Preparing an Insectary in Burkina Faso to Support Research in Genetic Technologies for Malaria Control.

The Institut de Recherche en Sciences de la Santé (IRSS) of Burkina Faso, West Africa, was the first African institution to import transgenic mosquitoes for research purposes. A shift from the culture of mosquito research to regulated biotechnology research and considerable management capacity is needed to set up and run the first insectary for transgenic insects in a country that applied and adapted the existing biosafety framework, first developed for genetically modified (GM) crops, to this new area of research. The additional demands arise from the separate regulatory framework for biotechnology, referencing the Cartagena Protocol on Biosafety, and the novelty of the research strain, making public understanding and acceptance early in the research pathway important. The IRSS team carried out extensive preparations following recommendations for containment of GM arthropods and invested efforts in local community engagement and training with scientific colleagues throughout the region. Record keeping beyond routine practice was established to maintain evidence related to regulatory requirements and risk assumptions. The National Biosafety Agency of Burkina Faso, Agence Nationale de Biosécurité (ANB), granted the permits for import of the self-limiting transgenic mosquito strain, which took place in November 2016, and for conducting studies in the IRSS facility in Bobo-Dioulasso. Compliance with permit terms and conditions of the permits and study protocols continued until the conclusion of studies, when the transgenic colonies were terminated. All this required close coordination between management and the insectary teams, as well as others. This article outlines the experiences of the IRSS to support others undertaking such studies. The IRSS is contributing to the ongoing development of genetic technologies for malaria control, as a partner of Target Malaria. The ultimate objective of the innovation is to reduce malaria transmission by using GM mosquitoes of the same species released to reduce the disease-vectoring native populations of Anopheles gambiae s.l.

Auditing Preparedness for Vector Control Field Studies.

The value of baseline entomological data to any future area-wide release campaign relies on the application of consistent methods to produce results comparable across different times and places in a stepwise progression to larger releases. Traditionally, standard operating procedures (SOPs) and operational plans support this consistency and, thus, the validity of emergent data. When release plans include transgenic mosquitoes for vector control or other novel beneficial insects, additional factors come into play such as biosafety permits, stakeholder acceptance, and ethics approval, which require even greater coordination and thoroughness. An audit approach was developed to verify the correct use of SOPs and appropriate performance of tasks during mosquito mark, release, recapture (MRR) studies. Audit questions matched SOPs, permit terms and conditions, and other key criteria, and can be used to support subsequent "spot check" verification by field teams. An external team of auditors, however, was found to be effective for initial checks in this example before the use of a transgenic strain of laboratory mosquitoes. We recommend similar approaches for field studies using release of novel beneficial insects, to ensure useful and valid data as an outcome and to support confidence in the rigor of the step-wise process.

Maintaining Quality of Candidate Strains of Transgenic Mosquitoes for Studies in Containment Facilities in Disease Endemic Countries.

Transgenic mosquitoes are being developed as novel components of area-wide approaches to vector-borne disease control. Best practice is to develop these in phases, beginning with laboratory studies, before moving to field testing and inclusion in control programs, to ensure safety and prevent costly field testing of unsuitable strains. The process of identifying and developing good candidate strains requires maintenance of transgenic colonies over many generations in containment facilities. By working in disease endemic countries with target vector populations, laboratory strains may be developed and selected for properties that will enhance intended control efficacy in the next phase, while avoiding traits that introduce unnecessary risks. Candidate strains aiming toward field use must consistently achieve established performance criteria, throughout the process of scaling up from small study colonies to production of sufficient numbers for field testing and possible open release. Maintenance of a consistent quality can be demonstrated by a set of insect quality and insectary operating indicators, measured over time at predetermined intervals. These indicators: inform comparability of studies using various candidate strains at different times and locations; provide evidence of conformity relevant to compliance with terms of approval for regulated use; and can be used to validate some assumptions related to risk assessments covering the contained phase and for release into the environment.

Studies of Transgenic Mosquitoes in Disease-Endemic Countries: Preparation of Containment Facilities.

