Cell & Gene

10 January 2023

An Overview of ATMP Regulation and Classification


Jay Lad
Director

What Exactly Are ATMPs and How Are They Classified & Regulated?

Advanced therapy medicinal products (ATMPs) including breakthrough cell and gene therapies, offer unprecedented promise for the long-term management and even cure of disease – especially in areas of high unmet medical need. These advanced therapies are driving an exciting and revolutionary new paradigm in science and healthcare.

But what exactly are ATMPs? In this article, we take a closer look at this exciting therapy.

What are ATMPs?

ATMPs are medicines intended for human use that offer revolutionary opportunities for the treatment of both disease and injury. They are classified as:

  • Gene therapy medicines: Medicines containing genes that lead to therapeutic, prophylactic, or diagnostic effect, they work by inserting “recombinant” genes (a stretch of DNA created in the laboratory) into the body to treat diseases.
  • Somatic-cell therapy medicines: Medicines used to cure, diagnose, or prevent diseases, somatic-cell therapy medicines contain cells manipulated to change their biological characteristics, which may not be used for the same essential functions as before.
  • Tissue engineered medicines: Medicines that contain modified cells or tissues used for the repair, regeneration, or replacement of human tissue.

As of August 2022, no more than 16 ATMPs are approved by the European Medicines Agency (EMA). So far, 11 ATMPs have valid marketing authorisation, with more expected to meet approval in the coming years. Like any medicine, ATMP regulation is strictly controlled. In Europe, the EMA’s biological products framework regulates ATMPs (Directive 2001/83/EC), and defines the legal basis for development. In the UK, however, ATMPs are regulated by The Medicines and Healthcare products Regulatory Agency (MHRA), which authorises ATMP clinical trials as well as ATMP manufacturing and importing.[1]

ATMP Classification Overview

The EMA sets four main classifications in Article 2 of Regulation (EC) No 1394/2007, which we will outline below alongside examples of use for each.

Subclassification of ATMPs
Gene therapy medicinal product (GTMP)

GTMPs contain or consist of a recombinant nucleic acid which must be of a biological nature and should be directly involved in the mechanism of action. GTMPs regulate, repair, replace, add to or delete genetic sequences. An example of a GTMP in action is found in a medicine known as Lexturna, used for the treatment of vision loss due to inherited retinal dystrophy linked to biallelic RPE65 mutation.

Somatic cell therapy medicinal product (sCTMP)

sCTMPs consist of cells or tissues subjected to either substantial manipulation or are not intended for their original function in the recipient and donor. This kind of ATMP is used to either treat, prevent or even diagnose disease through the action of its cells or tissues — this can be via pharmacological, immunological or metabolic action. sCTMPs are used in the medicine, Alofisel, which is used to treat complex anal fistulas in adults suffering from Chron’s disease.

Tissue-engineered product (TEP)

Like sCTMPs, TEPs consist of engineered cells or tissues subjected to substantial manipulation and are not intended for their original purpose in the recipient. The purpose of TEPs is to repair, replace, or regenerate human tissue. TEPs are used in the medicine, Spherox, which is used to repair defects within knee cartilage.

Combined ATMP

A combined ATMP must work as an integral part of or must incorporate one or more medical devices and a cellular or tissue component. The component must also contain viable (living) or non-viable (non-living) cells.  An example of a combined ATMP in use is cells embedded in a scaffold used in tissue engineering.

To further understand what classification your ATMP is likely to be classified as – if at all – you can use this decision tree as published by the EMA.

 

Advice for Applying for ATMP Classification

While ATMP classification is free and legally non-binding, there are a variety of factors that a developer must consider before applying. Although the procedure for ATMP classification is optional, a successful ATMP classification may help developers gain access to unique EMA services and incentives.

Documents Required

When applying for ATMP classification, two documents are required for submission. The first document is an administrative form that requests details including the product name, description of active substance, indication, company details and a date of submission. The form (submitted as a single-tab Excel sheet) must also match the information on the second required document —  the ATMP classification briefing document. The briefing information document should contain information about the product, its development (such as quality and manufacturing details), and the outline of clinical and non-clinical development work. The scientific aspects of the application are broken down into the following steps:

  1. Active substance: Description of active substance, additional substances, and medical device.
  2. Finished product: Details on qualitative and quantitative composition, mode of administration, pharmaceutical form, plus the description of the finished product when ready for clinical use.
  3. Mechanism of action: Claimed mechanism of action, the properties of that action and proposed uses, including therapeutic, prophylactic, or diagnostic.
  4. Summary of the status of the development of the product: Key elements of manufacturing aspects, including outlines of clinical and non-clinical development.

Procedure

Applications must be submitted on the EMA website before the allocated deadlines outlined on the Advanced therapy classification page. ATMP classification requests should be received by the EMA at least 15 days before the start of the procedure for inspection and the request for additional information if required.

Publication

The Committee for Advanced Therapies (CAT) then initiates a draft preparation period where it meets to discuss the draft scientific recommendation. As a result of the meeting, the committee then delivers the outcome after consultation with the European Commission. In all, the procedure should be finalised no longer than 60 days after the receipt of the original request.

What Does the Future of ATMPs Look Like?

It is clear that ATMPs have high potential to be beneficial to patients’ health and wellbeing in the future, but there is still significant work to be done to understand their full health impact.

Due to the wide range of applications that ATMPs could eventually be used for, there is already a lot of work going on to research and develop ATMPs fully, with positive results from clinical trials already resulting in significant investment and resources being allocated to this field.

Developing new ATMP products is just the start however. Taking the time to understand the classification and regulation of these products is just as important for businesses looking to get involved in this exciting field.

List of References


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