The recent development in cellular and molecular biotechnology, has resulted in the growth of a new segment of biological medicinal products and paved the way for Combined Advanced Therapy Medicinal Products (CATMPs). These products are regulated in the EU under the Advanced Therapy Medicinal Product (ATMP) Regulation and are defined as containing one or more medical devices as an integral part of the product. They offer ground-breaking new treatment and prevention opportunities for many diseases, dysfunctions and injuries to the various parts of the human body.
Nevertheless, the development of these products also presents challenges in the form of precise requirements, regulations and associated guidelines. Here are 6 regulatory related questions you should ask when developing CATMPs.
1. What are the different types of CATMPs?
CATMPs are of three types:
1. Gene therapy medicinal products - containing genes that elicit a therapeutic effect and work by inserting "recombinant" genes into cells
What do they treat?
A variety of genetic disorders, e.g. cancer or chronic diseases
2. Somatic cell therapy medicinal products - containing cells or tissues that have been manipulated to change their biological characteristics
What do they treat?
Cure, diagnose or prevent disease, e.g. the use of patient's
manipulated cancer cells to fight the remaining cancer cells in their body
3. Tissue engineered products - containing cells or tissues that have been modified
What do they treat?
Repair, regenerate or replace tissue, e.g., artificial skin used to treat patients with burns
Note: There is not a class of product called a "combination product", and most products combining a medicine with a medical device are regulated under either the medicinal product legislation or the medical device legislation, depending on the product's principal intended action.
2. What does the regulatory framework include?
The regulatory framework for CATMPs was realized in December 2008. The framework contains information on the application of CATMPs:
- Authorization procedure
- Supervision and monitoring to ensure safety and effectiveness
- Incentives to encourage research and development (R&D) in the area of these therapies
- Provides fee reductions for scientific advice (SA)
- Marketing authorization applications (MAAs) centrally via the European Medicines Agency (EMA) (The EMA continues to monitor the safety and effectiveness of ATMPs, once marketed).
3. What does the application process for CATMPs look like?
The Committee for Advanced Therapies (CAT) plays a central role in scientific assessment, and provides the necessary expertise to evaluate ATMPs. During the assessment procedure, the CAT prepares a draft opinion on the quality, safety and efficacy of an ATMP, which is sent to the Committee for Medicinal Products for Human Use (CHMP). Based on the CAT opinion, the CHMP adopts a recommendation and on that basis the European Commission may grant or refuse an MA.
The CAT also provides recommendations on:
- The classification of ATMPs
- Reviews data of products developed
- Contributes towards SA on ATMPs
- Encourages the development of ATMPs
- Provides scientific expertise for any initiatives related to the development of innovative products and therapies at the request of the Commission
For medicinal products with an integral delivery device element, the details of the device aspects are included in the Quality Module of the submission documentation. Learn more about integral delivery device elements.
4. How do I determine if my product is a CATMP?
Article 17 of the ATMP Regulation highlights that companies can apply to the EMA to determine whether a product they are developing is an ATMP. The EMA established this procedure to address questions of borderline classification with other areas such as medical devices. The CAT will deliver scientific recommendations on ATMP classification after consultation with the Commission within 60 days after receipt of the request.
Typically, numerous national agencies/authorities regulate various aspects of ATMPs, and it is different in every EU member state (MS), but some MSs provide a single point of contact to ease the regulatory burden, e.g., in the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) Innovation Office.
A product is classified as a CATMP when it fulfils the definitions provided in Article 2(1)(d) of the ATMP Regulation, i.e., incorporates an active substance and one or more medical devices as an integral part of the product.
5. What are the challenges of developing CATMPs?
An increasing number of innovative biological products have characteristics that may fall under different regulatory requirements (e.g., medicines, medical devices, cosmetics, or tissues and cells), and cases have arisen where the CAs of different MSs came to different conclusions on whether a product could be considered an ATMP. This could imply that the level of public health protection differs across the EU, and these differences undermine the incentives to develop ATMPs, due to uncertain market potential, distorted competition, and hindrance of free movement.
In fact, the larger Pharma companies constitute for less than 2% of all ATMP clinical trial sponsors, only 5% of all ATMP classification requests and less than 10% of SA requests in respect of ATMPs. Again, indicating that these companies are not engaging in ATMP development to date, as a result of the high associated risk.
However, The EMA ATMP classification procedure was designed to reduce these problems and there are now a number of successful ATMP products.
6. What lies ahead for CATMPs?
The EU Commission have also identified a number of actions that could be taken to improve the application of the ATMP Regulation:
- Fine-tuning of ATMPs definitions and regulatory framework to address innovative new products
- Measures to reduce classification disparities across the EU
- Streamlining MA procedures
- Consideration of reduced fees for post-marketing obligations
As knowledge of CATMPs rapidly grows, there are many products with encouraging clinical trial results and the overall development of CATMPs continues to show steep growth and remains one of the most exciting and challenging pharmaceutical sectors. However, evaluating these novel products often requires specific expertise in their classification, development, manufacture and regulation compared with conventional products and there is a need to balance between the requirement to ensure CATMPs are made available to patients only after their quality, safety, and efficacy have been demonstrated.
Learn more about the EU regulatory requirements, pathways and processes of CATMPs in our journal article.