environment. But who is actually authorised to initiate and implement new developments and what procedure is followed when a revision is in the making?
The GMP/GDP Inspectors Working Group (GMP/GDP IWG) at the European Medicines Agency (EMA) plays the leading role here. The members of this group are representatives of the GMP supervisory authorities of the EEA member states. They meet on a quarterly basis at the EMA in London, where their activities include updating the EU GMP Guide.
The GMP/GDP IWG has the authority to initiate revision of the GMP Guide. A revision can be triggered by a number of things: a proposal from within the IWG itself, a request from the European Commission (e.g. for implementation of guidelines) or suggestions from the pharmaceutical industry.
The first step within the IWG is to appoint a rapporteur to coordinate matters and usually to write the initial texts. Other members are then selected for what is referred to as the drafting group (between two and six members, depending on the scope of the revision). The members co-author the new, updated document (usually in face-to-face meetings, but also through the exchange of correspondence).
First of all, before the actual revision begins, the drafting group writes a concept paper, which is approved within the GMP/GDP IWG and published by the Commission for a three-month consultation period. The concept paper has a specified structure and its purpose is to present the reasons for the proposed revision and at the same time to outline possible content. This gives the interested public an opportunity to submit suggestions and/or objections, which the drafting group will take into consideration when preparing the documents to be revised.
The drafting group discusses the first drafts of the texts and comes to an agreement internally, within the GMP/GDP IWG. After approval by the IWG the draft is passed on to the Commission and published for consultation (generally for a three-month period). All comments received are published by the Commission. The rapporteur reviews them and either takes them into account in further proceedings or gives the reasons for disregarding them.
The next version of the document in turn is approved by the IWG and forwarded to the Commission. A repeat consultation may follow if there are a very large number of amendments. The Commission performs a final review for legal and sometimes also political aspects. The final version of the document is then published on the Commission website at EudraLex - Volume 4 Good Manufacturing Practice (GMP) Guidelines.
Last year the European Commission closed public consultation on the two chapters and published all comments received. The texts are currently undergoing final processing at the GMP/GDP IWG.
The revision relates primarily to a topic that has long been the subject of intense debate within the industry and the governmental bodies: applying the principles of quality risk management to rule out cross-contamination. That is why setting up regulatory requirements that are equally acceptable to the European member states, the Commission and ideally to manufacturers as well, has been a difficult and tedious process. Publication of the final version is expected in the course of this year.
The Safety Working Party of the EMA in conjunction with the GMP/GDP IWG has developed the Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities. This guideline should be read parallel to the above-given chapters of the Guide. It provides assistance for a toxicological evaluation that is called for as part of the risk assessment. It was placed parallel to the Guide chapters for public comment in 2013 and is slated for concurrent publication of the final version.
On 3rd April 2014 the European Commission published a revised version that will go into effect on 1st October 2014. The new version will then replace that of 2005, which is presently still in force.
New developments relate in particular to requirements for the transfer of methodology, but requirements for laboratory reactants, media, etc. have also been modified.
Public consultation and publication of the comments were concluded last year. The text is currently undergoing final processing at the GMP/GDP IWG.
Quality risk management is now routinely applied when quality defects or complaints are being investigated and decisions on product recalls are made. The important thing is also to take the causes of the defect into consideration and to take appropriate preventive actions in order to guard against a recurrence. Added clarification is provided concerning when the authorities must be notified about quality defects and complaints.
The European Commission published a draft revision of Annex 15 on 06 February 2014. The draft is open for comments until 31 May 2014. The document is scheduled for approval by the Commission in October of 2014. Considering the large number of amendments and the brisk need among supervisory authorities to debate the issue and come to an agreement, and in light of the many anticipated comments from industry, it may be assumed that the new Annex will not be published until 2015.
Annex 15 has been in force since 2001, which is why it is in dire need of being updated and adapted to regulations and technical developments that have arisen in the meantime. The draft emphasises those chapters of Part I of the GMP Guide that have recently been updated, as well as Annex 11 on computerised systems. As anticipated, the principles of ICH Q8, Q9, Q10 and Q11 have also been addressed.
The draft revised version of Annex 16 was open for public consultation until the end of November 2013. The rapporteur of the GMP/GDP IWG (the Finnish regulatory agency FIMEA) is in the process of reviewing comments received and developing a consolidated version together with the drafting group. Publication of the final version will foreseeably take place in the course of this year.
Annex 16 now takes the global supply chain into account and deals with implementation of new control strategies for quality. Of primary importance here are detailed requirements for the Qualified Person (QP), reliance on third-party GMP verification and handling unplanned deviations.
Draft revisions of Chapters 3, 5 and 8 of the EU GMP Guide:
Draft SWP Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities:
New Chapter 6 of the EU-GMP Guide:
LOGFILE No. 13/2014 – EU-GMP Guide Quality Control, feature article:
Draft of Annex 15:
Dr. Sabine Paris
Maas & Peither AG, GMP Publishing