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.