The new revision of EudraLex Annex 1 aims to give guidance on the manufacture of sterile drug products. However, it also suggests that some of its principles and guidance could (and perhaps should) be used to support the manufacture of low bioburden biologicals (active pharmaceutical ingredients/drug substance). Manufacturing a low bioburden biologicals drug substance is subject to the requirements to mitigate the risks of viable and non-viable contaminants.
Annex 1 includes a comprehensive list of criteria for designing and operating sterilizing-grade filters. The list includes an expectation that the filtration system is designed for pre- and post-use filter integrity testing (FIT).
While Annex 1 is relatively explicit about FIT requirements for drug product facilities, no clear guidance is available on FIT requirements in drug substance manufacturing.
Our new paper—A risk-based approach to filter integrity testing requirements for biologics drug substance manufacturers—aims to fill that gap with a risk-based, value-driven approach for FIT testing of sterilizing grade filters used to manufacture low bioburden drug substances.
We used a systematic risk assessment tool designed to mitigate product, process, patient, and business risk, and evaluate multiple categories of sterile filtration operations used in a common drug substance manufacturing facility. It illustrates where higher-risk mitigation controls are recommended and where FIT provides little or no value in terms of risk mitigation.
Driving alignment across industry
Our paper also includes a comprehensive decision tree evaluation process to determine which sterilizing-grade filters should undergo integrity testing when used in typical drug substance manufacturing schemes. The goal throughout is to help drive alignment across industry and identify adaptable best practices for FIT.
The findings of this study and the decision tree model were compared to current industry practice through a survey. Strong alignment was evident, suggesting the model could be used by drug substance manufacturers to develop a robust strategy for FIT, which is consistent with regulatory guidance—specifically EudraLex Annexes 1 and 2.
The risk-based approach is recommended to avoid dilution of effort on unnecessary FIT controls and target critical FIT use cases that increase process reliability and patient safety outcomes.
By considering the true value and mitigation provided by each FIT performed, drug substance manufacturing sites can focus limited resources on those areas best positioned to improve process execution, product quality, and patient safety outcomes. For more information, download the paper here and contact Paul Osborne, Global Change Facilitator, at email@example.com