Submission of comments on Revision of ‘Annex 1: Manufacture of
Sterile Medicinal Products’
Jim Agalloco, Russ Madsen and Jim Akers developed a comprehensive set of comments to the draft revision of Annex 1.
The authors believe it is essential that the EMA receive comments that outline the difficulties that the draft presents. Their more than 170 comments cover the entire document and detail its many shortcomings. Feel free to download and reuse them in your own comment submission on EMA’s December 2017 revision.
Keywords: Submission of comments on Revision of ‘Annex 1: Manufacture of Sterile Medicinal Products’
1. General comment: The document is inconsistent in its use of references, they are present in some sections and absent in others. The document should include a comprehensive set of reference documents to support the points made in the text. This is especially important for those aspects of the draft that are most contentious.
2. General Comment: The document presents a view of sterile product manufacture inconsistent with that developed elsewhere as codified in regulations, international standards and pharmaceutical compendia. For example, U.S. and Japanese guidance on sterile product manufacturing differ markedly from what is presented. The cleanroom content in the draft does not conform to ISO 14644 and perpetuates the myths that clean rooms can be classified microbiologically and that microbiological testing can enhance sterility assurance. USP chapters <1211>, <1228> and <1229> provide more contemporary and appropriate guidance for sterile product preparation. There are also conflicts with current EMA guidance, e.g., the WFI Q&A paper and Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products.
3. General Comment: Provide separate consideration of conventional cleanrooms, RABS and isolators because they are demonstratively different in many ways and considering them together denigrates isolator performance, elevates RABS capabilities and does not adequately consider the contamination risk in the far less capable barrier equipped conventional cleanroom.
Specific comments on text
13-14. Comment: The statement lacks definition and direction because it doesn’t point to the more
important aspect of QRM in relation to sterile product manufacture which is Risk Mitigation.
Assessment of risk is not enough: the document should explicitly support risk mitigation.
Additionally, for consistency with that expectation, there should be no ‘requirements’ included in
the document that potentially increase the risk of microbial, or particulate contamination of
Proposed change: … using the principles of Quality Risk Management (QRM)) with emphasis on mitigation of risk at all times, …
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