Annex 15 qualification and validation was originally published in September 2001, and since then there have been significant changes in the GMP environment with the incorporation of ICH Q9 and Q10. In addition, the Quality Working Party (QWP) is in the process of updating its guideline on Process Validation, and there has been advancement in manufacturing technology through the introduction of Process Analytical Technology (PAT) and the continuous manufacturing concept. There have also been many changes to other Chapters and Annexes in the GMP guide, which may have an impact on Annex 15, and therefore a review of this Annex is required. The draft Concept Paper on revision of Annex 15 of the GMP guide can be found here.
Although the current version of Annex 15 qualification and validation refers to the concept of risk assessment, this activity has been further developed through the introduction of ICH Q9, and further guidance needs to be incorporated into the Annex. The concepts in ICH Q9 together with those in ICH Q8 and Q10 have triggered the revision of QWP’s Guideline on Process Validation, and new guidance needs to be incorporated into Annex 15, including the inclusion of continuous process verification for products subject to an ‘enhanced’ approach to pharmaceutical development. Manufacturing technology has also developed further over the last 10 years in terms of the complexity of equipment, and Annex 15 needs to be updated to ensure that it addresses these changes.
There have also been many changes to GMP and Annex 15 needs to take account of these changes to ensure consistency of requirements. This will include new guidance and also the removal of text that has been superseded or included elsewhere in the GMP Guide. Though not a comprehensive listing, some of the main GMP changes include:
- New text on change control in Chapter 1.
- The implication of Product Quality Reviews on validation activities.
- The work is ongoing to revise the requirements for dedicated facilities in Chapters 3 and 5.
- The revised Annex 11.
Guidance issued by other regulatory agencies such as WHO and US FDA will be considered during the text revision to align expectations as far as possible. Guidance on verifying transport routes and conditions in the supply chain will also be considered in the revision. Further guidance will be added to the sections on documentation and validation types including transfer validation and qualification of equipment.
Together with support from the EMA, there will be a rapporteur from the UK and support from experts in 4 other EU competent authorities (including Ireland, Germany, Italy and Portugal) and from the non-EU 5 PIC/S Participating Authority (Canada). Given the key changes in the corresponding QWP document, there will be close working with members of that drafting group.
The updated Annex is intended to benefit both industry and regulators by incorporating new regulatory concepts, clarifying requirements and taking the opportunity to adopt a common approach with non-EU regulatory authorities. No adverse impact on the industry in terms of resources or costs is foreseen.
The proposed date for the release of the Annex 15 draft guideline will be December 2013, with the expected date for adoption by Committee to be October 2014.
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