Products with Genetically modified Cells - Draft Guideline

Recommendation

7/8 May 2024

Annex 2 & Co. - GMP Compliance for Biopharmaceuticals - Live Online Training
Regulatory Requirements and Practical Implementation

In September last year you could read about the planned revision of the 2012 adopted EMA guideline for Medicinal Products containing genetically modified Cells relating to the fact that the scientific development of methods for genetic modification requires an adaptation to reflect the current state of the art. The guideline from 2012 focused on traditional methods for genetic modification based on the use of vectors carrying recombinant nucleic acids. But especially the field of genome editing technologies which allow a simple approach to genetic modification of cells has undergone an increasing scientific progress. Such new technologies, maybe working with different starting materials or manufacturing processes, should be included in such a guideline, too.

In July, the EMA published a draft version of the revised guidance "Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells". In the following sections, the document covers the scientific principles for medicinal products containing genetically modified cells:

• Legal basis
• Quality Aspects (from materials up to stability studies)
• Non-Clinical Aspects (from Pharmacodynamics up to toxicology)
• Clinical Aspects (from dose selection up to clinical follow-up)
• Pharmacovigilance
• Environmental Risk Assessment

Additionally, the special clinical considerations on CAR-T-cells will be covered in an Annex.

According to the EMA, the aim of the revised document is to provide guidance for products intended for human use and presented for marketing authorisation:

"The scope of this document is on medicinal products that contain genetically modified cells. Its focus is on quality, non-clinical and clinical aspects of genetically modified cells. All cases of genetically modified cells intended for use in humans are included, no matter whether the genetic modification has been carried out for therapeutic or other (e.g. for enhanced manufacturing) purposes.
Genetic modifications can be obtained through a variety of methods (e.g. viral & non-viral vectors, mRNA, genome editing tools). The genetically modified cells can be of human origin (autologous or allogeneic) or animal origin (xenogeneic cells), either primary or established cell lines. Genetically modified cells of bacterial origin are excluded from the scope of this guideline. In a medicinal product, the genetically modified cells can be presented alone or combined with medical devices. The requirements described in this document are those relating to market authorisation application but principles may apply to development stages."

The document is open for consultation until 31 July 2019. Comments may be submitted to CATsecretariat@ema.europa.eu.