The European Medicines Agency (EMA) has released a new reflection paper discussing how products are classified as advanced therapy medicinal products (ATMPs).
In the EU, medicinal products derived from genes, cells or tissues are classified as ATMPs. Because these areas of biomedicine are still in early stages of development and are fundamentally different from other types of medicine, the European Commission (EC) regulates them differently.
ATMPs are defined and regulated under Regulation (EC) No 1394/2007, which also establishes the Committee for Advanced Therapies (CAT), which is tasked with reviewing these products. In general, ATMPs fall into one of three categories, gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (sCTMP) and tissue engineered products (TEP).
Regulation (EC) No 1394/2007 also establishes incentives to promote the development of qualified ATMPs. These incentives include reduced fees for scientific advice and a procedure to help companies determine if their product can be classified as an ATMP.
Unlike traditional pharmaceuticals, the majority of ATMPs are developed by small- and medium-sized enterprises (SMEs). To account for this, SMEs receive a greater fee reduction for scientific advice and qualify for a 50% reduction in marketing authorization fees and post-authorization fees for one year after receiving marketing authorization.
While full legal definitions of ATMPs are found in Regulation (EC) No 1394/2007 and Commission Directive 2009/120/EC, EMA says "borderline cases [arise] where classification of a product based on genes, cells or tissues is not clear."
To address this issue, Regulation (EC) No 1394/2007 creates a classification procedure that allows "Any applicant developing a product based on genes, cells or tissues [to] request a scientific recommendation of the Agency with a view to determining whether the referred product falls, on scientific grounds, within the definition of an advanced therapy medicinal product."
After an applicant applies to this procedure, EMA has 60 days to return its recommendation to the applicant. To date, more than 100 products have been assessed by CAT under the classification procedure, with nearly 90% being classified as ATMPs.
While the procedure is optional and non-binding, EMA says it "can help developers clarify the applicable regulatory framework [and] should be seen as a first opportunity to engage with regulators."
Scientific Principles and Further Considerations
In addition to explaining the classification procedure and definitions of ATMPs, EMA's reflection paper also discusses several scientific principles involved in classifying these products.
Because Regulation (EC) No 1394/2007 excludes "products made exclusively of non-viable materials which act primarily by physical means," from being classified as ATMPs, companies should be able to demonstrate that the cells used in an ATMP are viable.
Companies should also carefully consider the claimed mode of action when applying for classification, as the mode of action can impact whether a product is classified as an sCTMP or TEP. In general, TEPs are used to regenerate, repair or replace tissue, while sCTMPs are used to treat, prevent or diagnose a condition based on "the pharmacological, immunological or metabolic action of its cells or tissues."
Additionally, the paper discusses several borderline issues, including the differences between advanced therapies and cell/tissue transplants. To be considered an ATMP, cell- and tissue-derived products must be subject to "substantial manipulation," or in some cases be used to perform a "different essential function" than the original cell/tissue would perform.
EMA Reflection Paper