At the end of last year, the European Commission launched its consultation to targeted stakeholders on the first full review of Annex 1 of Eudralex volume 4 on the manufacturing of sterile medicinal products.
Annex 1 was first published in 1971 and has been updated a few times since but until now was not put through a full review. The objective of this review is to introduce and clarify principles of quality risk management to incorporate new technologies and innovative processes.
The main anticipated changes are the introduction of new sections covering utilities, environmental and process monitoring, QRM principles, rational restructuring of the Annex and added detail for more precision and clarity.
In order to promote and sustain the global alignment of standards, and achieve and ensure the highest quality medicinal products, the proposed revised version was drafted by the European Commission in collaboration with the World Health Organisation and the Pharmaceutical Inspection Cooperation Scheme.
The manufacture of sterile medicinal products covers a range of different products (from sterile active substances to the finished dosage form), batch sizes (single unit to multiple units), processes (from highly automated systems to manual processes) and primary packaging materials and technologies (such as biotechnology, classical small molecule manufacturing and closed systems).
The Annex ultimately aims to provide guidance for sterile medicinal products
Annex 1 provides general guidance applying to all sterile medicinal products and sterile active substances, through adaptation, using the principles of Quality Risk Management (QRM), to ensure that microbial, particulate and pyrogen contamination associated with microbes is prevented from developing in the final product.
The Annex ultimately aims to provide guidance for sterile medicinal products. However, some of the guidance and principles, such as contamination control strategy, room qualification, classification, monitoring, and gowning may even be used to support the manufacture of other products that need not necessarily be sterile (such as certain liquids, creams, ointments, and low bioburden biological intermediates) but where contamination control is considered important.
The consultation covers products (other than sterile medicinal products) where the general principles of the annex can be applied; general principles applied to the manufacture of medicinal products; Pharmaceutical Quality System (PQS) and the specific requirements of the PQS when applied to sterile medicinal products; requirements for personnel training, qualifications, knowledge, and skills; the design and qualification of premises design including the use of barrier technology; the design and operation of equipment; utilities requirements such as water, air, and vacuum; production technologies such as aseptic and terminal sterilisation processes; different technologies such as lyophilisation and Blow Fill Seal (BFS); sterilisation of products, equipment, and packaging components; environmental and process monitoring; Aseptic Process Simulation; and Quality control (QC).
Considering the potential impact on the pharmaceutical industry and institutional players, the European Commission’s Directorate-General for Health and Food Safety consultation ends on March 20, in parallel with PIC/S (Pharmaceutical Inspection Co-operation Scheme) and the WHO’s public consultation.
Anthia Zammit is licensed to practice law in Malta and New York.
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