REGULATORY AND ETHICAL ASPECTS OF ORTHOBIOLOGIC THERAPIES
Orthobiologic therapies show significant promise to improve outcomes for patients with musculoskeletal pathology. There are considerable research efforts to develop strategies that seek to modulate the biological environment to promote tissue regeneration and healing and/or provide symptomatic relief. However, the regulatory pathways overseeing the clinical translation of these therapies are complex, with considerable worldwide variation. The introduction of novel biologic treatments into clinical practice raises several ethical dilemmas. In this review, we describe the process for seeking approval for biologic therapies in the United States, Europe, and Japan. We highlight a number of ethical issues raised by the clinical translation of these treatments, including the design of clinical trials, monitoring outcomes, biobanking, "off-label" use, engagement with the public, marketing of unproven therapies, and scientific integrity.
The term “musculoskeletal regeneration” is widely considered to encompass therapeutic solutions for musculoskeletal conditions that harness the benefits of biology to improve healing, reduce pain, improve function, and provide an environment for tissue regeneration. 38 Tools to facilitate musculoskeletal regeneration include drugs, surgical intervention, physical and electromagnetic stimuli, and biologics. Orthobiologics are biological substances derived from the body that are used to treat musculoskeletal disease, injury, and disability, focusing on the growth, replacement, and repair of cells, organs, and tissues specific to the health needs of patients. 30
The potential application of regenerative therapies spans the breath of orthopaedics, using approaches such as cell transplantation, gene transfer, and tissue engineering. 31 These strategies differ significantly from most mainstream treatments in orthopaedic practice, as they aim to treat the underlying cause of the disease with the goal of augmenting the native biological repair processes, preferably at an earlier stage of the disease progression. Despite enormous promise, most orthobiologic approaches remain at a very early step along the road to widespread application. Culture-expanded autologous and allogeneic cell therapies and gene therapies have all entered human clinical trials, with many patients already treated with current Good Manufacturing Practice–produced musculoskeletal regenerative approaches. 7,63,64 While many regenerative interventions remain in preclinical phases of research, the number of clinical studies is expected to increase rapidly in the near future.
Despite research advances, there is growing concern about the increasing number of centers that are marketing stem cell–based interventions directly to consumers, making unwarranted claims, or performing risky biologic procedures. 35 Such centers and their associated providers have been known to recommend, prescribe, or deliver so-called regenerative preparations, in many cases marketed as “stem cells,” without sufficient data to support their true content, safety, and efficacy. 27,44 Although the progress of promising investigational therapies should not be thwarted, clinicians and regulators have a duty to protect the public from the risks associated with unproven and uncharacterized therapies. 32,33
An appreciation of the regulatory environment of orthobiologics and the ethical dilemmas that they raise is central to developing future strategies to support legitimate translation. However, the regulatory environment can appear both convoluted and cumbersome, with considerable worldwide variation. As such, there is a pressing need for these aspects to be deciphered and presented in a logical and accessible form. In this narrative review, we describe the current regulatory environment of orthobiologics and describe the process for seeking approval for biologic therapies using the United States, Europe, and Japan as examples of global variation. We highlight a number of ethical issues raised by the clinical translation of these treatments, including the design of clinical trials, monitoring of outcomes, biobanking, “off-label” use, engagement with the public, marketing of unproven therapies, and conflicts of interest.
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Regulatory and Ethical Aspects of Orthobiologic Therapies - PMC (nih.gov)
Published November 2022 in the Orthopaedic Journal of Sports Medicine (Volume 10 - Issue 11).