Standardized Extractables Testing Protocol for Single-Use Systems in Biomanufacturing

G eneral requirements for Extractables and Leachables (E&L) are already mandated by regulatory agencies. Biopharmaceutical companies must meet these requirements in demonstrating equipment suitability and GMP compliance whether the equipment is of traditional design or single-use. However, because of the absence of specific regulatory requirements for extractables testing of SingleUse Systems (SUS) components, companies have needed to generate SUS extractables testing methods by extrapolating from their interpretation of regulatory requirements for existing container closure testing methods. Extractables testing studies conducted by suppliers of SUS for biomanufacturing comprise filling or soaking SUS components in model solvents, and testing the resultant extracts for compounds that were released to the solvent by the treatment. Exposure times and temperature ranges are extended to exaggerate the chemical conditions of actual use. However, there are currently no industry standards for such studies, and while solvents used are often more aggressive than what is typical in biomanufacturing, the full range of conditions encountered by SUS components in actual use is not always represented. In addition, this lack of standardization in extractables testing creates difficulties for end-users in interpreting and comparing test data from different SUS suppliers. Extractables testing study data provided by SUS suppliers must be well documented, reproducible, and readily interpretable in order for biopharmaceutical companies to use a scientific and risk-based approach in determining the readiness of various submissions to regulatory agencies. Current regulatory guidance requires that biopharmaceutical manufacturers ensure the manufacturing systems do not adulterate the final drug product. The end users have used SUS extractables testing data and leachables evaluation to assess potential risks to patients of the use of these components in product manufacturing. If extractables testing data provided by an SUS supplier are not sufficient to perform adequate assessment of risks, it is the time-consuming process for the biopharmaceutical company to conduct their own studies to generate sufficient extractables testing data. This results in the same components being tested multiple times and delay in applications of SUS in biomanufacturing. For a biopharmaceutical company to move a new drug molecule candidate through the clinical development process, the company first develops a position on the drug candidate that will be presented to regulatory agencies for concurrence. This position is applied to successive stages of the clinical development process, culminating in final process validation for commercial manufacturing and licensure. Regulatory guidance for Process Validation outlines three distinct stages: process design, process qualification, and process verification. Equipment design data for bioprocessing components, whether of traditional or single-use design, is required at each stage. Extractables testing is a key Reprinted from PHARMACEUTICAL ENGINEERING THE OFFICIAL TECHNICAL MAGAZINE OF ISPE