A survey of the composition, safety, efficacy and regulation of non-autologous biologic treatments in human musculoskeletal pathologies

Abstract

Commercialized non-autologous biologics are produced from a variety of human tissues and are intended to treat a wide range of musculoskeletal pathologies. This survey focuses on non-autologous biologic products that are delivered via the topical or percutaneous (i.e., injected) routes. The regulatory framework established in the USA will be reviewed, including an assessment of specific categories of non-autologous biologics with their intended uses, since regulatory compliance of a specific composition or physical form of a non-autologous biologic is tightly linked to its advertised use. Guidance is provided on how to manage emerging products whose regulatory status might be unclear. Clinical safety and efficacy for non-autologous biologics for wound and burn care, including minimally processed placental products in sheet form as well as bio-engineered viable cell composite products, are well established, although efficacy tends to be wound type-specific. Micronized placental tissue products have been investigated in treating osteoarthritis of the knee and hip, and for plantar fasciitis, but require large-scale clinical studies and remain to be approved by the United States Food and Drug Administration (USFDA). Several emerging types (secretomes, exosomes) of non-autologous biologics are well documented in pre-clinical studies, but human studies are lacking. There are no Phase 3 studies reported on a secretome-based product, while there is just one Phase 3 clinical trial on-going for a bone marrow progenitor cell derived exosome product that is being used to treat acute respiratory distress syndrome. There has been substantial progress in the commercialization of exosome-based products, with studies in treating musculoskeletal pathologies a priority. Progress has been made in assessing the treatment of osteoarthritic knees and discogenic low back pain with cultured progenitor cells. However, utility and safety of these investigational products remains to be determined.

Keywords

Biologics / placenta / young plasma / allogeneic cells / wounds / burns / lower back pain / osteoarthritis

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