For course details click on the subject areas shown in menu below. To contact us: +44 1635 866699

New EU GMP Directive published

The European Union recently published its new Directive for pharmaceutical manufacturing sites that will replace the existing Directive (Directive 2003/94/EC) for human medicines.  The new EU GMP Directive, Commission Directive (EU) 2017/1572, was issued on 15th September 2017 and is to become law by 31st March 2018.  You can see both current and new Directives here – Directive 2003/94/EC and Directive EU 2017_1572.

The new EU GMP Directive removes all aspects of the manufacture of Investigational Medicinal Products (Clinical Trial materials).  This will be subject to separate legislation, namely Regulation 2017/1569.  In one way, this should make the finished product Directive easier to read, and in that respect, it does.  The new Directive has an almost identical structure to the existing one, with many of the requirements exactly the same for finished product manufacturing sites. Based on an initial look at the new Directive, here are a few comments.

Article 3 – Inspection

This article gives a manufacturing site’s Regulatory Authority the right to inspect it.  So there is no major change here, other than a new mention of specific requirements for manufacturers of Advanced Therapy Medicinal Products.There is though a new requirement added for the Regulatory Authorities themselves, as they now must have a “properly designed quality system that shall be complied with by inspectorates’ personnel and management”.  In other words, the inspectors must work within a formal quality system themselves.

Article 13 – Complaints and product recall

The title of the Article reverts back to what is used to be.  When Directive 2003/94/EC was updated the Article was enhanced to cover “Complaints, product recall and emergency unblinding”.  As emergency unblinding is related to Investigational Medicinal Products, then it is logical that this part of the Article should be removed.  However, they have missed a trick here, as the corresponding Chapter of EU GMP (Chapter 8) was updated in March 2015 and is called “Complaints, Quality Defects and Product Recalls”.  The Quality Defects aspect of the Chapter goes into much more detail with regards to Root-Cause Analysis, CAPAs, Investigation and Decision-making, yet none of this is mentioned in the Article itself.  This is a shame I think.

Article 15 – Labelling

This Article covered the packaging and labelling of Investigational Medicinal Products (IMPs) and so logically needed to be removed, which it has been.

Wording – “The Member States shall ensure that …”

A number of the Articles have a subtle change of wording that is not consistent throughout the document.  In the current Directive (2003/94/EC) it always uses the words “The manufacturer shall … ” and this is fine as the Directive is aimed at Manufacturing Sites.  However in this new EU GMP Directive, we see this changed in Articles 4, 5, 6, 8 and 10 to “The Member States shall ensure that the manufacturer shall …”, whereas other Articles, such as Articles 7, 9 and 11, remain as they were (i.e. the words “The manufacturer shall … ”).  I might be being pedantic here, but I think that this wording, coupled with lack of consistency, makes the document less easy to read.

I hope this quick overview is of interest.  If you have any thoughts or comments, then just let us know.

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 Martin

Andy Martin

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

Related Articles

Find out about our course ranges

GMP Training


QMS Training


GDP/RP Training


GMP Compliance


QP Training


GDP Compliance


Free Taster courses

To try a free taster of our online courses to see if they are of interest visit this page.