From the President’s Desk: The Rule of Regs

Recommend

Jacques Galipeau, MD FRCP(C)
President, ISCT
Don and Marilyn Anderson Professor in Oncology
Associate Dean for Therapeutics Development
University of Wisconsin School of Medicine and Public Health

Cell and Gene Therapies (CGTs), especially at the intersection of gene-modified cells, represent a novel class of living drugs distinct from transfusion medicine and organ transplantation. The key operative word is “drug” since it triggers oversight from regulatory agencies whose mission is protecting public health by ensuring the safety, efficacy, and security of drugs, biological products, and medical devices.

The safety and effectiveness of a drug is ascertained objectively through the collection of data from regulatory-approved clinical trials where endpoints span quality of life assessments (QOL) to survival. The judgements made for approval and subsequent commercial licensing are tempered by the equipoise assessment of safety adjusted for the severity and unmet needs of the ailment treated.

The distinguishing feature of CGTs from traditional medicinal chemistry and later developed biologics is the inherent complexity of living therapies where spectacularly complicated machines – living cells – are manufactured in a robust, reproducible method and are measurably potent akin to simple chemicals. Chess to Checkers really. That said, Regulatory agencies worldwide need to tackle the evolving demands of complex living drug platforms. We – academic and industrial CGT innovators – and our regulatory counterparts are building the plane as we are collectively flying it.

Since CGTs offer cures for the incurable in an incredible one-and-done paradigm, Regulators and the public are highly motivated to streamline the approval and deployment pathway for safe and effective game-changing CGT drugs. This rapidly evolving international regulatory landscape is brilliantly captured by the open-sourced publication of ISCT’ first biannual Global Regulatory Report on Cell and Gene Therapy. At the behest of our CCO – Tony Ting – this report was born from the labor of the ISCT volunteer GRTF committee: Bambi Grilley (USA), Dominic Wall (Australia), Christopher Bravery (UK), Karen Nichols (USA), Fernando Figueroa (Chile) and Gabrielle O’Sullivan (Australia) with ISCT Head Office support by Fajar Dumadi. It shows that year-over-year, cell therapies continue to make up the majority of all approved products (71%). However, the pipeline for genetically modified cell therapies has grown to include 1,150 therapies in development, compared to 839 non-genetically modified cell therapies and 920 gene therapies. The full report is a user-friendly 59-page PowerPoint formatted presentation that is a must-read!

The report also provides a complementary analysis of CGT deployment viewed through the regulatory lens with specific test cases approved in distinct international jurisdictions and highlights of the evolving regulatory landscape, including issues related to distributed and point-of-care manufacturing, amongst other themes. The report provides a first chapter on a new living document to be updated bi-annually and accessible through ISCT website that will provide further analytics inclusive of all jurisdictions active in CGT space.

To meet this goal and recognizing the growing impact of CGTs in regulatory jurisdictions far and wide and to advance internationally connected knowledge transfer, the ISCT sponsored as part of its Paris 2023 meeting the inaugural Global regulators summit co-chaired by our Chief Regulatory Officer – Bambi Grilley - and our Chair of the ISCT ECGT committee – Laertis Ikonomou. The remit of the day long panel was focused on mapping the Global Regulatory Landscape and its impact on oversight, enforcement and outcomes. Representatives of fourteen international agencies were present including: CAT-EMA (EU) ; AGES MEA (Austria), CBER-FDA (USA) ; ANVISA (Brazil) ; Institute for Standardization & Control Pharmaceuticals, Ministry of Health (Israel) ; TGA (Australia) ; Office of Cellular and Tissue-based Products, PMDA (Japan) ; ICMR (India) ; Ministry of Health and Welfare Korea (Korea); Hong Kong Department of Health (Hong Kong); Health Canada (Canada); European Directorate for the Quality of Medicines and Healthcare (EDQM) ; UK MHRA (United Kingdom) ; Health Innovation and Substances of Human Origin (DG SANTE), European Commission (Belgium)

. From this and future summits, the ISCT and its Global Regulatory Task Force will grow its biannual Global Regulatory Report on CGT to reflect a shared international reality.

ISCT is positioned as the society with a pragmatic global perspective inclusive of all international jurisdictions in a manner not otherwise achievable. Information gathered, and best practices shared will provide the CGT ecosystem with a roadmap to optimize the global deployment of safe and effective living therapies.

References

https://www.fda.gov/about-fda/what-we-do#mission
https://www.isctglobal.org/resources/regulatory--quality-initiatives/regulatory-report
https://www.isctglobal.org/about/isct-committees/grtf
https://www.fda.gov/about-fda/fda-organization/center-biologics-evaluation-and-research-cber
http://antigo.anvisa.gov.br/en/english
https://www.health.gov.il/English/MinistryUnits/HealthDivision/MedicalTechnologies/Drugs/ISCP/Pages/default.aspx
https://www.tga.gov.au/
https://www.pmda.go.jp/english/rs-sb-std/sb/subcommittees-1st/ctp/0010.html
https://main.icmr.nic.in/
http://english.nmpa.gov.cn/2019-07/19/c_389166.htm
https://www.canada.ca/en/health-canada.html
https://www.edqm.eu/en/
chttps://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency
https://commission.europa.eu/about-european-commission/departments-and-executive-agencies/health-and-food-safety_en