Since the 21st Century Cures Act was passed in December 2016, the US FDA has instated a framework for the regulation of regenerative medicine products and has plans to support and expedite the development of regenerative medicine products, including human cells, tissues, and cellular and tissue-based products (HCT/Ps). The Agency has published several guidance documents specific to the complex issues of these types of products, with the February 2019 Guidance for Industry: Expedited Programs for Regenerative Medicine Therapies for Serious Conditions providing the Agency’s recommendations on the expedited development and review of regenerative medicine therapies. A drug is eligible for regenerative medicine advanced therapy (RMAT) designation if:

1. The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using 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;
2. The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
3. Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition

Also, certain human gene therapies and xenogeneic cell products may also meet the definition of a regenerative medicine therapy based on FDA’s interpretation of Section 506(g) of the FD&C Act.

An RMAT submission request must be made either concurrently with or as an amendment to an Investigational New Drug (IND) application. The US FDA may grant or deny the RMAT designation request.

The latest information from the FDA website regarding RMAT designation requests received is as follows:

* Requests that are still pending a decision are included in the total requests received column; Data as of June 30, 2020.

As of 24 July 2020 (latest data from FDA website) there were 18 approved cellular and gene therapy products licensed by the Office of Tissues and Advanced Therapies (OTAT) within CBER. Approximately half of the approved products were allogeneic cord blood hematopoietic progenitor cell (HPC) therapy products indicated for use in unrelated donor HPC transplantation procedures. Five of the 18 products were composed of autologous cells expanded and/or further manipulated ex vivo, with three of these being CAR T immunotherapy products for the treatment of various B cell cancers. A genetically modified live attenuated virus product for the treatment of recurrent melanoma and two adeno-associated virus vector-based gene therapy products are among the approved products as well as one product that contains allogeneic human cells and human extracellular matrix proteins in a bovine collagen matrix. In addition to the various cancers noted above as well as prostate cancer, the therapeutic indications for the approved cell therapy and gene therapy products are many, including retinal dystrophy, spinal muscular atrophy, facial wrinkles, articular cartilage defects in the knee, and mucogingival conditions.

Like the above cell therapy and gene therapy products, the more than 40 RMAT designated products represent a diverse array of products to treat disorders including various cancers, metabolic disorders, immunodeficiencies, blood discresias, Parkinson’s disease, and more. Although the Agency has granted 52 RMAT awards as noted in the table above, as of 30 June 2020, none of the products had received approval yet.

As research teams develop more cellular and gene therapy products for the treatment of a wide array of medical conditions, the need for custom nonclinical and clinical programs required to support market approval of products that are based on human cells, tissues, or HCT/P will rise. And for RMAT designated products, the study designs may be substantially different from more traditional IND programs. Researchers will need to partner with experienced CROs to guide them through the development lifecycle of their product. Per the updated Guidance for Industry and Food and Drug Administration Staff – Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue Based Products: Minimal Manipulation and Homologous Use published in July 2020, the Agency announced its intent to exercise enforcement discretion through May 31, 2021 (extended from the prior guidance which had it as November 2020) under limited conditions with respect to the IND application and premarket approval (BLA) requirements, for certain HCT/Ps. Rho, Inc. has experienced scientists fully capable of providing the necessary resources to help companies get market approval for their cellular or gene therapy products, with or without RMAT designation.

Dr. Brenda Faiola, PhD, DABT, Senior Nonclinical Research Scientist, has over 15 years of experience in the pharmaceutical and medical device industries. She received her PhD in Immunology from Duke University in 2001 and has been a Diplomate of the American Board of Toxicology since 2004. At Rho, Dr. Faiola provides support regarding nonclinical aspects of Integrated Product Development and Integrated Regulatory Submissions for pharmaceutical, biologics, and medical device programs.