New European Pharmacopoeia Commission approach to gene therapy

Genetic Engineering. The study of the structure of DNA and RNA, the introduction of changes at the gene level. Modern medical research of stem cells. 3D illustrations

General chapter 5.14. Gene transfer medicinal products for human use was first published in European Pharmacopoeia (Ph. Eur.) Supplement 5.6 in 2006, when there were no approved gene therapy medicinal products (GTMPs) on the European market. Several GTMPs have since been approved and an ever-growing portfolio of ongoing clinical trials is likely to result in even more being launched on the European market, holding promise for the treatment of a wide range of different conditions. With gene therapy becoming a reality, the need for a standardised way of controlling these products prompted the European Pharmacopoeia Commission (EPC) to define a new approach to GTMPs for human use in March 2020 and include this area as one of its priorities for 2023-2025.

At its 178th session held on 19-20 March 2024, the EPC adopted the general monograph Gene therapy medicinal products for human use (1386) and the accompanying general chapter Additional information on gene therapy medicinal products for human use (5.34), which will replace general chapter 5.14.

In addition to a general requirements section containing provisions on the production of all GTMPs and specific requirements for recombinant vectors and genetically modified cells for human use, general monograph 3186 contains three individual sections describing additional requirements for the classes of GTMPs currently approved in Europe:

  • genetically modified human autologous cells modified by integrating retroviral or lentiviral vectors;
  • adeno-associated virus vectors for human use;
  • oncolytic herpes simplex virus for human use.

The accompanying general chapter 5.34 includes recommendations on product classes that are not yet on the European market to assist users and contains:

  • the revised remaining sections of chapter 5.14, covering:
    • plasmid vectors for human use;
    • adenovirus vectors for human use;
    • poxvirus vectors for human use;
    • retroviridae-derived vectors for human use.
  • a newly drafted section on genetically modified bacterial cells for human use.

In addition, general chapter 5.2.12. Raw material of biological origin for the production of cell-based and gene therapy medicinal products has also been revised to align it with this new approach.

The new general monograph provides a common framework of requirements for GTMPs, while offering the level of built-in flexibility judged necessary for these products, given the rapidly evolving nature of the field. This new approach marks an important milestone on the path towards a standardised way of controlling GTMPs and, together with the extensive additional guidance provided to users in the new general chapter 5.34, contributes significantly to enhancing public health in Europe and beyond.