Authored By: Mo Heidaran, Vice President Technical, PAREXEL Consulting
The final guidance by FDA entitled “Expedited Programs for Regenerative Medicine Therapies for Serious Conditions” https://www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/cellularandgenetherapy/ucm585414.pdf
published in February 2019, refers to Regenerative Advance Therapy as a regenerative medicine therapy that meets certain criteria defined in section 506(g) of the FD&C Act which include cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products except for those regulated under section 361 of Public Health Service Act (PHS Act)(42 U.S.C. 264) and 21 CFR 1271(https://www.congress.gov/114/bills/hr34/BILLS-114hr34enr.pdf).
Although in the original definition of regenerative medicine therapy, as defined in paragraph 8 of the 21st Century Cures Act1, there was no mention of gene therapies. FDA, as a scientific matter, decided to include human gene therapies and genetically modified cells under this definition so long as these therapies lead to a sustained effect on cells or tissues. In addition, xenogenic cellular products are further defined to be regenerative medicine therapy based on further consideration.
It is important to note that regenerative medicine therapy, as defined in 21st Century Cures Act may not be consistent with previous definition and terminology of Regenerative Medicine after all.
Regenerative medicine is a term introduced in 1990’s by several early adopters of this field. Regenerative medicine does not necessarily have a well-defined, solidified definition but in general they are therapies that aim to treat patients with diseases or injury restore the function of disease or damaged tissue or organ by harnessing, stimulate or replace body’s own reparative properties (https://ac.els-cdn.com/S2213879X1500053X/1-s2.0-S2213879X1500053X-main.pdf?_tid=5fb18a7d-2d64-4553-9a3c-d024fee02a88&acdnat=1550757762_da5beecde14de0ae6afcb7509e5de11d)( https://www.liebertpub.com/doi/10.1089/152489001750056197).
Some treatments are disease modifying and/or curative and this can be by a variety of approaches, from cell-based, gene therapies, tissue engineering or other approaches. It is noteworthy that NIH defines Regenerative Medicine as a process of creating living functional tissue to repair or replace tissue or organ ( https://report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=62) which is entirely inconsistent with the definition set forth in the 21st Century Cures Act.
So what is the difference between the current definition of regenerative medicine and how it is defined in the 21 Century Cure Act and FDA guidance documents:
- Regenerative Medicine is a field in medicine that encompasses a novel approach to the treatment of diseases which promotes, enhances or replace body’s own inherent reparative potential. Regenerative medicine evolved from early work of many pioneers who were instrumental in the development of engineered biomaterials that replace or stimulate the reparative property of the diseased tissue
- Regenerative medicine therapies are enabled by a diverse array of products that replace, enhance or stimulate body’s reparative property. These products include cellular, gene modified cells (ex vivo gene therapy). viral and non viral vectors (in vivo therapy), biomaterial/scaffolding, small molecule*, ex vivo tissue engineered organs, or it could potentially be based on biologically secreted and extracted products and synthetic antisense oligonucleotides, peptides of all sizes which are regulated under different regulatory pathways.
- Regenerative medicine therapies include but may not be limited to what is described in the FDA regulatory documents referenced in this document.
*Small molecule that promotes regeneration of pancreatic islet cells in type I diabetic patients (https://www.ncbi.nlm.nih.gov/pubmed/15892681).
1) 21st Century Cures Act regenerative medicine therapy is defined in paragraph 8:
‘‘(8) DEFINITION.—For purposes of this section, the term ‘regenerative medicine therapy’ includes cell therapy, therapeutic
tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, except for those regulated solely under section 361 of the Public Health Service Act and part 1271 of title 21, Code of Federal Regulations.’’