Novel approaches to area-wide control of vector species offer promise as additional tools in the fight against vectored diseases. Evaluation of transgenic insect strains aimed at field population control in disease-endemic countries may involve international partnerships and should be done in a stepwise approach, starting with studies in containment facilities. The preparations of both new-build and renovated facilities are described, including working with local and national regulations regarding land use, construction, and biosafety requirements, as well as international guidance to fill any gaps in regulation. The examples given are for containment categorization at Arthropod Containment Level 2 for initial facility design, classification of wastes, and precautions during shipping. Specific lessons were derived from preparations to evaluate transgenic (non-gene drive) mosquitoes in West and East African countries. Documented procedures and the use of a non-transgenic training strain for trial shipments and culturing were used to develop competence and confidence among the African facility staff, and along the chain of custody for transport. This practical description is offered to support other research consortia or institutions preparing containment facilities and operating procedures in conditions where research on transgenic insects is at an early stage.

Containment Studies of Transgenic Mosquitoes in Disease Endemic Countries: The Broad Concept of Facilities Readiness.

Genetic strategies for large scale pest or vector control using modified insects are not yet operational in Africa, and currently rely on import of the modified strains to begin preliminary, contained studies. Early involvement of research teams from participating countries is crucial to evaluate candidate field interventions. Following the recommended phased approach for novel strategies, evaluation should begin with studies in containment facilities. Experiences to prepare facilities and build international teams for research on transgenic mosquitoes revealed some important organizing themes underlying the concept of "facilities readiness," or the point at which studies in containment may proceed, in sub-Saharan African settings. First, "compliance" for research with novel or non-native living organisms was defined as the fulfillment of all legislative and regulatory requirements. This is not limited to regulations regarding use of transgenic organisms. Second, the concept of "colony utility" was related to the characteristics of laboratory colonies being produced so that results of studies may be validated across time, sites, and strains or technologies; so that the appropriate candidate strains are moved forward toward field studies. Third, the importance of achieving "defensible science" was recognized, including that study conclusions can be traced back to evidence, covering the concerns of various stakeholders over the long term. This, combined with good stewardship of resources and appropriate funding, covers a diverse set of criteria for declaring when "facilities readiness" has been attained. It is proposed that, despite the additional demands on time and resources, only with the balance of and rigorous achievement of each of these organizing themes can collaborative research into novel strategies in vector or pest control reliably progress past initial containment studies.

Experiences in Engaging the Public on Biotechnology Advances and Regulation.

Public input is often sought as part of the biosafety decision-making process. Information and communication about the advances in biotechnology are part of the first step to engagement. This step often relies on the developers and introducers of the particular innovation, for example, an industry-funded website has hosted various authorities to respond to questions from the public. Alternative approaches to providing information have evolved, as demonstrated in sub-Saharan Africa where non-governmental organizations and associations play this role in some countries and subregions. Often times, those in the public who choose to participate in engagement opportunities have opinions about the overall biosafety decision process. Case-by-case decisions are made within defined regulatory frameworks, however, and in general, regulatory consultation does not provide the opportunity for input to the overall decision-making process. The various objectives on both sides of engagement can make the experience challenging; there are no clear metrics for success. The situation is challenging because public input occurs within the context of the local legislative framework, regulatory requirements, and the peculiarities of the fairly recent biosafety frameworks, as well as of public opinion and individual values. Public engagement may be conducted voluntarily, or may be driven by legislation. What can be taken into account by the decision makers, and therefore what will be gathered and the timing of consultation, also may be legally defined. Several practical experiences suggest practices for effective engagement within the confines of regulatory mandates: (1) utilizing a range of resources to facilitate public education and opportunities for understanding complex technologies; (2) defining in advance the goal of seeking input; (3) identifying and communicating with the critical public groups from which input is needed; (4) using a clearly defined approach to gathering and assessing what will be used in making the biosafety decision; and (5) communicating using clear and simple language. These practices create a foundation for systematic methods to gather, acknowledge, respond to, and even incorporate public input. Applying such best practices will increase transparency and optimize the value of input from the public.