On 10 December 2007, Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on Advanced Therapy Medicinal Products (the ATMP Regulation) and amending Directive 2001/83/EC and Regulation (EC) 726/2004 was published in the Official Journal of the European Union. The ATMP Regulation intends to define and regulate existing and future ATMPs, such as gene therapy, somatic cell therapy and tissue engineered products, intended for the market in Member States, being either prepared industrially or manufactured by a method involving an industrial process.
In particular, the ATMP Regulation, which entered into force the 30 December 2007 and will apply as from 30 December 2008, provides for several new requirements and incentives for:
- specific rules on the authorisation, supervision and pharmacovigilance of ATMPs (i.e. revised technical requirements as to SPC, labelling and package leaflet; new additional post-authorisation requirements as to the follow-up of efficacy/adverse reactions, risk management and traceability);
- an EMEA final evaluation in the case of combined ATMPs;
- special incentives for Small and Medium Enterprises (SMEs) developing ATMPs (i.e. Scientific Advice on the design and conduct of pharmacovigilance and risk management1 ; ii. Scientific Recommendation on ATMP classification 2; iii. Certification of quality and non-clinical data 3; iv. Additional fee reduction for SMEs or hospitals are also available (only during the transitional period referred to in Article 29), provided they can prove there is a particular public health interest in the Community 4.
Notably, manufacturers, companies and hospitals which already have ATMPs on the market (i.e. ATMPs placed on the EU market according with national or EU legislation of 30 December 2008) will also need to comply with the new requirements. In this regard, an application in compliance with Annex I to Directive 2001/83/EC, as amended, and with the Paediatric Regulation will have to be submitted to the EMEA for evaluation (unless the exemption under Article 28(2) of ATMP Regulation applies 5) by 30 December 2011 (for ATMP other than tissue engineered products) and 30 December 2012 (for tissue engineered products) - the so-called transitional period. The review process will then follow the normal procedure for the centralised procedure for ATMPs 6.
It should be noted, however, that the above mentioned deadlines should be considered as already including the time needed for evaluation (i.e. up to a maximum of 210 days’ active review time) and authorisation. Therefore, concerned manufacturers, companies and hospitals should seek regulatory advice as soon as possible in order to discuss the data package to be submitted for this procedure 7.
Finally, it should be noted that as provided in the ATMP Regulation and as part of the Implementation plan agreed between the European Commission and the EMEA, the following documents will be (or were) issued:
- By the EC Commission: i) GCP guidelines (Article 4) ; ii) GMP guidelines (Article 5) ; iii) Amend Annex I to Directive 2001/83/EC (Article 7); iv) Traceability guidelines (Article 15(7)) ; v) Implementing provisions on certification of quality/non-clinical data (Article 18).
- By the EMEA: i) Specific procedures for the evaluation of ATMP (Article 8); ii) Guidelines on Post-authorisation follow up/Risk management (Article 14); iii) CAT’s Rules of Procedure (Article 20 and 21 of ATMPs Regulation and Article 61(8) Regulation (EC) No 726/2004).
1. 90% fee reduction for SMEs and 65% for others (see Article 16 of ATMP Regulation).
2. See Article 17 of ATMP Regulation.
3. See Article 18 of ATMP Regulation, where for the first time a system of evaluation and certification of ATMP quality and, where available, non-clinical safety data is introduced in EU legislation providing a very useful tool for all EU SMEs. The system intends to incentivise the conduct of those studies and aims, in particular, to facilitate the evaluation of any future application for clinical trials and MA applications based on the same data.
4. 50% reduction on MA fees and 50% for post-authorisation activities during 1 year (see article 19 of ATMP Regulation).
5. In line with Regulation (EC) 1394/2007. Please note that for this MA procedure, no fee will need to be paid to the EMEA.
6. ATMP prepared on a non-routine basis according to specific quality standards, and used within the same Member State in a hospital under the exclusive professional responsibility of a medical practitioner, in order to comply with an individual medical prescription for a custom-made product for an individual patient.
7. In particular, please note that for Module 5 of the (e)CTD, the data to be submitted can include information obtained from use of the