European Medicine Agency (EMA) has issued a concept paper on the revision of Annex 15 of the GMP (good manufacturing practice) guide. The start of public consultation has commenced on November 27, 2012 and will end on February 28, 2012.

Annex 15 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 continuous manufacture 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 on this annex is required.

Since Annex 15 was published in 2001 the manufacturing and regulatory environment has changed  significantly and an update is required to this annex to reflect this changed environment. In this regard the preparation of draft concept paper was undertaken in September 2012 meeting. The approval of draft concept paper was received on October 2012 and released for consultation with the industry in November.

Although the current version of Annex 15 refers to the concept of risk assessment, the 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 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, said the regulatory authority.

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 This will include new guidance and also the removal of text that has been superseded or included elsewhere in the GMP Guide. Some of the main GMP changes include implication of Product Quality Reviews on validation activities, new text on change control in Chapter 1 and guidance issued by other regulatory agencies such as WHO and FDA would  be considered during the text 18 revision to align expectations among others.

It is proposed that Annex 15 would be updated to reflect changes in the regulatory and manufacturing  environments. The scope of the project will be limited to Annex 15 but will take into account related 26 changes in other GMP Chapters and Annexes as well as changes in other regulatory documents, said the regulatory authority.

Together with support from the EMA, there will 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  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.