IMPs: Responses to the public consultations on new GMP Regulations published

Last year, the EU Commission has published four public consultations on investigational medicinal products (IMPs) concerning both good manufacturing practices (GMP) and clinical trials (GCP) for human medicinal products:

• Commission Delegated Act on principles and guidelines on good manufacturing practices for investigational medicinal products for human use and inspection procedures
• Detailed Commission guidelines on good manufacturing practices for investigational medicinal products
• Commission Implementing Act on principles and guidelines on good manufacturing practice for medicinal products for human use
• Detailed arrangement for clinical trials inspection procedures including the qualifications and training requirements for inspectors

The reason was that once Regulation (EU) No 536/2014 on clinical trials becomes applicable, manufacture and import of IMPs for the use in clinical trials carried out under that Regulation cannot follow GMP for IMPs set out in Directive 2003/94/EC. They then have to be manufactured or imported under regulations laid down by the Delegated Act or other specified regulation.

Stakeholders were invited to provide their views on the requirements for the principles and guidelines of GMP and the detailed arrangements for inspection for ensuring the quality of investigational medicinal products and to answer some questions. A summary of the answers can be found in a summary document.

Amongst the 26 feedback providers, the IMP Working Group of the European QP Association also gave feedback to the Commission Delegated Act on Principles and guidelines on GMP for IMPs for human use and inspection procedures and to the Detailed Commission guidelines on GMP for IMPs for human use. The IMP Working Group within the European QP Association very much appreciates the ongoing revision of GMP guidelines for Investigational Medicinal Products for human use in the context of implementation of the Clinical Trial regulation.

In general the Working Group would like to recommend that the requirements for IMPs and commercial MPs as set forth in revised Annex 16 should be clearly delineated. e.g. by introducing clear guidance on the supply chain documentation. They also recommend to put more particular emphasis on the quality assurance of IRT systems used by the sponsors and to use a harmonised and consistent use of the terminology throughout the relevant IMP guidance. Also quite a few changes to the wording was proposed with a respective rationale.

The main comments and remarks of the responses of the other organisations were made on the following topics:

• Request for clear definition and interface of manufacturer and sponsor responsibilities, inclusion of the "importer";
• Concerns of potential duplication of already existing GMP requirements;
• Aspects around the conformity of third country manufacturer and products (GMP standards equivalent to EU, QP declaration of equivalence);
• Documentation of any kind of GMP relevant activities and handling of electronic data storage;
• The need for validation of manufacturing processes;
• Request for definitions of retention and reference samples, testing of samples after end of shelf life;
• Harmonised retention period for starting materials;
• Possibility of transitional Qualified Person (QP) and further elaboration on responsibilities of QP;
• Complaint handling process: communication obligations of manufacturer when product defects occur, e.g. defined responsibilities for rapid unblinding;
• Elaborating on specific aspects for advanced therapy investigational medicinal products (self-inspection, reconstitution);
• Supervision by inspections (also on the approach for investigational medicinal products manufactured in third countries), sharing of inspection reports, inspectors' empowerment/ competences/obligations.