Evaluation of Commercially Available Knee Cartilage Restoration Techniques Stratified by FDA Approval Pathway

Abstract

Background: Commercially available products used in knee cartilage reconstructive and restorative surgical practices fall under unique US Food and Drug Administration (FDA) regulatory pathways that determine the level of evidence required to market each product.

Purpose: To evaluate the levels of evidence in the literature supporting commercially available cartilage repair procedures stratified by FDA regulatory pathway (section 351 vs section 361 of "Human Cells, Tissues, and Cellular and Tissue-Based Products" [HCT/P] in the Code of Federal Regulation) with the hypothesis that products requiring approval under a stringent regulatory pathway (351 HCT/P) have higher levels of evidence in the literature supporting use and that products with a less stringent regulatory pathway (361 HCT/P) have a higher number of products available for use in the United States.

Study design: Systematic review; Level of evidence, 4.

Methods: A search of the PubMed database was performed to identify all peer-reviewed articles pertaining to either allograft or autologous cartilage repair technologies. Predefined inclusion and exclusion criteria were used to find clinical, preclinical, and laboratory studies while excluding duplicates, systematic reviews, and products not available in the United States. Articles were categorized by regulatory pathway (351 and 361 HCT/P), and variables including publication year, type of publication, level of evidence, and number of publications were analyzed.

Results: After application of predefined criteria, 470 of 1924 articles were included in this study. The 351 HCT/P group was composed entirely of autologous chondrocyte implantation (ACI) technology; 94% of the 361 HCT/P group was composed of osteochondral allografts (OCA). The articles regarding 351 HCT/P were more likely to be clinical in nature than the articles on 361 HCT/P (80% vs 48%, respectively; P = .0001) and entailed significantly more level 1 studies (25 vs 0, respectively; P < .0001). Twice as many articles in the 351 HCT/P group were published in the American Journal of Sports Medicine compared with the 361 HCT/P group (71 vs 38, respectively; P = .18).

Conclusion: Both ACI and OCA have robust evidence supporting their use, whereas the remaining regulated products have little or no supporting evidence. Technologies regulated by 351 HCT/P were more likely to be level 1 clinical studies and published in the highest impact journal. The 361 HCT/P pathway regulated many more products, with fewer articles supporting their use.

Keywords: 351 HCT/P; 361 HCT/P; cartilage; knee; regulation; restoration.