Raw Materials Quality: Requirements, Limitations, and Recommendations (from an Ancillary Material Manufacturer’s Perspective) (On-Demand)

Course Description:
As Ancillary Materials (AM) supplier of cytokines and media we are reflecting on current requirements for AM quality systems and limitations we observed and propose recommendations. Requirements Documents with different regulatory status and scope have been developed (e.g. USP chapter <1043> or Ph Eur general chapter 5.2.12, various guidelines on sterile manufacturing and viral safety). Specific AM chapters (e.g. USP <92>) and Technical Standard (ISO 20399) have also been published. Beyond their own quality standards (e.g. ISO quality management system certification), AM manufacturers are expected to support CGT manufacturers with the requirements with regards to AM and AM vendor qualification. Limitations USP <92> addresses quality (of growth factors and cytokines) but only at the analytical level. However, it doesnot address manufacturing and quality assurance system. Indeed, most guidelines are not specifically addressed to AM manufacturers and we experience an increasing variability of health agencies requirements (country- or evaluator-dependent). USP <1043> requires CGT manufacturers to qualify AM. However, while identity and purity are easily defined for some products, they are more complex for others (e.g. cell culture media). This technical issue can make incoming materials identity tests complex. The evaluation of safety can be challenging as the lack of transparency on the use of AM by manufacturers forces AM manufacturer to comply with requirements based on assumptions. On the other hand, the protection of proprietary AM manufacturer data (despite Confidentiality Agreements) limits information exchange that may be critical for safety evaluation. Finally, the CGT manufacturer is required to assess AM overall suitability. AM manufacturers can support their clients but are forced to make assumptions on the use of their products (e.g. functionality tests for cell culture media or stability studies under conditions relevant for the CGT manufacturer). Recommendations Harmonization of health authorities’ expectations could help, in addition to developing further guidelines dedicated to AM and AM manufacturers. Drug Master Files (DMF) can be referred to in case of confidentiality issues, but they are limited to some countries and limited by scope (only evaluated in case of reference to a regulatory submission). An internationally recognized quality standard and certification of compliance for the AM would be useful for both AM manufacturers and CGT manufacturers. AM manufacturing sites cannot be certified GMP-compliant by health authority inspectors. ISO certification (ISO 9001:2015) helps but is still not sufficient to cover all topics relevant for the safety and efficacy of the AM. The possibility for a third party (health authority or inspection body) to carry out inspections covering all relevant cGMP aspects would be welcome. Conclusion: Today, ancillary materials quality