Guidance, Recommendations and Best Practices Publications and Workshops
The FNIH has worked and will continue to work with stakeholders and collaborators to support the development of best practices guidance and recommendations to inform gene drive research, development, testing and implementation for use by funders, regulators, policy makers and international organizations as appropriate.
- To initiate, organize and facilitate development and publication of guidance, recommendations and best practices for gene drive research stakeholders.
- Bill & Melinda Gates Foundation*
- Open Philanthropy Project*
*Provided financial or in-kind support to this program.
Guidance and Recommendations
- Guidance on stakeholder engagement practices to inform the development of area-wide vector control methods. PLOS Neglected Tropical Diseases, April 25, 2019
The FNIH sponsored a three-day workshop in November 2017 in Reston, VA that brought together bioethicists and stakeholder engagement practitioners (see Agenda and Participant List) to discuss recommendations for stakeholder engagement and informed consent for interventions intended to operate at the community level as is the case for many vector control tools, including gene drive. The workshop resulted in this paper that offers teams involved in the development of area-wide vector control methods with recommendations on how to design community and stakeholder engagement programs as part of their development pathway.
- Defining the characteristics of a candidate gene-drive modified mosquito product
Gene drive technologies are being pursued for control and elimination of malaria, which is transmitted by mosquitoes. Strategically, the method of biased genetic inheritance that gene drive systems provide may be used to reduce mosquito numbers or alter mosquito ability to transmit the parasite. Proof of principle for gene drive mosquito products has been achieved in laboratory settings and additional studies are underway to prepare for field testing. An essential part of this preparation process is the development of a Target Product Profile (TPP) that defines the characteristics of a candidate gene drive-modified mosquito product that would make it suitable for field testing. Given that gene drive-modified mosquitoes are anticipated to persist for some time in the environment, defining the preferred efficacy characteristics of the product is fundamental to considerations of potential benefits vs. risks.
The FNIH has planned a series of workshops to convene a wide range of experts who can speak to the various considerations for TPP development. This project is in progress; however, once it is completed the outcomes (including points of consensus and divergence) will be made public.
Februrary 25-26, 2019, London, UK Purpose: To discuss efficacy characteristics that a gene-drive-modified mosquito (to be used for malaria control and elimination in an African setting) should meet before moving forward to field testing. Agenda and Participant List
May 6-7, 2019, Irvine California Purpose: To discuss consensus recommendations on data required to support an application for field testing of a gene drive mosquito in Africa and design of laboratory and insectary studies needed to obtain the required data. Agenda and Participant List
- Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group. James, et al., Am. J. Trop. Med. Hyg., 98(Suppl 6), 2018.
- Using Gene Drive Technologies to Control Vector-Borne Infectious Diseases. James S., Tountas K H.. Sustainability 10(12), 4789. 2018.
- Symposium Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination in Sub-Saharan Africa, ASTMH Annual Meeting, October 30, 2018 in New Orleans, LA USA.
The FNIH organized a multi-disciplinary international working group of experts to develop consensus recommendations for the safe and ethical testing of gene drive technology on mosquitoes as tools to reduce the burden of malaria transmission in Africa. The authors propose a pathway for the responsible development of gene drive products, from initial discovery research to implementation, to inform researchers, funders, regulators and other government authorities, policy makers and international organizations.
- Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values, National Academy of Sciences, Engineering and Medicine, June 2016. The FNIH co-commissioned with the National Institutes of Health this report, which provides recommendations for the conduct of responsible research on applications of gene drive technologies for public health, ecosystem conservation, agriculture as well as for basic research uses.
- Guidance Framework for Testing of Genetically Modified Mosquitoes. World Health Organization, 2014. The FNIH collaborated with the World Health Organization to develop this guidance framework, which aims to foster quality and consistency among processes for testing and regulating new genetic technologies by proposing standards of efficacy and safety testing comparable to those used for trials of other new public health tools.
