The Ministry of Health approved the standard “Guideline. Medicinal products. Quality, preclinical and clinical aspects of medicinal products containing genetically modified cells,” developed by the State Expert Center.
Order of 16 February 2024 No. 264 has been published on the official website of the MoH: http://surl.li/qtctb
The guideline has been developed as methodological recommendations on the quality, preclinical, and clinical aspects of medicinal products containing genetically modified cells. The provisions reflect an approach based on the latest scientific achievements in this field of knowledge, harmonized within the EU and ICH (International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use).
The guideline is recommended for business entities engaged in:
- development, preclinical and clinical study
- submission of applications for state registration/re-registration of medicinal products in the territory of Ukraine regardless of departmental subordination and form of ownership
- for the relevant applicants and manufacturing enterprises whose products are registered and imported into Ukraine
- for scientific and expert organizations and experts who conduct expert evaluation during state registration (re-registration) of medicinal products
- for auditors and inspectors.
The document focuses on quality, preclinical aspects, and safety and efficacy requirements for genetically modified cells.
Yes, the quality section covers the requirements specific to the genetic modification of the target cell population and to the genetically modified cell product resulting from the manufacturing process. This section has been updated to reflect the evolution of science and regulatory experience, with an emphasis on starting materials (also taking into account the implications for genome editing reagents/tools), comparability, and validation.
The preclinical section concerns the preclinical studies required to assess the proof of concept and biodistribution of the medicinal product, to identify potential target organs of toxicity, and to obtain information on dose selection for clinical trials, to justify the routes of administration and the dosing regimen. This section has been supplemented with current views on the requirements for conducting preclinical studies and with a special section on scientific principles and recommendations for CART cell and TCR products, cell products based on induced pluripotent stem cells, and cell products obtained as a result of genome editing.
The clinical section addresses the requirements for studying the pharmacological properties of the cell itself and the transgene. The requirements for efficacy studies emphasize that the same principles apply as for the clinical development of any other medicinal product, especially those set out in the current guidelines relating to specific therapeutic areas. The clinical section also addresses the evaluation of the safety of the medicinal product, as well as the principles of follow-up and pharmacovigilance requirements. This section has been updated taking into account the experience of recent scientific advice and registration applications. An Annex on clinical aspects specific to CAR-T cells has been prepared and included.
Also included is the Annex on Good Clinical Practice (GCP) for advanced therapy medicinal products (ATMPs), which defines the specific GCP requirements for clinical trials involving ATMPs and supplements the Good Clinical Practice guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), which also apply to ATMPs.
