Describing the landscape of European Union guidance applicable to Advanced Therapy Medicinal Products (ATMPs) and discussing its specificity

Guidance documents are essential to developers and manufacturers of Advanced Therapy Medicinal Products (ATMPs). They are essential to embed quality, safety and efficacy aspects when designing clinical trials and applying for marketing approval, and ultimately, they contribute to guarantee rapid and safe access to ATMPs. Nevertheless, they are widely overseen because of their numbers, diversity and on some occasions redundancy, overlap or inconsistencies. This situation results from their genealogy being linked to scientific advances occurring in discrete steps and in distantly related areas of development or application. We here looked at the entire set of European guidance adopted in the field of ATMPs, and we questioned the specificity of ATMPs as a specifically regulated category of biological medicines. We collected 126 guidance documents applicable to ATMPs, that mainly come from the European Medicines Agency (EMA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). We demonstrated the specificity of ATMPs as for the majority of currently applicable ATMPs guidance documents there is no overlapping with other categories of biological medicines. We highlighted there is a drive from regulators, especially the EMA, to ensure that all documents applicable to ATMPs are accessible in one place, on the EMA website, despite important overlapping of guidance applicable to biological medicines. We argued that complexity and confusion may come from the large quantity and high diversity of guidance applicable to ATMPs, and that their navigability could be improved.

This paper covers European Union guidance documents that apply to Advanced Therapy Medicinal Products (ATMPs) developed at the industrial scale, and which are intended to be commercialised in the European Union. It is an interdisciplinary paper regarding both its methodology, its analysis. The co-authors are academia researchers, public hospital clinicians and/or doctors specialised in law, biotherapies, molecular biology, pharmaceutical sciences, cell therapy.

• 126 guidance documents applicable to ATMPs were collected from July 1990 to the 8 September 2023.
• The guidance documents applicable to ATMPs are mainly guidelines coming from the European Medicines Agency (EMA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).
• For the majority of currently applicable ATMPs guidance documents, there is no overlapping with other categories of biological medicines. It indicates they are strictly specific to ATMPs, and that the singularity of ATMPs is well reflected through their guidance landscape. 
• Despite important overlapping of guidance applicable to biological medicines, there is a drive from regulators, especially the EMA, to ensure that all documents applicable to ATMPs are accessible in one place, on the EMA website.
• Complexity and confusion may come from the large quantity and high diversity of guidance applicable to ATMPs:
  • Almost no difference is made between Cell Therapy and Tissue Engineering medicinal products in guidance documents while they are two distinct subcategories of ATMPs in the legislation. 
  • There is a near absence of link between ATMPs and Biosimilar medicines guidance documents. It suggests guidance documents on Biosimilar medicines were not thought for ATMPs due their recent development and low number in comparison with biotechnological medicines (such as medicines based on monoclonal antibodies).
• The current navigability of ATMPs guidance could be improved.

• Introduction
• Methodology
• Results
  • Guidance documents related to ATMPs
  • Distribution of currently applicable ATMPs guidance documents
  • Overlap of ATMP guidance documents with other legal categories of biological medicinal products
  • Detailed intersections within currently applicable ATMP guidance documents 
• Discussion
• Conclusion

Full reference of the paper: 

Aurélie Mahalatchimy, Valentin Roby, Julie Véran, Christian Chabannon, Florence Sabatier, Mapping the European landscape and specificity of ATMPs guidance, Cytotherapy, 2025, Epub 20 June 2025, Volume 27, Issue 10, p.1262-1269, October 2025, DOI: 10.1016/j.jcyt.2025.06.008

Open Access link to the paper:

https://www.isct-cytotherapy.org/article/S1465-3249(25)00747-9/fulltext