Advanced Therapy Medicinal Products (ATMPs) are medicinal products for human use based on genes, tissues, or cells. They have a colossal treatment potential in diseases such as cancer, neurodegenerative, and cardiovascular diseases. ATMPs are typically used to treat severe diseases and injuries where the standard of care is not available or sufficient.
Advanced Therapy Medicinal Products can be divided into three categories: gene therapy, somatic-cell therapy, and tissue-engineered medicines.
Gene therapy medicines
Therapeutic, prophylactic, or diagnostic medicines that contain genes. Usually used to treat cancer, long-term diseases, or genetic disorders, gene therapy medicines work by inserting recombinant genes into the body. A recombinant gene is a DNA string created in a laboratory that combines DNA from different sources, thus creating DNA sequences that cannot otherwise be found in the genome.
Gene therapy medicinal products have the following characteristics according to the current regulations:
- It contains an active substance that contains or consists of a recombinant nuclei’s acid used in or administered to human beings with a view to regulating, repairing, replacing, adding, or deleting a generic sequence.
- Its therapeutic, prophylactic, or diagnostic effect relates directly to the recombinant nucleic acid sequence it contains or to the product of the genetic expression of this sequence.
Gene therapy medicines do not include vaccines against infectious diseases.
A good example of gene therapy medicines is oncolytic viral therapies for melanoma.
Somatic-cell therapy medicines
Medicines that contain cells or tissues that have been manipulated to allow them to be used for different purposes in the body than what they were initially intended for.
Somatic-cell therapy medicinal products:
- Contains or consists of cells or tissues that have been subject to substantial manipulation so that biological characteristics, physiological functions, or structural properties relevant for the intended clinical use have been altered, or of cells or tissues that are not intended to be used for the same essential function(s) in the recipient and the donor.
- Is presented as having properties for, or is used in, or administered to human beings with a view to treating, preventing, or diagnosing disease through the pharmacological, immunological, or metabolic action of its cells or tissues.
Somatic-cell therapy medicinal products are not considered substantially manipulated if they have been cut, ground, shaped, centrifuged, soaked, sterilized, irradiated, separated, concentrated or purified, filtered, lyophilized, frozen, cryopreserved, or vitrified.
An example of somatic-cell therapy medicinal products could be mesenchymal stromatolite cells (MSCs) used for arthritis and fracture repairs.
Tissue-engineered medicines
Cells or tissues that have been modified to repair, regenerate, or replace human tissues. Tissue engineering often consists of implanting cells, tissues, or organs in the body to repair or replace organs with impaired function.
Tissue-engineered products:
- Contains or consists of engineered cells or tissues. Engineered cells and tissues are defined as any cells or tissues subjected to substantial manipulation that serve a different function in the recipient than in the donor.
- Are presented as having properties for, or is used in, or administered to human beings with a view to regenerating, repairing, or replacing a human tissue.
Tissue-engineered medicinal products can consist of both human or animal tissues or both, and cells may be viable or non-viable. Additional substances, such as scaffolds, chemicals, or molecules, can be added.
A well-known example is lab-grown skin grafts for burn treatment.
Somatic-cell therapy medicines and tissue-engineered products are known as “regenerative medicine.”
Combined ATMPs
Additionally, as is the case with cells and tissues embedded in biodegradable matrices or scaffolds, advanced therapy medicinal products may be combined with medical devices.
When an ATMP is combined with a medical device, it must contain viable cells or tissues or be liable to act upon the human body with a primary action of the medical device to be considered a combination ATMP.
ATMPs vs. traditional transplants
Traditional transplants are not substantially manipulated before being transplanted and serve the same function in the recipient as in the donor. For example, bone marrow transplanted from the donor to the patient’s bone marrow is considered a traditional transplant, as it serves the same physiological function in both donor and patient. However, if the bone marrow were transplanted into the patient’s heart, it would be considered an advanced therapy medicinal product.
Regulatory requirements for ATMPs
ATMPs are not that different from other medicinal products regarding their regulatory requirements.
ATMPs require:
- Compliance with Good Manufacturing Practice (GMP) throughout the lifetime of the production process, including manufacturing and storage. GMP ensures product stability, reproducibility, and patient safety.
- Compliance with Good Distribution Practices (GDP) during transportation.
- Non-clinical animal testing in compliance with Good Laboratory Practice (GLP).
- Clinical trials following Good Clinical Practice (GCP) to ensure patient safety and clinical efficacy.
In the EU, Advanced Therapy Medicinal Products are regulated by the Medicinal Products Directive 2001/83/EC and Regulation (EC) No 726/2004. Combined ATMPs are additionally regulated by the Medical Devices Regulation (EU) 2017/745.
In the US, ATMPs are encompassed in Title 21 of the CFR, which deals with biological and medical devices.
