Chapter 5 of European Union Good Manufacturing Practice (EU GMP) has been updated and came into operation on 1st March 2015. This post summarises the main changes. The EU GMP Chapter 5 OLD and EU GMP Chapter 5 NEW versions of the chapter can be found by clicking on these links so you can compare the two for yourself.
There are four main areas in which Chapter 5 have been updated, concerning prevention of cross-contamination in production, control and approval of suppliers, testing of incoming materials and notification to the regulatory authority of potential product shortages to the market. Here we will look at each one of these briefly.
Prevention of cross-contamination in production
This section (clauses 5.17 – 5.22) has a substantial amount of additional requirements concerning avoidance of cross-contamination, with numerous mentions of the requirement to evaluate potential risks and act accordingly. There are also extensive details of Technical Measures and Organisational Measures that should be taken to avoid or reduce the chances of cross-contamination. Technical Measures include the use of dedicated facilities, barrier and closed systems and Organisational Measures include dedicating equipment for use on a campaign basis, clothing requirements and cleaning. There is further mention here of the use of dedicated facilities and equipment – see my previous post on the update to Chapter 3 about this. There is certainly more detail here about the use of dedicated and closed systems.
Control and approval of suppliers
This section (5.27 – 5.30) also has some substantial changes. I have always argued that the old chapter was weak here when all it said what that suppliers should be “approved”, with no details on the mechanisms available for such approval and certainly no mention of the word “audit”. Now we get much more detail, including for the first time in EU GMP the need to audit suppliers of the Active Ingredients. It also states that these audits should be of suitable duration and further audits may be needed as necessary. There is also now guidance on the need to control suppliers of excipients, although no formal requirement to audit them. Some are likely to be controlled and monitored more than others, and a risk based approach is indeed suggested.
NOTE – if you are involved in auditing suppliers then do consider this course if you are not a trained auditor. We cover how to perform supplier audits, including the requirements of Active Ingredient GMP and Excipient GMP. You may then also become registered with IRCA as an internationally recognised pharmaceutical auditor.
Testing of incoming materials
This section (5.35 – 5.36) brings in a number of new requirements. It does not cover the detail of how to perform any testing (this being covered by Chapter 6 on Quality Control) but it does give more guidance on the rationale for the number of containers sampled, guidance on the use of Certificates of Analysis (CofAs), another mention of auditing the suppliers and consideration of the distribution of the materials rather than just its manufacture.
NOTE – at some stage I did see an earlier draft version of this chapter and it did state that supplier’s audit reports should be made available for inspection by regulatory inspectors. This has been dropped now, but there is no reason why they are not entitled to view such records.
Notification to the regulatory authority of potential product shortages
This final section (5.71) for the first time introduces the need to alert your Regulatory Authority if you are having issues that may or will restrict the supply of medicines to the market. I guess that this becomes more relevant when there is no alternative product available on the market. Here it is nice to see that the availability of medicines becomes a GMP requirement for the first time.
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
Find out about our course ranges