Biodistribution, shedding and persistence of gene/cell therapies was identified by ARDAT WP5 partners as a key area for the focus of regulatory and harmonisation activities in the ARDAT consortium. Despite the growing body of published research characterising biodistribution, persistence and shedding of ATMPs, a lack of common methodological standards and reagents to assess the presence and persistence of gene and cell-based therapies was identified as a key issue that could benefit from further regulatory harmonisation.
A multidisciplinary team from ARDAT have therefore collaborated on a regulatory landscape assessment in order to a) identify regional differences in regulation and b) identify opportunities for harmonisation and where new recommendations / standards may be proposed with regard to biodistribution, shedding and persistence.
A number of information sources were consulted as part of the landscape assessment and used to identify a preliminary list of issues that may benefit from regulatory harmonisation. The key sources were:
- Existing international guidelines (in particular EMA, FDA and ICH, with other relevant guidance from international sources consulted where appropriate).
- Feedback obtained from consortium partners from regulatory consultations (e.g., scientific advice) with EMA and other competent authorities.
- Public assessments of approved, withdrawn and rejected ATMPs.
After conducting the landscape assessment, a WP5 sub-team was set up to draft and publish a Whitepaper utilising the information collated from the landscape assessment and encompassing the following aspects:
- A comparative evaluation of global regulatory expectations for biodistribution, shedding (including environmental risk assessment) and bioanalytical methods.
- A description of methodological aspects for the construction of the database designed to collect published data on biodistribution and shedding.
- Use of the database to identify and discuss reporting inconsistencies across the published literature with regard to biodistribution and associated bioanalytical methods.
As the database has to date only collected data from AAV-based therapies, it was decided to focus on AAV-based therapies in the first Whitepaper. A preliminary analysis of the most relevant database outputs from the perspective of data-driven regulatory support in the context of AAV-based therapies was included in the Whitepaper. This analysis will inform similar approaches to other gene and cell-based therapies in the future and potential future articles / whitepapers from the consortium.
The finalised Whitepaper, entitled “Current global regulatory landscape for biodistribution & shedding assessment of rAAV gene therapies & recommendations of the IMI ARDAT consortium on future directions” was submitted for review at the journal “Cell & Gene Therapy Insights” on 18th March 2022 and was published on 26th April 2022.
Please follow this link to access the publication.