The EU GMP Guide is now updated with a finalized Annex 15, Qualification and Validation. The draft was published for consultation in February, 2014 after a concept paper published in November 2012. Requirements in the final version become effective October 1, 2015. The 16-page final annex is substantially longer than the existing 11-page version, and includes a few changes from the draft version. [NOTE added April 13: PIC/S also published a revised Annex 15, also effective October 1, 2015.] HERE I provide a copy that highlights the changes that appear in the updated Annex 15 that were not in the draft, excluding changes in the glossary. Where there were simple changes in wording, in format, or combination of items I did not mark these as changes. Briefly, the features of the revised Annex 15, when compared to the draft version, that I feel are interesting or relevant are as follows:
- The Principle section indicates this may be used as “supplementary optional guidance for active substances…” with no additional explanation.
- Retrospective validation is no longer considered an acceptable approach, the annex states this several times.
- Section 1.8 calls for maintaining the integrity of data from qualification and validation activities.
- Section 5.1 states that “It is implicit in this annex that a robust product development process is in place to enable successful process validation.” This suggests that inadequate product development processes cannot lead to a successful validation exercise.
- Section 5.28 states that ongoing process verification during the lifecycle is applicable to all validation approaches, traditional, continuous and hybrid.
- Section 10.6 addressing cleaning validation includes a footnote to the EMA guideline on setting health based exposure limits for medicinal products made in shared facilities. Section 10.6.1 addresses that a tox evaluation may not be applicable for macromolecules or peptides that are known to degrade or denature when exposed to extremes of pH and/or temperature. Section 10.6.2 states that where specific product residues cannot be evaluated, other attributes such as TOC and conductivity may be used.
- Section 10.14 references Chapters 3 and 5 in the EU GMP Guideline where cleaning processes may be ineffective for some equipment. Both are revised Chapters that became effective March 1, 2015.
- Section 10.15 addresses the need to confirm the effectiveness of a manual cleaning process at appropriate intervals.
For those who wish to compare with the FDA Guidance on process validation published in 2011, please find that at the link. Both are heavily focused on the lifecycle approach though differences do remain between the two.