2/3 February 2021
In February 2015 the European Commission published a Concept Paper with the intent to revise the EU GMP Annex 1 on sterile manufacturing. The time frame provided by the EU Commission is very small. End of March 2015 has been set as deadline for industry comments and in October 2015 a draft version of the revised EU GMP Annex 1 is planned to be published.
The ECA Foundation and its Interest Group, the European QP Association (EQPA), are Europe´s leading interest Groups in the area of pharmaceutical Quality Assurance and GMP Compliance. Because of the importance of the document ECA and EQPA decided to form an expert working group with members from different pharmaceutical companies and independent experts under the leadership of ECA´s Chairman Richard M. Bonner. Although the time frame provided was very small the ECA /EQPA managed to summarize the feedback provided by the expert group members by 31 March 2015.
The ECA/EQPA Expert Working Group generally welcomes the intention of the EU Commission to revise the EU GMP Annex 1. Since the current version was published in 2008 a number of new technologies have been implemented and challenges have been observed which should be reflected in the revision process. Isolator Technology and especially RABS systems have been introduced in various technical versions in many companies. Currently there is no definition what requirements RABS systems should fulfill, and there is no exact definition for a RABS system either. One of many other topics refers to more details on airlocks (e.g. is it possible to skip one grade between material/equipment airlocks?). It might also be useful to add at least the two new classes E and F.
Harmonisation of standards is an important goal for a revised Annex 1 as well. The requirements laid down in ISO 14644-1 (ISO5) should be considered, e.g. when it comes to monitoring performed for 0.5 µm particles. In addition, changing the 5.0 micron particle limit for grade A to align with ISO 5 (29/m3) might be considered in a new Annex 1. Harmonisation should also be made with the FDA Aseptic Guide to allow companies to meet the same requirements.
The EU Commission announced in their Concept Paper on the revision of Annex 1 that Quality Risk Management (ICH Q9) should be applied. A potential application is the monitoring program. A Monitoring program in classified areas in general, not only Grade C or D, should be performed in accordance with Quality risk management. Other concepts like investigations, sanitisation, etc. should reflect this concept.
One of the most intensively discussed requirements in the current Annex 1 is the wording "Grade A air supply". According to the current EU GMP Annex 1 "stoppered vials should be protected with a Grade A air supply until the cap has been crimped." However, Grade A air supply is not defined and clarification is necessary in the new version.
Many other aspects have been summarised by the ECA/EQPA Expert Working Group. Once the EU Commission will publish the comments we will provide a link to the detailed comments on the ECA webpage.