In June 2016, the FDA published their Guidance on ISO 10993. The agency is in full enforcement of the guidance and the risk-based approach to preclinical device safety testing. At WuXi AppTec, we have continued to monitor the regulatory trends to understand the approach and enforcement of the guidance by the agency.
One trend enforced throughout the agency for permanent implants is requiring an exhaustive extraction with extractables studies. The science behind this extraction technique is complex. Exhaustive extraction studies involve extracting the device in solvents with a range of polarity, and repeating the extraction until the amount of extractable material in a subsequent extraction is less than 10% by gravimetric analysis of that detected in the initial extraction. The intent of these studies is to determine the cumulative amounts of each chemical that could extract from the device over time.
Once the test articles extract correctly, the agency review of the analytical chemistry report further expects complete chemical identification. At WuXi AppTec, we are regularly working with companies to respond to regulatory questions based on other contract research laboratories’ analytical chemistry reports. Frequently, in order to resolve the regulatory issue, repeating extractables studies is the only approach that will meet the regulatory scrutiny. Why not avoid the submission delay and repeated costs by working with WuXi AppTec from the beginning?
We built our analytical chemistry program knowing that complete chemical identification is necessary and absolute. Without chemical identification, a risk assessment is virtually meaningless. Without complete chemical characterization and risk assessment, a regulatory submission is missing two of three components of biological evaluation as defined by ISO 10993.