Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective

Abstract

With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications. For a new application, data and information relating to manufacturing processes and quality control of the active substance and the final product have to be submitted for evaluation together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMPs are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines. Due to the diversity of ATMPs, a tailored approach for regulating these products is considered necessary. Thus, a risk-based approach has been introduced for ATMPs allowing flexibility for the regulatory requirements. Since the regulatory framework for ATMPs was established, five products have been licenced in the European Union. However, the pipeline of new ATMPs is much bigger, as seen from the significant numbers of different products discussed by the CAT in scientific advice and classification procedures. In 2013, a public consultation on the ATMP Regulation was conducted by the European Commission, and the results were published in 2014. The report proposes several improvements for the current framework and established procedures for the regulation of ATMPs.

Advanced cellular therapy products based on mesenchymal stem cells

“…Ponadto wymagane jest, aby proces produkcji MSC jako sCTMP przebiegał w warunkach całkowicie sterylnych, a więc pomieszczenia i urządzenia muszą posiadać odpowiednie certyfikaty, procesy produkcji muszą zostać zweryfikowane przez właściwe organy, a personel powinien zostać odpowiednio przeszkolony. Finalnie otrzymany lek na bazie MSC musi spełniać wszystkie standardy GMP (czystość, skuteczność, dawka, stabilność genetyczna, żywotność komórek) [27].…”

Global Regulatory Differences for Gene‐ and Cell‐Based Therapies: Consequences and Implications for Patient Access and Therapeutic Innovation

“…Figure shows that the EU was the first jurisdiction to implement specific legislation for GCTs in 2007, the “Advanced Therapy Medicinal Product” (ATMP) Regulation 1394/2007. It amended Directive 2001/83/EC, which now includes a section with quality, safety, and efficacy requirements for approval of ATMPs . In parallel, a scientific committee that evaluates ATMPs was established (Committee for Advanced Therapies).…”

“…In parallel, a scientific committee that evaluates ATMPs was established (Committee for Advanced Therapies). Regulation 1394/2007 also includes incentives to develop ATMPs; fee reductions for scientific advice; an ATMP classification system; and a certification procedure for quality and nonclinical data . More recently, the Japanese Act for Pharmaceuticals, Medical Devices and Other Therapeutic Products was enacted in 2014.…”

“…For example, it offers a legal basis to deviate from technical requirements for quality . It can also be used to identify under which conditions a consistent ATMP can be manufactured . However, this approach does not allow deviations from EU GMP regulation…”

“…In these jurisdictions, developers can request scientific advice at any given point in time. In the EU, GCT developers benefit from a reduced fee for scientific advice . Furthermore, PRIME (EU), Sakigake (Japan), and Breakthrough Therapy Designation (US) all enhance opportunities for interaction between regulators and developers.…”