ATMP stands for Advanced Therapy Medicinal Product. ATMPs differ from existing medicinal products in their nature, qualities, and manufacture. They are a heterogeneous medicinal product class that includes the following four medicinal product groups:
ATMPs open up a variety of new avenues for the treatment of diseases or dysfunctions of the human body, as these medicinal products usually address the causes of a disease and thus often offer options for a cure. The complexity of ATMPs requires special expertise in assessing their quality as well as their safety and efficacy. The Paul-Ehrlich-Institut has many years of experience and the necessary scientific background, not least due to its own research activities.
The Paul-Ehrlich-Institut, as the Federal Institute for Vaccines and Biomedicines, is responsible for the evaluation of the ATMP medicinal product class in Germany.
Updated: 03.04.2025
Gene therapy often involves the introduction of recombinant nucleic acids – deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) – into the patient's somatic cells with the help of a gene shuttle. These gene shuttles can be virus-based (e.g. non-replicating viral vectors) or synthetic, non-viral vectors (e.g. lipid nanoparticles). The vectors can either be injected directly into the human body so that gene transfer into the cells takes place in the body (in vivo gene therapy) or cells are taken from the patient or the healthy donor that are then modified by gene transfer and then returned to the patient (ex vivo gene therapy).
An example of in vivo gene therapy is the treatment of haemophilia A or B, in which patients suffer from bleeding due to a genetic deficiency of a coagulation factor (factor VIII, factor IX). In this type of gene therapy, the intact gene with the blueprint for the formation of the coagulation factor, e.g. with non-replicating viral vectors, is transferred to a few of the patient's somatic cells, in this case liver cells. The genetically modified liver cells form the functional coagulation factor in the body, which in turn can prevent bleeding.
An example of ex vivo gene therapy is the treatment of severe immunodeficiencies in which certain proteins cannot be formed due to genetic factors. Blood stem cells taken from the patient are genetically modified ex vivo by adding the intact gene for the formation of the functional protein. The cells, which have been functionally corrected with the addition of the gene, are infused into the patient and can then remedy the immunodeficiency. This approach is used for patients such as children who suffer from the rare and severe hereditary disease ADA-SCID (adenosine deaminase-deficient severe combined immunodeficiency).
Another example of ex vivo gene therapy is a treatment known as CAR T-cell therapy. This therapy involves the removal of certain immune cells from patients with haematological tumours. Those cells are genetically modified in such a way that they attack and destroy the patient's tumour cells after re-infusion.
In addition to the "gene addition" described in these examples, in which a gene is introduced into the patient's cell and acts as a blueprint for the formation of a protein to treat the disease, genome editing is another approach to gene therapy. During genome editing, the gene therapy product causes a specific mutation in the genome of the patient's cells in order to treat their disease.
Updated: 03.04.2025
Somatic cell therapeutics consist of cells or tissues that have been processed so that their biological features, functions, or structural properties are altered or that are used to perform a function from their original function in the recipient (non-homologous use). Many of the cell-based ATMPs function via genetic modification and can therefore often also be classified as gene therapeutics.
There are many somatic cell therapeutics in development. For example, studies are being conducted to determine whether diabetes can be cured by transplanting insulin-producing islet cells. Since human islet cells are only available to a very limited extent, animal (e.g. from pigs) are also being used in tests for this purpose. Such therapies that involve the use of animal cells are called xenogeneic cell therapeutics.
Further efforts include research into administering cells to regenerate heart muscles damaged by an infarction.
Updated: 03.04.2025
Tissue engineered products (TEPs) involve the substantial processing of cells or tissue to use them for the regeneration or replacement of human tissue. For example, cartilage cells are taken from the body and then cultivated/multiplied, after which they are re-implanted in the patient's knee to regenerate cartilage damage. Another example is stem cells taken from the eye via a small biopsy that are then multiplied and used to regenerate the cornea after a burn.
Updated: 03.04.2025
Advanced Therapy Medicinal Products (ATMPs) marketed in Europe require an official marketing authorisation. The authorisation is granted by the European Commission (EC) for the entire European Economic Area (EEA), once the Member States of the EU have issued an opinion stating that they consider the benefit-risk ratio of the ATMP to be favourable after having reviewed the data and information submitted by the applicant. Two Member States independently assess the quality, safety and efficacy of the ATMP as rapporteurs or co-rapporteurs. They then discuss and finalise this assessment with the other Member States in the relevant European bodies – the Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP). The Paul-Ehrlich-Institut has extensive and long-standing expertise in the area of ATMPs, so it often assumes the role of rapporteur or co-rapporteur. The European Medicines Agency (EMA) coordinates this process, known as the centralised assessment procedure.
Updated: 03.04.2025
Under special conditions, advanced therapy medicinal products (ATMPs) do not require a centralised marketing authorisation but can instead be used on the basis of the hospital exemption in accordance with section 4b of the Medicinal Products Act (Arzneimittelgesetz, AMG). Section 4b of the AMG is a special regulation specifically for ATMPs that are not routinely prepared and prescribed in Germany for an individual patient but are prescribed individually and are used in a specialised healthcare facility (e.g. hospital or doctor's office) under the professional supervision of a doctor in Germany. The preparation is also not considered routine if the ATMP is still in development and the findings necessary for a comprehensive assessment in the context of an application for marketing authorisation are not yet available. The ATMP must also be produced in accordance with specific quality standards – Good Manufacturing Practice (GMP).
Such ATMPs can then be marketed with a section 4b approval. A prerequisite for the granting of a section 4b approval by the Paul-Ehrlich-Institut is sufficient information on the quality, mode of action, effect and risks and a resulting favourable benefit-risk assessment. This special regulation allows patients early access to novel ATMPs and thus creates additional therapy options. However, the collection of further data for these therapies in clinical trials remains important in order to create a more comprehensive evidence base for the evaluation and ideally also to enable a centralised marketing authorisation process.
Updated: 03.04.2025
CAR T cells are used for gene therapy. The production of CAR T cells involves the removal of white blood cells (lymphocytes) from a patient with certain forms of blood cancer. T cells are then obtained from that group of cells. The T-cells are equipped with the gene of a chimeric antigen receptor (CAR) outside the body with the help of a vector, multiplied, and then administered intravenously to the same patient. Crucial here is the CAR receptor, which is composed of various components (and is therefore chimeric) in such a way that the CAR gene-modified T cells can attack and destroy the patient's tumour cells.
In addition to the autologous CAR T cell therapy described above, allogeneic CAR T cell therapy is another promising approach that is in development. In allogeneic CAR T cell therapy, white blood cells are taken from healthy donors, gene-edited to prevent issues such as rejection reactions in the recipient, and equipped with a CAR gene. After some additional necessary manufacturing steps, the patient's CAR T cells are administered intravenously.
Several autologous CAR T cell medicinal products have already been authorised in the EU and are also used in the treatment of certain types of blood cancers. The Paul-Ehrlich-Institut has participated intensively, often in a leading role, in the expert assessment and the final benefit-risk assessment of these ATMPs.
Source: Paul-Ehrlich-Institut
Updated: 03.04.2025
