EU modernizes 14-year old GMP guide on qualification/validation for drug makers
This article was originally published in SRA
The European Commission has updated its 14-year old guidance on good manufacturing practice (GMP) requirements relating to the qualification and validation of facilities, equipment, utilities and processes used for manufacturing medicinal products1.
The revised guideline – which is called EU GMP Annex 15 for Qualification and Validation – will come into effect on 1 October. It will replace the current version of the guidance that has been in effect since July 20012. The commission clarifies that the revised guideline can also be used as supplementary optional guidance for active substances.
The 16-page revised document is much more comprehensive than the current 11-page version, says the European Compliance Academy, an independent membership association that deals with pharmaceutical quality assurance and GMP compliance3. The ECA says that influences from the International Conference on Harmonisation guides ICH Q8 (on pharmaceutical development), Q9 (on quality risk management] and Q10 (on pharmaceutical quality system) can be clearly seen in the revised guideline. This makes the document more modern, and it is more adapted to the current state of science and technology. The ECA however adds that "the (necessary) integration of ICH Q8-Q11 [guidelines] and the lifecycle approach" has also made the new Annex 15 "more vague".
The ECA believes that the revised annex will result in considerable changes in the area of cleaning validation. It notes that "a lot has fortunately been adapted to the current state of technology." However, it adds that "the strong focus on toxicological evaluations as acceptance criteria with regard to existing products will certainly cause uncertainties".
Among other things, the revised guideline includes greater options for process validation. While it is still possible to use the previous traditional approach (where a number of batches of the finished product are manufactured under routine conditions to confirm reproducibility), the ECA says that the possibility of "continuous process verification" and a "hybrid approach" are new concepts in the guideline.
The ECA notes that allowing multiple options for process validation is very different from what is followed in the US, where only one approach – continuous process verification – is allowed. It says that a closer co-ordination with the Food and Drug Administration guideline on process validation "would have been desirable".
The revised guideline also contains updated requirements on the qualification of equipment, facilities, utilities and systems. The qualification process is explained in stages and there is a new requirement to establish user requirements and/or functional specifications at the first stage, followed by design qualification (in the current version of the guideline, design qualification is listed as the first step of the process).
Additional new requirements regarding the qualification process include: the factory acceptance test and the site acceptance test. Especially for equipment with new or complex technology, the guideline states that a factory acceptance test may be conducted. Also, it clarifies that where appropriate and justified, documentation review and some tests performed as part of the factory acceptance test can be incorporated in other steps without repeating them in the installation qualification/operational qualification, the ECA notes.
Also, the revised guideline requires drug companies to include greater information in their validation master plans (eg, information on change control and deviation management for qualification and validation, guidance on developing acceptance criteria, and the qualification and validation strategy, including requalification, where applicable).
In addition, the chapters on transport verification, packaging validation, qualification of utilities and validation of analytical methods are new in the revised guideline.
A draft version of the revised guideline was issued for stakeholder consultation in February last year4.
References
1. EudraLex Volume 4, Annex 15: Qualification and Validation, 30 March 2015, http://ec.europa.eu/health/files/eudralex/vol-4/2015-10_annex15.pdf
2. EudraLex Volume 4, Annex 15: Qualification and Validation, July 2001, http://ec.europa.eu/health/files/eudralex/vol-4/pdfs-en/v4an15_en.pdf
3. ECA news, 2 April 2015, www.gmp-compliance.org/enews_04792_New-EU-GMP-Annex-15-Revision-published---Valid-as-of-1-October-2015.html
4. Feedback sought on 'extensive' revisions to EU qualification/validation GMP for drugs, Scrip Regulatory Affairs, 24 February 2014