Scientific progress in the field of cellular and molecular biotechnology has allowed the development of numerous Advanced Therapy Medicinal Products (ATMPs), offering new and innovative treatment opportunities. ATMPs are biological medicines which are classified into four main groups:
- Gene therapy medicinal products: they contain or consist of a recombinant nucleic acid capable of inducing a therapeutic, prophylactic or diagnostic effect. Gene therapy drugs permit to adjust, repair, replace, add or delete a genetic sequence. In the case of genetic diseases in which a gene is defective or absent, gene therapy allows to transfer the working copy of the gene in question.
- Somatic cell therapy medicinal products: they contain or consist of cells or tissues which have been significantly manipulated to modify their biological characteristics, physiological functions or structural properties or which are not intended to be used for the same original functions in the body. The purpose of somatic cell therapy is to treat, prevent or diagnose diseases. The cells or tissues can be of autologous origin (derived from the patient himself), allogeneic (obtained from a donor) or xenogenic (derived from a donor of an animal species other than man).
- Tissue engineered medicinal products: they contain cells or tissues that have undergone significant manipulation or are not intended to be used for the same original functions in the body, with the aim of repairing, regenerating or replacing human tissues.
- Medicinal products for combined advanced therapies: they contain one or more medical devices as an integral part of the medicinal product containing cells or tissues.
Main reference legislation
EC Regulation 1394/2007 is the reference regulatory context for ATMPs, amending in this regard EC Directive 2001/83, Community code relating to medicinal products for human use, and the EC Regulation 726/2004 which establishes Community procedures for the authorization and surveillance of medicinal products for human and veterinary use, and establishing the European Medicines Agency (EMA) https://www.ema.europa.eu/en.
In addition, Directive 2009/120/EC (amending Directive 2001/83/EC) has updated the definitions and scientific and technical requirements for gene therapy and somatic cell therapy medicines. It also established detailed scientific and technical requirements for tissue engineered medicines, as well as for ATMPs containing medical devices.
As for any medicinal product, the development of ATMPs must also comply with Directive 2001/20/EC relating to the application of good clinical practice in conducting clinical trials of medicinal products for human use (Regulation 536/2014) which provides for specific rules for this type of medicines, precisely in consideration of their complexity.
The marketing authorization of ATMPs is mandatory through the centralized marketing authorization procedure. Although the process and timing of the technical-scientific evaluation of the documentation submitted by the pharmaceutical companies remain the same, the role of the Committee for Medicinal Products for Human Use (CHMP) is supported by the Committee for Advanced Therapies (CAT).
The complexity of the ATMPs requires specific skills and the evaluation criteria sometimes go beyond those applied to the traditional pharmaceutical sector, taking into account the rapid development of scientific knowledge. For these reasons, the Committee for Advanced Therapies (CAT) has been set up within the EMA https://www.ema.europa.eu/en/committees/committee-advanced-therapies-cat.
The CAT was established in accordance with the EC Regulation 1394/2007 concerning ATMPs. It is a multidisciplinary committee that brings together the best European experts in the field of advanced therapies. In addition to representatives of each Member State, members of the CHMP are also members of the CAT, along with and representatives of the medical profession and of patient associations with experience in the field.
The main responsibility of the CAT is to prepare a draft opinion drawn up by two Member States (CAT (Co-) Rapporteur) on each application for a marketing authorization of an ATMP, to be submitted to the CHMP for the adoption of the final opinion on the medicinal product in question.
Other responsibilities of the CAT are described below:
- Providing scientific recommendations on ATMPs classification, to determine whether or not a medicinal product under development is an advanced therapy product. For more details on procedural aspects and classification criteria, please refer to the procedural advice and to the reflection paper on the classification of advanced therapy medicinal products. The classification assessment reports are available on the EMA website.
- Evaluating requests for non-clinical quality data certification, for small/medium-sized businesses only. This procedure aims to identify any critical issues before submitting the application for marketing authorization. In case of positive evaluation, a certificate is issued.
- Providing scientific advice on ATMPS in collaboration with EMA's Scientific Advice Working Party (SAWP). This procedure allows to receive a formal opinion on the quality, efficacy, safety and/or post-authorization aspects of an ATMP, based on commercial standards.
- Providing advice in any scientific and/or regulatory context requiring expertise in the ATMP sector.
The Ministerial Decree 7 September 2017 "Therapeutic use of medicinal products undergoing clinical trials" regulates in Italy the access to experimental pharmacological therapies, including advanced therapy, to be used outside clinical trials, for patients suffering from serious or rare diseases or who are in danger of life when, in the doctor’s opinion, there are no further valid therapeutic alternatives. In order to access advanced therapy medicines through compassionate use, the requirement of availability of at least phase II study results remains valid.
Access to advanced therapy medicines not yet authorized or not subject to a specific clinical trial in Italy is possible, subject to AIFA’s authorization to production and use, in the absence of a valid therapeutic alternative, in cases of urgency and emergency when the patient is in danger of life or of a major damage to health.