- Guidance for Contained Field Trials of Vector Mosquitoes Engineered to Contain a Gene Drive System: Recommendations of a Scientific Working Group. Benedict, et al., Vector-Borne and Zoonotic Diseases, 8:127, 2008. The FNIH organized a scientific working group of experts to create guidance that aims to aid researchers, government authorities and community leaders as they consider the design and implementation of field trials to assess the safety and efficacy of genetic strategies for reducing the transmission of diseases by mosquito vectors.
- Principles for Gene Drive Research. Emerson, et al., Science, 358 (6367):1135-6,2017. The guiding principles for sponsors and supporters of gene drive research were developed by public and private sector organizations involved in sponsoring or supporting gene drive research. They describe the organizations’ commitment to mobilize and facilitate progress in gene drive research and development by supporting efforts of the highest scientific and ethical quality, inspiring a transparent approach and backing existing biosafety measures. To be considered as a signatory to these guiding principles, click here.
Risk Analysis Activities
- Results from the Workshop "Problem Formulation for the Use of Gene Drive in Mosquitoes". Roberts, et al. AM. J. Trop. Med. Hyg., 96(3):530-533,2017. In May 2016, the FNIH hosted a workshop (Agenda, Participant List and Workbook/Case Studies) with global scientific and regulatory experts to systematically evaluate the potential risks associated with the use of gene drive mosquitoes intended to reduce the burden of malaria in Africa. During the workshop, participants undertook a problem formulation exercise, focusing on gene drive mosquitoes as a method for control of the malaria vector Anopheles gambiae in Sub-Saharan Africa. Participants discussed how relevant protection goals and hazards may help to inform risk assessments of investigational gene drive organisms, the design of gene drive research and future guidelines and regulations on the use of the technology. The published consensus points describe a systematic evaluation of hazards associated with the potential use of gene drive modified mosquitoes as a new tool for reducing the burden of malaria in Africa.
- Problem Formulation Consultations for gene drive mosquitoes designed to reduce malaria transmission in Africa: results from four regional consultations 2016-2018: Teem et al. Malaria Journal. 18 article: 347. 2019. The New Partnership for Africa's Development (NEPAD), the implementing agency of the African Union, held workshops in Accra, Ghana (October 2016); Nairobi Kenya (June 2017); Gaborone, Botswana (June 2017); and Libreville, Gabon (February 2018), bringing together representatives from regional biosafety and health regulatory authorities to discuss the concept of gene drive mosquitoes as a public health tool for reducing transmission of vector borne diseases. The FNIH provided facilitation support, through a contract with the ILSI Research Foundation which has expertise and experience in such facilitation activities, and attended the workshops. The participants were presented with background information on mosquito biology, ecology and role in malaria transmission, as well as technical information on genetic engineering and gene drive function. Informative precedents from biocontrol, genetically modified crops and medicines were reviewed. In addition, participants undertook an exercise in identifying potential hazards associated with this research, and in discussions on the applicability of regional harmonization in evaluating this technology.
- Risk Assessments: The FNIH aims to ensure impartial oversight of research on genetically modified mosquitoes through support of risk assessments conducted by qualified experts having no vested interest in the success of the product. Risk assessments commissioned to date:
- Anopheles gambiae biology consensus document: Risk assessment of genetically modified organisms (GMOs) is a structured, scientific process that aims to consider the likelihood of harm to animals, humans, and the environment when undertaking prescribed activities involving such organisms in a given environment. This process involves the identification of hazards inherent to the GMO, mapping the causal linkage between these hazards and a harmful outcome, the likelihood of occurrence of such a harm, the consequence of a harmful outcome, and the level of concern related to the occurrence of the harm for the intended use in the prescribed context. As an early step in the risk assessment process, it is critical to choose a suitable organism against which the GMO will be compared to identify and characterize any features (physical, biological, behavioral etc.) stemming from the modification that could be deemed to be a hazard. Typically these comparators are the unmodified, parental version or some closely related strain that exists in the release environment. In order to assist in the environmental risk assessment of products of modern biotechnology the Organisation for Economic Cooperation and Development (OECD) Environment Directorate through its Environment, Health and Safety Division Working Group on Harmonization of Regulatory Oversight of Biotechnology prepares and makes public Consensus documents on species of interest that detail technical information such as the taxonomy, morphology, life cycle, reproductive biology, genetics, ecology, and interactions with other species and the environment. These documents provide crucial information on characteristics of the unmodified organisms that can be use as a baseline for comparison during hazard identification and initial scoping exercises The FNIH is facilitating the development of an Anopheles gambiae biology consensus document through a collaboration with the African Biosafety Network of Expertise, the ILSI Research Foundation, and the OECD Working Group. Once completed, the final Consensus document will be made public by the OECD .
