The title of the chapter has changed from “Quality Management” to “Pharmaceutical Quality System”. For your reference both OLD and NEW versions can be seen here: Chapter 1 Quality Management OLD and Chapter 1 Pharmaceutical Quality System NEW
The document takes a number of key elements from ICH Q10 on “Pharmaceutical Quality Systems” and cross-references this a number of times. Note – ICH Q10 was planned to become a new Annex 21 of EU GMP but for some unknown reason this has been moved (along with the Annex 20 on Risk Management) to a new Part 3 of GMP. If any Regulators are reading this – please let us know why this has been done! It’s very confusing and I think that moving it is a backward step in promoting evolution of pharmaceutical quality management thinking! (I just had to get that off my chest).
No major change, except updated to cover the fact that you must comply (when applicable) to your Clinical Trial Authorisation instead of Marketing Authorisation for Clinical Trial Materials. Of note as well is that Senior Management is still mentioned in this section, but historically this was the only mention of Senior Management in EU GMP. They are now mentioned a further three times in the new chapter – giving a greater emphasis on Senior Management having an active involvement in their Quality Management System.
Pharmaceutical Quality System (Clauses 1.1 – 1.7): This is the major change in this chapter and will be covered more shortly.
Good Manufacturing Practice (1.8 ): No major change.
Quality Control (1.9): No major change.
Product Quality Review (1.10 – 1.11): No major change.
Quality Risk Management (1.12 – 1.13): No major change.
Pharmaceutical Quality System (Clauses 1.1 – 1.7):
Returning to this section, this is where the major changes are. Most of the requirements of what was stated in the previous Chapter’s requirements for “Quality Assurance” have been kept, but in these 6 new clauses there is greater depth of coverage of what a Pharmaceutical Quality Management System is. The major changes include:
- Enhancing the importance of considering GMP not only at the manufacturing stage but also during development, technology transfer and product discontinuation (clause 1.2). This follows the spirit of ICH Q10.
- The first mention of continual improvement of the system (clause 1.2). Traditionally GMP has not been an active promoter of continual improvement – now it is!
- A greater emphasis of process knowledge (1.4 ii), process performance (1.4 viii) and process monitoring (1.4 ix). This is in line with ISO 9001 principles – which have a strong emphasis of monitoring and improving all processes of the Quality Management System.
- A stronger emphasis on control of suppliers, the supply chain and all outsourced activities (1.4 vi and vii). This is in line with the regulators concern over the whole supply chain.
- Another mention of continual improvement (1.4 xii) can also be seen.
- Improved coverage of evaluation of changes both before they are taken and afterwards (1.4 xiii and xiv). Note – there is still no real depth of coverage of a “Change Control System” in EU GMP yet all firms have Change Control Systems.
- The first mention of Root-Cause Analysis following problems (1.4 xv). In this section you also see the first mention in EU GMP of Human Error and CAPA. These three terms have never been mentioned in EU GMP before.
- An enhanced role for Senior Management (1.5). Here you see that Senior Management (and not the QA Manager) are responsible for the QMS as well as defining roles and responsibilities and ensuring these are defined, communicated and implemented throughout the organisation. Of note is that this is the first mention of “communication” in EU GMP and a strong suggestion that the QMS extends to the whole organisation, and not just the GMP areas.
- The formal arrival of Management Review (1.6). This is another ISO 9001 principle with Senior Management required to perform regular review of their quality systems, including identification of improvement of products, processes and the whole system.
- Finally a Quality Manual is required (1.7). This is also covered in the recently updated EU GMP Chapter 4 on Documentation. Here we get more detail of what is expected within a Quality Manual. This again is an ISO 9001 idea and in this case should include a description of the quality management system as well as management responsibilities. In ISO 9001 this description of the QMS is achieved by describing the processes of the QMS, its scope and the documents that form the QMS.
I hope that this overview and my thoughts and comments are of interest. As you can see this new chapter see an evolution of quality management thinking in line which what is common in other industries. We still have a fair way to go – but it is a movement in the right direction. Feel free to comment as usual.
If you want to know more about how to audit and improve a Pharmaceutical Quality Management System then look at our Pharmaceutical Quality Management System Lead Auditor course for more information on our website.
Annex 1 has finally arrived, 25th Aug 2022 saw the publication of Annex 1. Normally, updates to GMP chapters and Annexes have a 6-month lead time for implementation. In the case of the new Annex 1, the lead time is 12 months, except for clause 8.123 relating to lyophilization which has 24 months lead time.
Annex 1 was first issued in 1971 as the only annex in the first ever UK guide to Good Manufacturing Practice. Since then, there have been several updates but not full revisions. In 2012 there was a proposal to revise Annex 1 with a re-proposal in 2014 by the UK’s MHRA. At the time, a full rewrite was considered unlikely and instead the intention was to provide a document that would confirm regulatory expectation and as such, not place any new requirements or costs on the pharmaceutical industry.
While this principle, is still upheld, it was clear from the first draft for public comment of December 2017, that a rewrite was being undertaken. The first draft created around 6200 comments coming from regulatory organizations, such as the pharmaceutical cooperation scheme, regulatory bodies outside of the EU, support organizations such as the Parenteral Drug Association, the Parenteral and Healthcare Sciences Society, the Pharmaceutical Microbiology Interest group as well as representatives from the manufacturers within the pharmaceutical industry to name just a few. Rarely do updates require a second public consultation but in the case of the annex 1 update a second draft was issued in March 2020 although this was a more targeted review in terms of the sections and clauses that comment was being sought for.
About the author
Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.
Training courses on Annex 1
There are a number of half-day workshops organised to take you through the changes in more detail and to look at how they relate to your organisation.
Our 2-day course is updated for Annex 1 changes
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