By August 25th, 2023, manufacturers of sterile medicinal products must comply with the revised EudraLex Volume 4, Annex 1, except for point 8.123 (lyophilizer loading - the deadline here is 25 August 2024). Manufacturers should complete a comprehensive review of all changes in the Annex 1 guideline, which has grown to 52 pages, compared to just 16 pages in the 2008 version.
The Importance of Compliance for Pharmaceutical Manufacturers
The new EU GMP Annex 1 ‘Manufacture of Sterile Medicinal Products’ includes several key changes and updates that the pharmaceutical industry needs to be aware of. These include the adoption of a risk-based approach to process validation, the requirement for a Contamination Control Strategy (CCS), and increased emphasis on environmental monitoring and control.
The revised Annex 1 also places greater emphasis on the role of the Qualified Person (QP) in ensuring compliance and quality assurance. QPs are expected to have a thorough understanding of the principles and requirements of Annex 1, as well as the ability to implement effective quality control measures and risk management strategies.
To ensure compliance with the new EU GMP Annex 1, pharmaceutical manufacturers must be proactive in updating their manufacturing processes and quality systems. This may involve the adoption of new technologies and procedures, as well as the implementation of training programs for staff and regular audits and inspections to ensure ongoing compliance.
Examples of updated requirements
The revised Annex 1 provides detailed guidance on various aspects such as premises, equipment, utilities, personnel, production and technologies, viable and non-viable environmental monitoring, and aseptic process simulation. The new document has expanded to 52 pages, a significant increase from the 16 pages in the 2008 version. Each chapter emphasizes the importance of implementing QRM principles. Some of the updated requirements in the document include:
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Environmental monitoring: The revised Annex 1 requires that manufacturers establish and maintain a robust environmental monitoring program. This includes the use of both non-viable and viable monitoring methods to detect and control microbiological contamination in the manufacturing facility.
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Aseptic process simulation: The updated Annex 1 provides more extensive guidance on the risk-based development and performance of aseptic processing simulation (APS). Manufacturers must conduct a sufficient number of successful consecutive APS to revalidate the process, and any contaminated unit must result in a failed process simulation and require investigation.
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Personnel: Compared to the 2008 version, the updated Annex 1 places more emphasis on the importance of personnel behaviour, hygiene, training, qualification, and disqualification. Manufacturers must validate the maximum number of operators in a cleanroom and qualify the cleanroom garment cleaning process.
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Water for injection: The revised Annex 1 gives detailed guidance on the production of Water for Injection (WFI). The document now allows the production of WFI by methods other than distillation, provided that further techniques such as nanofiltration, ultra-filtration, and electrodeionization are considered in conjunction with reverse osmosis membranes.
Need help implementing a Contamination Control Strategy?
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