer technical experience, adequate housing, and appropriate historical control databases for definitive safety assessment studies. When minipigs are used for safety assessment the results of definitive studies have been accepted by various worldwide health authorities. Recognizing the limitations of making broad conclusions based on 15 company participants, the conclusions of this survey indicate that while the minipig is an acceptable nonrodent species for the safety testing of pharmaceuticals, their use is largely limited to small molecules, primarily dermal products, and has not substantively increased more broadly since the last industry survey conducted over 5 years ago.

Item Type:	Article
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/27202