Gene Drive Stakeholder Workshops
An Introduction to Regulatory Considerations for Moving Research from the Laboratory to Field Trials: Advancing from laboratory research to development of a product, and eventually to widespread use requires regulatory approval from designated national government oversight agencies. However, knowledge about how national and international regulatory frameworks work is not widely shared among researchers or institutional review committees. To address this knowledge gap for the further development of genetically engineered organisms, the FNIH held a workshop on November 19, 2019 at the Gaylord National Resort & Convention Center, National Harbor, MD, USA. Workshop speakers shared their knowledge of regulatory considerations and issues for conducting field trials, including investigational genetically engineered organisms and their derived products for applications in public health, agriculture, and protection of the environment. The workshop, designed for those who have limited experience with regulatory processes, provided an introduction to the fundamentals of regulatory science and decision-making procedures (in the US and internationally). Participants learned of the differences in goals and approaches between research science and regulatory science, about frameworks within which regulators work, and the utility of understanding regulatory needs and requirements and engaging regulatory systems early in the product development process.
In general, research science explores novelty in order to expand scientific knowledge and understanding, whereas regulatory science produces information needed to satisfy regulatory requirements and to provide product-specific evidence usually in support of safety and efficacy to support decision makers. While both have the similar goal of addressing critical needs, they have different standards for achieving quality and accountability. Those concerned with these pathways should start interacting early in the product development process to ensure that the final product meets the need and complies with local, national, and international guidelines and regulations. Risk assessment is one important regulatory science activity associated with obtaining approval to field test (or implement), and workshop participants got a taste of a small part of the risk assessment process through an interactive session on problem formulation. Workshop participants also heard from four product developers about their personal experiences with regulators and regulatory systems internationally. These speakers encouraged participants to engage regulatory systems in the country where they will be working early on during the laboratory research stage to ensure that an acceptable and useful product is developed. Agenda Participant List
Talking About Gene Drive: Communications Workshop: The FNIH organized a one-day workshop in November 2017 in Baltimore, MD attended by more than 70 researchers conducting or interested in gene drive research for public health, conservation and agriculture applications. The workshop was designed to create a forum for participants to think collectively about how to discuss gene drive technology productively with the public.
Round Table Discussion, Malaria control in Africa through genetic modification of malaria vectors: On October 11, 2016 the African Academy of Sciences and the FNIH co-hosted a roundtable discussion in Nairobi, Kenya on the use of gene drive technology for malaria control. A group of about 20 scientists from across Africa with expertise in infectious diseases, entomology and public health participated in the meeting. Discussions focused on approaches to decrease the number of malaria-carrying mosquitoes in Africa. Meeting participants raised questions on safety and efficacy aspects of the technology. Participants also noted the importance of initiating engagement activities with various diverse groups of stakeholders early in the research and development process. Given the potential for transboundary movement of gene drive-modified mosquitoes, all participants agreed that early engagement at the regional level should be a priority. Finally, participants discussed the opportunities and challenges that new technologies, such as gene drive, create for African scientists and institutions. Technology transfer and capacity strengthening (scientific and regulatory) were seen as essential to ensure successful development, testing, and, if appropriate, implementation of gene drive products, and African leadership in these activities was emphasized as critical.
