Progress in the development of advanced therapy medicinal products (ATMPs) is in part closely linked to the concept of individualised medicine. The evaluation of ATMPs is quite complex and therefore requires special knowledge that the Paul-Ehrlich-Institut has at its disposal.
ATMPs, a highly complex group of medicinal products applied directly to patients, is comprised of gene therapeutics, somatic cell therapeutics, and tissue engineered products.
After many years of development, the number of marketing authorisations issued for these medicinal products is now rising significantly. Five gene therapeutics were authorised in 2021 and 2022 alone. CAR-T cells, which are genetically modified autologous immune cells (T cells) outside the patient's body and which have hitherto been used in the therapy of certain blood cancers (leukaemias, lymphomas), are now also being developed for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE). The Paul-Ehrlich-Institut evaluates and approves clinical trials with these novel medicinal products for Germany and carries out the evaluation of European applications for authorisation in the CHMP at the European Medicines Agency. In addition, the Paul-Ehrlich-Institut provides national and international scientific advice on ATMPs and is responsible for ATMP vigilance.
Preventive mRNA COVID-19 vaccines experienced a high level of public perception and appreciation during the pandemic. However, mRNA-based gene therapeutics are also being developed, including tumour immunotherapeutics, such as those that work in combination with CAR-T cells. The Paul-Ehrlich-Institut is actively involved in the European authorisation process and often serves in a leadership position in these procedures.
The experts of the Paul-Ehrlich-Institut also deal intensively with scientific regulatory aspects. One example of their work in this area was the first publication in the EU on clinical trials using CRISPR-generated autologous somatic cells.
Initiatives such as the international public ATMP workshop held at the Paul-Ehrlich-Institut in 2022 are important contributions to support the development of innovative gene therapy drugs. The workshop fostered dialogue between developers and regulators and provided a good framework to discuss new developments such as gene editing and RNA-based gene therapeutics.
The workshop also provided insights into the scientific regulatory requirements in the area of clinical trials and the challenges with regard to the establishment of the new regulations of Regulation (EU) No 536/2014 on clinical trials. Another topic covered was the clinical testing of medicinal products containing genetically modified organisms (GMOs). For GMO clinical testing, the Paul-Ehrlich-Institut grants the necessary release permit after consultation with the Federal Office for Consumer Protection and Food Safety (Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, BVL), which is responsible for the release permit in accordance with the Genetic Engineering Act in Germany. The release permit is issued at the same time as the approval of the clinical trial.
Due to its wide-ranging areas of involvement, the Paul-Ehrlich-Institut is an important authority in Europe and internationally for the development and authorisation of ATMPs.
We are pleased that after many intensive years of development, advanced therapy medicinal products are now increasingly finding their way into authorisation. We are proud to be able to actively accompany this journey.
Dr Anneliese Hilger (Head of the Haematology, Cell and Gene Therapy Division)
Anliker B, Childs L, Rau J, Renner M, Schüle S, Schuessler-Lenz M, Sebe A (2022): Regulatory Considerations for Clinical Trial Applications with CRISPR-Based Medicinal Products.
CRISPR J 5: 364-376.