In 2007 the European Commission passed Regulation 1394/2007/EC regulating Advanced Therapy Medicinal Products (ATMPs). This act recognized the scientific progress in the various fields encompassed by the legislation and the need for more comprehensive legislation than existed previously. The types of products classed as ATMPs through this regulation include somatic cell therapies, gene transfer products, tissue engineered agents and combination products of medical devices with cellular or tissue material.
Before the EU Regulation became effective in 2008, products derived from genes and cells were mostly classified as pharmaceuticals, while tissue-engineered products were not explicitly covered by the existing legal framework. As a consequence, these products were only partly classified as pharmaceuticals or as medical devices. The lack of EU regulation in this field led to different approaches at the MS level. These varying approaches were counterproductive for the access to ATMPs and for the growth and competitiveness of the industry.
In USA, products classified as ATMPs by EU regulation are also subject to specific legislation and regulations but not under one umbrella as now exists in European Union (EU).
Details on Advanced Therapies European legislation
The new ATMP EU regulation was adopted in 2007 and became effective on 2008. Specifically, on 30 December 2008 legislation on advanced-therapy medicines came into force in the EU. The legislation defines what products are ‘advanced-therapy medicinal products’ and describes how they are authorized, supervised and monitored to ensure that they are safe and effective.
The ATMP legislation provides incentives to encourage research and development in the area of advanced therapies, by providing fee reductions for scientific advice and applications for marketing authorization. In the field of advanced therapies, the main actors are SMEs, academic spin-offs, not-for-profit organizations, and academia, since it is a research-intensive field, while the traditional pharmaceutical companies are not (yet) strongly involved because of the perception of high risk by this industry.
The new regulation was accompanied by a series of guidelines issued by EMA. It contains special rules with respect to the Directive on the creation of a Community code relating to medicinal products for human use (Directive 2001/83/EC) and the Regulation defining Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (Regulation (EC) No. 726/2004). In addition, advanced therapies can be used without a marketing authorization in domestic hospitals under the so-called hospital exemption. Taking into account this exemption, all the advanced-therapy medicines should be authorized centrally via the European Medicines Agency. They therefore benefit from a single evaluation and authorization procedure. As for all medicines, the Agency continues to monitor the safety and effectiveness of advanced therapies once they are on the market. The Agency also gives scientific support to companies to help them design systems used to monitor the safety of these medicines.
Incentives of the ATMP Regulation
The incentives applicable to ATMPs include exceptional circumstances, (partial) exemption from payment of fees, hospital exemption, optional certification procedure, scientific advice and a classification procedure:
- An exceptional circumstance could be provided when an applicant cannot show that he is able to provide comprehensive data on the efficacy and safety under normal conditions of use. Marketing authorization may be granted when the following conditions are met:
- the applicant completes an identified program of studies within a time period specified by the competent authority.
- the results shall form the basis of a reassessment of the benefit/risk profile.
- the medicinal product in question may be supplied on medical prescription only and may in certain cases be administered only under strict medical supervision.
- Hospital exemption can be gained; the medication should only be used under the exclusive professional responsibility of a medical practitioner. In addition, the product should be prepared and used within the same MS and an individual medical prescription for a custom-made product for an individual patient is needed.
- The (optional) certification procedure provides the developer with feedback about the quality and preclinical aspects in relation to the regulatory requirements. This procedure is meant as an incentive to SMEs in attracting capital and to facilitate the transfer of research activities to organizations that have the capacity to market medicinal products. In addition, SMEs will receive a 90% fee reduction.
- The classification procedure allows the developer to get a scientific recommendation from EMA, so developers know whether their product is classified as an ATMP. The advantages of this procedure is that the advice is EU-binding and free of charge.
- Partial exemption from payment of fees, for instance a 50% reduction for the marketing authorization fee.
- The ATMP developer can obtain scientific advice from the European Medicines Agency (EMA) as early as the development phase so that the authorization procedure has the greatest possible chance of success.