ISO/TC 198/WG 9 - Aseptic processing

This document specifies the requirements for and provides guidance on the specification, selection, qualification, bio-decontamination, validation, operation and control of isolator systems related to aseptic processing of health care products and processing of cell-based health care products. This document does not specify requirements for restricted access barrier systems (RABS). This document does not supersede or replace national regulatory requirements such as Good Manufacturing Practices (GMPs) and/or compendia requirements that pertain in particular to national or regional jurisdictions. This document does not specify requirements for isolators used for sterility testing; however, some of the principles and information in this document could be applicable to this application. This document does not define biosafety containment requirements.

ISO 13408-2:2018 specifies requirements for sterilizing filtration as part of aseptic processing of health care products conducted in accordance with ISO 13408‑1. It also offers guidance to filter users concerning general requirements for set-up, validation and routine operation of a sterilizing filtration process. ISO 13408-2:2018 is not applicable to removal of viruses. Sterilizing filtration is not applicable to fluids that intentionally contain particles larger than the pore size of the filter (e.g. bacterial whole-cell vaccines). ISO 13408-2:2018 is not applicable to high efficiency particulate air (HEPA) filters. ISO 13408-2:2018 does not specify requirements for the development, validation and routine control of a process for removing the causative agents of spongiform encephalopathies such as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease. Specific recommendations have been produced in particular countries for the processing of materials potentially contaminated with these agents.

ISO 13408-7:2012 specifies requirements and provides guidance on alternative approaches to process simulations for the qualification of the aseptic processing of medical devices and combination products that cannot be terminally sterilized and where the process simulation approach according to ISO 13408-1 cannot be applied. ISO 13408-7:2012 describes how risk assessment can be used during the development of an aseptic process to design a process simulation study for medical devices and combination products in those cases where a straightforward substitution of media for product during aseptic processing is not feasible or would not simulate the actual aseptic process.

ISO 13408-1:2008 specifies the general requirements for, and offers guidance on, processes, programmes and procedures for development, validation and routine control of the manufacturing process for aseptically-processed health care products. ISO 13408-1:2008 includes requirements and guidance relative to the overall topic of aseptic processing. Specific requirements and guidance on various specialized processes and methods related to filtration, lyophilization, clean-in place (CIP) technologies, sterilization in place (SIP) and isolator systems are given in other parts of ISO 13408.

ISO 13408-5:2006 specifies the general requirements for sterilization in place (SIP) applied to product contact surfaces of the equipment used in the manufacture of sterile health care products by aseptic processing and offers guidance on qualification, validation, operation and control. ISO 13408-5:2006 applies to processes where sterilizing agents are delivered to the internal surfaces of equipment that can come in contact with the product.

ISO 13408-3:2006 specifies requirements for, and offers guidance on, equipment, processes, programmes and procedures for the control and validation of lyophilization as an aseptic process. It does not address the physical/chemical objectives of a lyophilization process.

ISO 13408-4:2005 specifies the general requirements for clean-in-place (CIP) processes applied to product contact surfaces of equipment used in the manufacture of sterile health care products by aseptic processing and offers guidance on qualification, validation, operation and control. ISO 13408-4:2005 is applicable to processes where cleaning agents are delivered to the internal surfaces of equipment designed to be compatible with CIP, which may come in contact with the product. ISO 13408-4:2005 is not applicable to processes where equipment is dismantled and cleaned in a washer. ISO 13408-4:2005 does not supersede or replace national regulatory requirements, such as Good Manufacturing Practices (GMPs) and/or compendial requirements that pertain to particular national or regional jurisdictions.

ISO 13408-6:2005 specifies the requirements for isolator systems used for aseptic processing and offers guidance on qualification, bio-decontamination, validation, operation and control of isolator systems used for aseptic processing of health care products. ISO 13408-6:2005 is focused on the use of isolator systems to maintain aseptic conditions; this may include applications for hazardous materials. ISO 13408-6:2005 does not supersede or replace national regulatory requirements, such as Good Manufacturing Practices (GMPs) and/or compendial requirements that pertain in particular to national or regional jurisdictions.

ISO 13408-2:2003 specifies requirements for sterilizing filtration as part of aseptic processing of health care products. It also offers guidance to filter users concerning general requirements for set-up, validation and routine operation of a sterilizing filtration process, to be used for aseptic processing of health care products. ISO 13408-2:2003 is not applicable to removal of viruses. Sterilizing filtration is not applicable to fluids containing particles as effective ingredient larger than the pore size of a filter (e.g. bacterial whole-cell vaccines).