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Table 1 Issues in applying existing review and approval processes to clustered regularly interspersed short palindromic repeats (CRISPR)-mediated genome editing

From: Key challenges in bringing CRISPR-mediated somatic cell therapy into the clinic

Approval pathway Issues to be resolved
Drugs and medical devices Medical products generally go through some form of pre-market assessment to demonstrate clinical utility, safety, and efficacy. Many jurisdictions have developed adaptive licensing schemes including “fast track” approval, hospital exemptions, and compassionate use provisions that permit accelerated access to innovative treatments where they address unmet clinical need. These schemes can be invaluable in building up an early evidence base for promising but disruptive interventions, as many clinical CRISPR applications are likely to be, but at present there is little coordination across jurisdictions about the criteria to access these schemes or recognition of the evidence they generate.
Medical procedures There is ambiguity over whether CRISPR-mediated genome-editing technology is characterized as a medical product or procedure. This means it is unclear whether pre-market approval is required or whether, like surgical procedures, early assessment should be governed by domestic professional societies and institutional funding.
Patient-tailored precision therapies The high variability of biological manufacturing processes, where each batch can effectively be considered a separate product, and the individual patient-focused nature of many cell and gene therapies challenges the reliance on large-scale double-blind, placebo-controlled randomized controlled trials as the most relevant model for producing evidence of clinical safety and efficacy. A significant issue for CRISPR is whether patient-specific CRISPR constructs would each require separate approval or whether constructs with common characteristics can be treated as a group.
Exempted products Not all medical products require regulatory approval. The exemption of human tissues and cells collected from patients and returned to them after ex vivo treatment is one example. This exemption could, at least theoretically, extend to certain CRISPR applications.
Public versus private funding Different levels of protection may apply depending on whether the application is being developed by a publicly or privately funded institution. In the United States, for example, submission of gene therapy proposals to the recombinant DNA advisory committee (RAC) is only mandatory for research conducted at institutions receiving National Institutes of Health funding. For gene therapy at private institutions, submission to the RAC is voluntary. As public–private consortia become common tools for facilitating translational medicine, hard regulatory boundaries between public and private actors are likely to stifle innovation rather than secure safety.
Technology-specific regulation Many nations have specific regulatory requirements for research involving transfer of genes (e.g., the RAC in the United States, and the Office of the Gene Technology Regulator in Australia). Designed to respond to technological capabilities as they existed at the point of enactment, these laws do not necessarily address the demands of fast-paced developments. In Europe, for example, there is confusion as to whether CRISPR-engineered organisms count as “genetically modified organisms”. Different European Union Member States classify clinical gene therapies as either “contained use” or “deliberate release” of a genetically modified organism, meaning the same procedure can be subject to different interpretations of the same European Union rules in different territories.