Planning the First Releases of Gene Drive Mosquito Products - Site Preparation: On June 4, 2018, the FNIH convened a meeting at its office with researchers developing mosquito gene drive products, vector biologists, regulatory experts and ethicists/social scientists. The attendees discussed the criteria for deciding on the site of the first open release of a mosquito gene drive product, the results of a survey of experts asked to assess the relative importance of various scientific, regulatory and social/ethical/community criteria for site selection, as well as current outstanding needs that should be met before such a release would be feasible. The meeting outcomes included 1) recognition of the need for additional consideration of monitoring and surveillance needs and requirements (entomological, environmental and epidemiological); 2) recognition of the need to further explore the issue of liability and accountability associated with gene drive trials in Africa and whether trial insurance will be feasible; and 3) identification of need for gene drive mosquito containment guidelines that could form the basis of a facility certification process in Africa. The FNIH will publish the results of the survey, it will convene workshops that will explore trial design and monitoring needs associated with open field trials of gene drive-containing mosquitoes in Africa. Agenda
Insect Containment Accreditation Workshop: On December 6-7, 2018, the FNIH convened a meeting at its office with international experts to consider the state of current regulations, guidelines and recommendations for the containment of genetically modified (GM) insects, and the value and feasibility of establishing a third-party accreditation entity that could support institutions making risk assessments and containment decisions. The major outcomes of the meeting were: 1) Recognition that the development of insect GM technologies demand careful consideration of containment requirements to avoid premature or unplanned releases; 2) Technology has outpaced some regulations and guidance documents relevant to GM insect risk assessment and containment. A joint effort providing containment guidance by multiple respected professional entomological societies might be well equipped to ensure the expanded guidelines have broad applicability and; 3) A neutral third-party entity for insectaries and insectary management programs analogous to the institutional animal care and use accreditation entity could have value to institutions. Moving forward, the FNIH plans to engage with several organizations to explore their interest in participating in the creation of a broad set of insect containment guidelines that can enhance the ability of institutions and investigators to make good decisions and demonstrate their commitment to conducting research involving genetic technologies safely and responsibly. Agenda A Cross-Sectional Survey of Biosafety Professionals Regarding Genetically Modified Insects. O’Brochta, et al. Applied Biosafety: Journal of ABSA International, DOI: 10.1177/1535676019888047
Gene Drive-Mosquito Monitoring and Surveillance: A Scenario-Driven Workshop: On April 24-26, 2019 the FNIH convened a meeting of experts in Washington, D.C., to explore the monitoring and surveillance needs associated with various phases of open-field testing of gene drive-containing mosquitoes in Africa. The goals of this meeting were to assess the level of readiness with respect to knowledge and technologies relevant to entomological monitoring associated with gene-drive-containing Anopheles mosquitoes in Africa and to identify and define knowledge and technology gaps. The meeting participants examined and stress-tested current knowledge and technologies against four entomological monitoring and surveillance gene drive scenarios. The meeting revealed that as the scope and scale of trials increases there will be a need to employ rapid, inexpensive ‘point of care’- like technologies to meet the volume of sampling anticipated. While there is some research and development specifically on simple and rapid mosquito genotyping technologies, additional efforts will be necessary to meet the needs of gene drive mosquito programs. As the scale of trials increases the design of the trial and entomological monitoring plans interact significantly making the simultaneous consideration of both essential. The FNIH plans to continue to explore gene drive mosquito monitoring and surveillance needs through future meetings by using more specific and realistic scenarios that will be explored in much greater detail. Agenda
1st FNIH Course of Gene Editing Technologies and Their Application in the Life Sciences and Medicine in Africa:The FNIH held this workshop on June 20 – 22, 2019 at the International Centre for Insect Physiology and Ecology (ICIPE) in Nairobi, Kenya. This course provided an opportunity for established researchers and academics to extend their professional expertise by obtaining a rigorous understanding of “gene editing technologies” and their underlying mechanisms. Notable applications of these technologies with direct relevance to Africa such as their use to create “gene drive” systems as potentially powerful tools in the fight to eradicate malaria, crop improvement and gene therapy were studied. This course was the first in a series to be offered over the next four years that are intended to strengthen the capacity of African scientists to participate in discussions regarding the use of contemporary genetic technologies to address challenges to the health and welfare of Africans. Agenda