The EDQM (European Directorate for the Quality of Medicines & Healthcare) has released the 5th version of the Guide to the quality and safety of tissues and cells for human application on 15 December 2022.
This updated version results from an extensive revision and represents a major step forward for the human microbiome field. Indeed, the two chapters on human milk and intestinal microbiota have been moved up to part B, on “Specific requirements for substances of human origin” (Chapters 31 and 32, respectively), and the content of these chapters has been greatly improved. These 2 chapters, first introduced in the 4th Edition of the Tissue and Cells Guide in 2019, were initially included in the section of the guide on “developing applications”.
Regarding these changes on human milk and intestinal microbiota in the 5th Edition, EDQM states on their website:
“While the regulatory status of these substances may vary from country to country, the risks associated with their human origin and the processes applied to donor selection, procurement, processing and preservation serve the same purposes and are analogous to those of the rest of the tissues and cells described in this guide. Without intending to pre-empt any regulatory decisions, these chapters therefore provide a generic quality and safety framework for tissue establishments or any facility dealing with these substances.”
(https://www.edqm.eu/en/guide-to-the-quality-and-safety-of-tissues-and-cells-for-human-application)
It is important to note that Chapter 32 on “intestinal microbiota” has doubled in length, and now discusses in more detail critical topics, such as:
-
legal status
-
donor recruitment and pre-screening
-
donor testing
-
procurement and processing
-
quality management
Also, 2 new paragraphs address the topics of traceability and biovigilance.
The donor recruitment section now addresses the two principal aims of the selection of feces for FMT:
-
prevent adverse events associated with the transfer of pathogenic bacteria or viruses from fecal material
-
avoid transmission of impaired microbiota that could be ineffective or even harmful to the recipient
This second point is entirely novel as compared to the previous version of this chapter and raises important questions about the definition and threshold used to define an “impaired microbiota”. This section, as well as the section on quality control, also raises the issue about the lack of validated analytical tools and tests. These questions represent major regulatory science topics that could benefit from pre-competitive research programs to fill these important gaps and move the field towards more relevant quality standards for intestinal microbiomes, especially if indications other than recurrent Clostridioides difficile infection are envisaged soon.
The release in December 2022 of the 5th version of the EDQM guide is of the utmost importance for all microbiome stakeholders; indeed, the proposal for a regulation on standards of quality and safety for substances of human origin (SoHO) intended for human application now includes human microbiomes as SoHO (first draft made public in July 2022).
Furthermore, this text also proposes that expert bodies such as EDQM and ECDC (https://www.ecdc.europa.eu/) would be the nominal experts for the development of guidelines on quality and safety. As such the PRI therefore encourages anyone involved in the microbiome field to make themselves familiar with the present version of the guide and to monitor its ongoing development alongside that of the new SoHO Regulation.
It is however regrettable that Chapter 32 only mentions intestinal microbiota, and considerations on quality standards for the collection of other human microbiomes did not find their way into the ‘developing applications’ part of the guide.
About the European Directorate for the Quality of Medicines (EDQM) | https://www.edqm.eu/en/
The EDQM is a leading organisation that protects public health by:
- enabling the development,
- supporting the implementation and
- monitoring the application
of quality standards for safe medicines and their safe use which are recognised as a scientific benchmark and applied worldwide.
The guidance and standards developed by the EDQM in the areas of blood transfusion, organ, cell and tissue transplantation and consumer health issues have a positive impact on public health in Europe and beyond.
