Heritable Human Genome Editing (2020) / Chapter Skim
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5 National and International Governance of Heritable Human Genome Editing
5 National and International Governance of Heritable Human Genome Editing
Pages 145-168
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From page 145... ...
However, this chapter concludes with recommendations for core components of these efforts. A RESPONSIBLE GOVERNANCE SYSTEM FOR HERITABLE HUMAN GENOME EDITING HHGE would entail a form of assisted reproductive technology (ART)
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From page 146... ...
How Heritable Human Genome Editing Would Relate to the Regulation of Gene Therapies Many somatic cell gene therapies currently undergoing clinical development rely on using genome editing technologies. Somatic cell gene therapies have a history of highly regulated oversight in the countries in which they have been carried out, including the United States, Japan, China, India, and countries in Europe.
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From page 147... ...
Engagement with Civil Society • need for discourse among civil society about human genome edit A ing. As stated by one respondent, "society must have the opportunity to shape the way in which the science develops." There are diverse levels of understanding about the meaning of scientific terms such as "genome," "somatic cell," and "germline"; what types of genome editing uses are currently being developed; and how HHGE would be undertaken should it be permitted.
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From page 148... ...
The regulatory process involves the institutional reviews required for human clinical trials as well as additional institutional oversight by biosafety committees and federal review. Federal oversight includes requirements for prospective approval from the national
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From page 149... ...
How Heritable Human Genome Editing Would Relate to the Existing Regulation of Assisted Reproductive Technologies As noted above, HHGE would constitute a form of ART, and ARTs have a very different history of regulatory oversight from that of somatic gene therapies. Laws regarding the use of ART vary substantially among countries.
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From page 150... ...
. The a United Kingdom is an example of a country that utilizes "seriousness" in its evaluation of PGT applications and where the use of IVF with PGT is permitted only to prevent specific genetic conditions that have been approved by the Human Fertilisation and Embryology Authority.
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From page 151... ...
As described in Chapter 1, the characteristics include a controlled step-wise process under the auspices of appropriate national regulators; limitation to cases involving parents wishing to have a genetically-related child unaffected by serious disease; limited licensure to use in single cases rather than blanket approval, with ongoing review before subsequent licenses are issued; a comprehensive informed consent process; long-term follow-up of offspring; and prohibition of uses beyond the permitted indication. Lessons Applicable to the Creation of an Oversight System for Heritable Human Genome Editing As with other medical technologies, an oversight system for HHGE would need to address all stages of a research and clinical translation pathway.
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From page 152... ...
The MRT Scientific Assessments Over the course of four scientific reviews, expert panels examined preclinical data on the use of MRT in model organisms and in human research embryos, scrutinizing both published and unpublished data. One of the key issues evalu ated was the ability to produce animals using MRT that had normal development and adult health, and in which mitochondria were predominantly derived from the donor egg.
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From page 153... ...
All countries in which HHGE research and clinical applications may be pursued will need regulatory mechanisms to oversee use of HHGE and impose sanctions where appropriate, as well as a clearly communicated way for concerns about possible violations of regulations to be reported. Because HHGE would be deployed within an existing culture of IVF and ART clinics, it will be important to engage with this community on the issues posed by HHGE prior to any clinical uses.
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From page 154... ...
Other countries may similarly need to wrestle with how HHGE could fit within or challenge national medical oversight systems and determine whether they need to create new oversight paradigms or whether existing oversight mechanisms could be modified to sufficiently address the oversight needs for HHGE. REQUIREMENTS FOR NATIONAL OVERSIGHT SYSTEMS FOR HERITABLE HUMAN GENOME EDITING Regardless of the details of the regulatory systems that a country may design for HHGE, national regulatory authorities or their equivalents would need to establish the specific criteria that must be met for any translational application of HHGE to proceed in their jurisdictions.
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From page 155... ...
The need to develop governance approaches to encompass HHGE provides a potential opportunity to use and develop the content of internationally recog nized human rights to influence future laws, policies, and regulatory responses around HHGE. However, the possibility of using human rights to frame, delimit, or expand concepts such as the freedom to conduct scientific research, the right of everyone to benefit from scientific advances, the right of children to the high est attainable standard of health, or even the rights of future generations has not yet been discussed by international bodies deliberating on HHGE.
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From page 156... ...
THE NEED FOR A SYSTEM OF GLOBAL COORDINATION AND COLLABORATION While countries have decision-making authority concerning the research toward, or clinical use of HHGE, it is critical to also have inter ational n scientific and ethical cooperation on HHGE. A translational pathway for HHGE therefore requires governance systems that extend beyond those of individual countries to enable transparent discussion about any approved clinical uses of HHGE and the resulting outcomes.
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From page 157... ...
Any proposed mechanism for international governance of HHGE will need to provide for at least three functions: 1. An international scientific advisory panel to provide ongoing techni cal assessment and evaluation of developments in the science and technologies on which HHGE depends and to make recommenda tions about their suitability and readiness for particular clinical uses.
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From page 158... ...
Multiple gaps in the ability to fully characterize such genome editing or assess its effects make it premature to use any HHGE approaches at the time of this writing, and articulating the essential characteristics of a translational pathway does not mean that a country should necessarily permit even initial clinical uses. There is, therefore, a need for an international advisory body to regularly review the latest scientific evidence and to evaluate its potential impact on the feasibility of HHGE.
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From page 159... ...
