Four Food and Drug Administration draft guidance documents and the REGROW Act: A litmus test for future changes in human cell- and tissue-based products regulatory policy in the United States?

Abstract

Modern regenerative medicine research has expanded well past the development of traditional drugs and medical devices with many promising new therapies encompassing an increasingly diverse range of substances, notably cell‐based therapies. These substantial recent developments and the progress in the health care and therapeutics fields necessitate a new regulatory framework agile enough to accommodate these unique therapies and acknowledge their differences with traditional pharmaceuticals. In the United States, recent proposed changes in the regulatory framework for autologous human cells, tissues, and cellular and tissue‐based products (HCT/Ps) and their perceived risk–benefit analysis for patients remain controversial in the scientific field. To provide perspective on of the current status of the most recent attempts to redefine and conceptualize these changes in the United States, we will examine 4 draft guidance documents implemented by the Food and Drug Administration in interpreting relevant concepts and terminology pertaining to HCT/Ps: the Bipartisan Policy Center think tank report, “Advancing Regenerative Cellular Therapy: Medical Innovation for Healthier Americans,” the proposed REGROW Act for HCT/Ps, and the current 24 Food and Drug Administration‐approved HCT/Ps and related products in the United States.

A Worldwide Overview of Regulatory Frameworks for Tissue-Based Products

“…39 HCT/Ps are subdivided in three categories of products: low-risk products, middle-risk products, and high-risk products. 40 Low-risk products are intended for current medical practice (such as blood transfusion and organ transplant). Middle-risk products include all those that fulfill all the criteria established in 21 CFR 1271.10 (a) 40 : (i) being minimally manipulated [according to 21 CFR 1271.3(f)]; (ii) being only applied for a homologous use; (iii) not being combined with other articles, and either; (iv) (a) not showing a systemic effect and being independent upon the cells' metabolic activities for its primary function or (b) showing a systemic effect and being dependent upon the cells' metabolic activities for its primary function, only when it is intended for an autologous or allogeneic use in a first-or second-degree relative.…”

“…41 Under the regulatory framework of the United States of America, minimal processing is defined: (i) in a structural tissue, as a manipulation that does not alter the tissue's relevant features implied on the repair, reconstruction, or replacement of the same and (ii) in a nonstructural tissue, as a manipulation that does not alter the tissue's relevant biological features. 39 Both low-risk and middle-risk products are also referred as ''361 HCT/Ps,'' 40 which do not require any premarket approval. These products are subjected to regulations of Section 361 of the Public Health Service Act (PHSA) and under 21 CFR 1271 to control communicable diseases.…”

Trends in Decellularized Extracellular Matrix Bioinks for 3D Printing: Inspiring a new Kind of Medicine

“…Regenerative medicine using 3-D printing of extracellular matrix with stem cells is an increasing viable option to repair and replace diseased and damaged tissues such as cartilage. Collagen matrix combined with chondrocytes, marketed as matrix-associated autologous chondrocyte implantation (MACI), was approved by the FDA for knee cartilage defects [2,6,206]. The use of decellularized ECM for cartilage treatment is hindered by the need for compact cartilage tissue.…”

“…In addition, stem cell tourism in countries where regulatory oversight is relaxed or absent continues unabated. Several discussions have taken place on the topic of stem cell and ECM use in regenerative medicine applications, with hope that in future therapies and products shown to be safe can be approved without delay [6,226]. One area that might require expedited approval is the use of autologous stem cells and ECMs [2].…”

“…The focus has been on scaffolds that help restore function over time. One limiting factor for regenerative medicine and tissue engineering applications has been the slow approval of regenerative medicine and tissue engineering therapies and constructs [6,7]. Thus, though the investment in regenerative medicine and tissue engineering has been incredible, the returns in terms of safe and reliable therapies and constructs have been slow.…”