Service Description

WuXi AppTec was contracted to perform GLP-compliant IND-enabling safety pharmacology and toxicology studies to support first in human dosing of a small molecule. This included method validation for analysis of dose formulations and bioanalytical method validation in rodent and large animal plasma.

What Went Well

Wuxi AppTec did a good job with the method validation (dose formulation, bionanalytical method validation in rodent and large animal plasma). In addition, due to concerns regarding diet sourced from China, Wuxi AppTec allowed certified diet from a US vendor to be used on study. Also, the histopathologic examination was provided by a board certified anatomic pathologist in the US. For work sourced at Suzhou, the study directors provided timely updates to the Sponsor, at the Sponsor's request.

What Could Be Improved

The Shanghai site stored the test article incorrectly (misunderstood what "ambient storage" meant on the label). This required retest of the remaining test article and this incorrect storage was not discovered/communicated to the Sponsor until after the dosing was completed. The Suzhou site used syringes in sampling dose formulations dissolved in dimethlysulfoxide, a strong solvent, which resulted in contamination, invalidation of two in vitro studies, and repeat of both studies using polypropylene pipet tips for sampling of dose formulations. Protocols were not always drafted as soon as the Sponsor preferred, such that there was not sufficient time for the Sponsor to provide a thorough review. Overall, the experience of this CRO is less than that of other major CROs in North America and Europe, and in particular, cardiovascular safety pharmacology conduct and evaluation were suboptimal.

Lessons Learned from the Experience

The Sponsor learned that due to the overall lower experience of this CRO, much does need to be explained up front and in a protocol, in an effort to avoid potential pitfalls during the conduct of the study. There is much turnover at the facility, including that of senior management, and as with any other CRO, reassessment of current capability is important before placement of future studies.