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10 Pharmaceutical Technology ® Quality and Regulatory Sourcebook eBook March 2024 PharmTech.com starlineart - Stock.adobe.com T he revised European Union good manufac- turing practice (EU GMP) Annex 1 guidance document (1), which was published on Aug. 25, 2022 and came into effect on Aug. 25, 2023, is a more detailed and comprehensive guideline that aims to enhance process understanding and incorporate new innovative tools. The updated Annex 1 also takes into account changes in regulatory and manufacturing environments. However, it is important to examine how the requirements for liquid sterilizing grade filtra- tion within the revised Annex 1 align with technolog- ical advancements and contamination control assur- ance. This paper aims to review technology advances in filtration and identify areas that require clarification in the Annex 1 guidelines. Filtration technology review Sterilizing-grade filtration is a widely used method for sterilizing biologics, and it has become increasingly prevalent due to improvements in filter and mem- brane stability, advanced integrity tests, new design and chemistry features, and process validation activi- ties. These advancements have significantly increased the reliability of aseptic processing steps using steril- izing grade filters, necessarily so; as for most biologics, sterile filtration is the only means of sterilization. Modern sterilizing-grade membrane filters are de- signed and built to meet the strict requirements of the biopharmaceutical industry and regulatory au- thorities. These filters have undergone continuous optimization and development, resulting in several important features: • Steam sterilization resistance: Filters can with- stand high temperatures of up to 134 °C, making them suitable for sterilization by in-line steam or autoclaving even for multiple cycles. The tem- perature/differential pressure profile has been established, which suppor ts the appropriate Filtration Clarification Needs in Annex 1 Maik W. Jornitz, principal consultant, BioProcess Resources LLC. Misalignment around liquid filtration requirements and contamination control assurance still persist despite the revisions to Annex 1.