This combination is similar to that for Data Safety and Monitoring Boards or Data Monitoring Committees for large, often multi-site, clinical trials, which seek to ensure relevant expertise in clinical specialty areas, clinical trial methodologies and analysis, biostatistics, and often in the ethics of design, conduct, and interpretation of clinical trials.4 Because the panel would be assessing evidence that could be used to support progress toward initial use of HHGE for serious monogenic diseases, the panel would also greatly benefit from including representatives of the public, such as members of genetic disease and disability communities. 3 See www.sart.org.
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From page 160... ...
These assessments would include reviewing advances in preclinical research, providing advice on whether sufficient methodologies to support evaluating a proposed use had been developed, informing the deliberations of a country's own advisory or regulatory bodies if requested, and analyzing the outcomes of any permitted clinical uses of HHGE.
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From page 161... ...
The Commission strongly believes that successfully carrying out these functions requires more than the current informal and ad hoc systems. International Body for Evaluating and Making Recommendations before Crossing Heritable Human Genome Editing Thresholds This report has categorized possible clinical uses of HHGE according to the assessment of the potential harms and benefits they present, with a focus on initial clinical uses.
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From page 162... ...
of HHGE Societal, ethical, Development of safe legislative, and effective regulatory, and methodology and institutional preclinical evidence deliberations on to support the potential use and consideration of a International International oversight of HHGE proposed use Scientific Body Advisory Panel Country-level determination that Convene HHGE could be considered for clinical Serve as a discussions on resource a range of use for specified purpose, informed for regularly scientific and by international discussions assessing societal issues scientific and including clinical evaluating Appropriate knowledge and making approvals to proceed and preclinical recommenda to initial clinical use evidence tions concern ing crossing any threshold Monitoring and to a proposed Societal, ethical, new class of legislative, assessment of safety use of HHGE regulatory, and and efficacy including institutional preimplantation, deliberations on prenatal, and potential use and post-natal outcomes, oversight of HHGE and determination whether to proceed * Beyond Commission's remit with any further clinical uses FIGURE 5-2 International discussions would be required to determine whether it would be possible to cross significant thresholds and describe translational pathways for potential uses of HHGE.
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From page 163... ...
Making recommendations on whether it is appropriate to cross subsequent thresholds in the use of HHGE would be a key role for an international body with responsibility for convening the international debate on HHGE. Potential uses of HHGE beyond the circumstances set out by this Commission open the door to impacting reproductive options for a significantly larger group of people.
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From page 164... ...
There are also international processes that focus more on promoting responsible scientific conduct, for example, the Good Clinical Practice guidance for clinical trials developed by the International Council for H armonisation of Technical Requirements for Pharmaceuticals for umanH Use (ICH) , whose members and observers include national regulatory agencies, industry, and international organizations.6 The ICH develops its guidelines through a process that includes formation of an expert working group to draft a technical document on an issue, followed by development by regulatory members of a draft guideline.
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From page 165... ...
has a means by which anyone can report an "Alleged Anti-Doping Rule Violation or any act or omission that could undermine the fight against doping."8 Some research funders have also developed mechanisms to facilitate the investigation of complaints made against researchers they fund. CONCLUSION AND RECOMMENDATIONS The pursuit of a translational pathway toward the clinical use of HHGE would represent the controlled alteration of a human embryonic genome using genome-editing tools, offered as part of an assisted reproduction intervention.
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From page 166... ...
is being considered should have mechanisms and competent regulatory bodies to ensure that all of the following conditions are met: • ndividuals conducting HHGE-related activities, and their i oversight bodies, adhere to established principles of human rights, bioethics, and global governance; • he clinical pathway for HHGE incorporates best practices t from related technologies such as mitochondrial replacement techniques, preimplantation genetic testing, and somatic ge nome editing; • ecision making is informed by findings from independent d inter ational assessments of progress in scientific research n and the safety and efficacy of HHGE, which indicate that the technologies are advanced to a point that they could be considered for clinical use; • rospective review of the science and ethics of any applica p tion to use HHGE is diligently performed by an appropri ate body or process, with decisions made on a case-by-case basis; • otice of proposed applications of HHGE being considered n is provided by an appropriate body; • etails of approved applications (including genetic condi d tion, laboratory procedures, laboratory or clinic where this will be done, and national bodies providing oversight) are made publicly accessible, while protecting family identities; • etailed procedures and outcomes are published in peer- d reviewed journals to provide dissemination of knowledge that will advance the field; • he norms of responsible scientific conduct by individual t investigators and laboratories are enforced; • esearchers and clinicians show leadership by organizing r and participating in open international discussions on the coordination and sharing of results of relevant scientific, clinical, ethical, and societal developments impacting the assessment of HHGE's safety, efficacy, long-term monitor ing, and societal acceptability;
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From page 167... ...
The ISAP should: • rovide regular updates on advances in, and the evalua p tion of, the technologies that HHGE would depend on and recommend further research developments that would be required to reach technical or translational milestones; • ssess whether preclinical requirements have been met for a any circumstances in which HHGE may be considered for clinical use; • eview data on clinical outcomes from any regulated uses r of HHGE and advise on the scientific and clinical risks and potential benefits of possible further applications; and • rovide input and advice on any responsible transla p tional pathway to the international body described in Recommendation 10, as well as at the request of national regulators. Recommendation 10: In order to proceed with applications of heritable human genome editing (HHGE)
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From page 168... ...
168 HERITABLE HUMAN GENOME EDITING • provide a responsible translational pathway for the new class of use. Recommendation 11: An international mechanism should be estab lished by which concerns about research or conduct of heritable human genome editing that deviates from established guidelines or recommended standards can be received, transmitted to relevant national authorities, and publicly disclosed.
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