Support for advanced-therapy developers

Developers of advanced therapy medicinal products (ATMPs) must be aware of the legislation governing different stages of the medicine development process, including good manufacturing practice (GMP), good clinical practice (GCP) and good laboratory practice (GLP) requirements. The European Medicines Agency (EMA) offers a range of advisory services and incentives to support the development of ATMPs.

EMA provides formal support to developers through:

• Scientific advice and protocol assistance;
• Orphan designation;
• the micro, small and medium-sized enterprise (SME) office;
• Classification of advanced therapy medicinal products (ATMPs);
• Certification of quality and non-clinical data for SMEs.

The legislation provides for scientific and financial incentives to encourage research and development in the area of advanced therapies. Developers of ATMPs can obtain reductions in the fees payable to EMA of:

• 65% fee reduction for a request for scientific advice for ATMPs (90% for SMEs);
• 90% fee reduction for the certification procedure.

The Innovation Task Force provides a forum for informal dialogue between EMA and developers of ATMPs in the early stages of the medicine development process. Registered SMEs may approach the SME office to request a briefing meeting to discuss their planned regulatory strategy.

Information on how to apply for SME incentives are detailed under SME office.

GMP requirements

Developers of ATMPs need to be aware of the legislation that is applicable to different stages of the process.

Utilisation of substances of human origin such as blood, tissues and cells in the manufacture of an ATMP requires compliance with relevant legislation (Directive 2002/98/EC and associated implementing directives and Directive 2004/23/EC and associated implementing directives) in relation to procurement, donation and testing.

Subsequent manufacture of ATMPs must be performed in compliance with Directive 2001/83/EC and in line with the GMP guidelines.

The European Commission has published a set of GMP guidelines specific to ATMPs:

• Guidelines on GMP specific to ATMPs

These guidelines adapt the EU GMP requirements to the specific characteristics of ATMPs and and address the novel and complex manufacturing scenarios utilised for these products. They foster a risk-based approach to the manufacture and testing of such products.

The Agency's Committee for Advanced Therapies (CAT) and GMDP Inspectors Working Group provided extensive input to the development of the guidelines.

The following annexes of the EU GMP guidelines are also important for ATMP manufacturing:

• Annex 2 - Manufacture of biological active substances and medicinal products for human use;
• Annex 13 - Manufacture of investigational medicinal products;
• Annex 16 - Certification by a qualified person and batch release.

Update: EMA’s CAT, together with the GMDP Inspectors Working Group and the Biologics Working Party, have prepared the following questions-and answers-documents: Questions and answers on the exemption from batch controls carried out on ATMPs imported into the European Union from a third country Questions and answers on the use of out-of-specification batches of authorised cell and tissue-based advanced therapy medicinal products Questions and answers on the principles of GMP for the manufacturing of starting materials of biological origin used to transfer genetic material for the manufacturing of ATMPs

GCP requirements

Detailed guidance on specific GCP requirements for ATMPs is available from the European Commission:

• Detailed draft guidelines on GCP specific to ATMPs

These draft guidelines supplement Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for GCP as regards investigational medicinal products for human use.

GLP requirements

CAT in collaboration with the European Commission and the Clinical Trial Facilitation Group has developed a question and answer document on the GLP principles to be taken into account in relation to ATMPs:

• Good Laboratory Practice (GLP) principles in relation to advanced therapy medicinal products (ATMPs)