Advanced therapy refers to new medical products that use gene therapy, cell therapy, and tissue engineering. They can be used to treat diseases or injuries, such as skin in burns victims, Alzheimer's, and cancer or muscular dystrophy, and have huge potential for the future of medicine.
EU Framework for Advanced Therapies
The EU's Regulation on advanced therapies, is designed to ensure the free movement of advanced therapy products within Europe, to facilitate access to the EU market, and to foster the competitiveness of European companies in the field, while guaranteeing the highest level of health protection for patients.
What are the main elements of the Regulation?
- A centralised marketing authorisation procedure.
- A multidisciplinary expert Committee (Committee for Advanced Therapies), within the European Medicines Agency (EMA), to assess advanced therapy products.
- Technical requirements adapted to the particular characteristics of these products.
- Special incentives for small and medium-sized enterprises.
The Regulation recognises that some advanced therapy products combine biological materials, such as tissues or cells, with chemical elements such as metal implants or polymer scaffolds. These combination products require adapted regulatory requirements.
GMP for ATMPs
The European Commission adopted Guidelines on Good Manufacturing Practice (GMP) specific for Advanced Therapy Medicinal Products (ATMP) in November 2017. The Guidelines provide a specific GMP framework that is adapted to the specific characteristics of ATMP.
GCP for ATMPs
The European Commission adopted Guidelines on Good Clinical Practice (GCP) specific for Advanced Therapy Medicinal Products (ATMP) in October 2019.
GMO requirements for investigational products
In-vivo gene therapy
A Good Practice document on the assessment of GMO-related aspects in the context of clinical trials with AAV clinical vectors has been developed. This document, which builds on possibilities under the existing legislation to facilitate the conduct of clinical trials with this type of medicinal products, has been endorsed by Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, the Netherlands, Portugal, Romania, Slovenia, Spain and Norway.
Developers that intend to conduct a clinical trial in these countries can follow the approach laid down in this document.
Moreover, a common application form has been endorsed by the competent authorities in Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, the Netherlands, Portugal, Romania, Slovenia, Spain and Norway.
A common application form for viral vectors has been endorsed by the competent authorities in Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, the Netherlands, Romania, Slovenia, Spain and Norway.
Specific application forms developed for certain categories of medicinal products prevail other this application. For example, developers of AAVs should use the common application form for investigational medicinal products for human use that contain or consist of AAV vectors.
Human cells genetically modified
A Good Practice document on the assessment of GMO-related aspects in the context of clinical trials with human cells genetically modified by means of viral vectors has been developed.
This document, which builds on possibilities under the existing legislation to facilitate the conduct of clinical trials with this type of medicinal products, has been endorsed by Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, the Netherlands, Portugal, Romania, Spain, Sweden and Norway.
Developers that intend to conduct a clinical trial in these countries can follow the approach laid down in this document.
Moreover, a common application form has been endorsed by the competent authorities in Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, the Netherlands, Portugal, Romania, Spain, Sweden and Norway.
Oncolytic viruses
A document on considerations for the evaluation of shedding from oncolytic viruses has been endorsed by the competent authorities in Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, the Netherlands, Portugal, Romania, Slovenia, Spain Sweden and Norway.
Repository of national regulatory requirements
Clinical trials with medicinal products that contain or consist of GMOs (Genetically modified organisms) are subject to both clinical trials and GMO legislations.
Dissemination of information about national regulatory requirements in respect of GMO aspects is expected to facilitate the development of gene therapy medicinal products in the EU.
- A repository of national regulatory requirements has been created to this effect
Action Plan on ATMPs
The Commission services and the European Medical Agency (EMA) have launched a joint action plan to foster the development of advanced therapy medicinal products (ATMPs), with the aim of streamlining procedures and better addressing the specific requirements of ATMP manufacturers.
The concept of similarity in an ATMP setting
This Q&A document addresses questions that have been raised by developers of ATMPs regarding the application of the concept of “similar active substance” in an ATMP setting. The Q&A document will be updated in light of accumulated experience during the assessment of these medicinal products.
