AVAREF FAQs
AVAREF Facts
Q. What is AVAREF and how is it related to WHO?
A. AVAREF was founded by the WHO in 2006 to serve as a platform for connecting National Regulatory Authorities (NRAs) and National Ethics Committees (ECs) across Africa, committing to build technical, institutional, and professional capacity through collaborative broad partnerships and harmonization. The AVAREF Secretariat is part of the WHO Regional Office for Africa and focuses its work on supporting clinical trials in Africa, notably through harmonization of technical and process requirements, as well as through the joint reviews of multi-country clinical trial applications.
Q. How is AVAREF managed?
A. AVAREF has four bodies that manage its strategic and operational functions: The AVAREF Assembly, AVAREF Steering Committee, AVAREF Technical Coordination Committee, and the AVAREF Secretariat. In 2019, the AVAREF Assembly adopted a new governance structure to align with the African Medicines Regulatory Harmonization (AMRH) Initiative. This new structure transformed AVAREF’s Technical Coordination Committee into a Continental Working Group, and the AVAREF Steering Committee was re-established as an Advisory Committee to provide strategic guidance for the Working Group Committees. AVAREF is in the process of implementing this new governance structure. A detailed description of these bodies is provided below.
Q. Who funds AVAREF?
A. AVAREF is currently funded by the Bill & Melinda Gates Foundation. Previous funding has come from the European Union (through the European and Developing Countries Clinical Trials Partnership – EDCTP), and the Government of Canada (through the Canadian HIV Vaccine Initiative). Other partners that provide in-kind support to the work of AVAREF include the U.S. Food and Drug Administration, European Medicines Agency, Coalition for Epidemic Preparedness Innovations, and the Paul Ehrlich Institute, Germany.
Q. Which countries are members of AVAREF?
A. All 55 African countries are eligible to become members of AVAREF, provided they commit to subscribe to the principles and goals of AVAREF. Regional Economic Communities (RECs) are associate members of AVAREF, while regulatory agencies (from outside Africa), industry associations, product development partnerships, NGOs, donors, researchers, and any other relevant stakeholders can be admitted as observers. The Secretariat collaborates closely with colleagues in the WHO Eastern Mediterranean Region (EMRO) and in collaboration with AUDA-NEPAD and the African Medicines Regulatory Harmonisation (AMRH) initiative to fully include all African countries.
Q. How does a country benefit by being part of AVAREF?
A. Countries benefit from being a part of AVAREF by receiving the information, scientific knowledge, training and best practices that are shared among Member States, and which enable the countries to make informed decisions regarding authorization and inspection of clinical trials for all medical products, as well as for the evaluation of registration of dossiers for vaccines in the region. AVAREF provides opportunities for training, mentorship and external expertise as needed to countries for review and authorization of clinical trial applications.
Q. Does AVAREF fund clinical trials or product development?
A. No, AVAREF does not fund clinical trials. However, there are many WHO partners who fund clinical trials and AVAREF can provide some information in this area, upon request.
Membership, Newsletter and Webinars
Q. How does one become a member of AVAREF?
A. To become a member of AVAREF, interested parties can send an email to the Secretariat based at WHO AFRO to request a membership application and guidelines at afrgoavaref [at] who.int.
Q. How can I receive the AVAREF Newsletter?
A. AVAREF usually publishes its newsletter by email listserv twice a year. In 2020, AVAREF is publishing its newsletter every quarter to share updated information and to better respond to events surrounding the COVID-19 pandemic. To receive the AVAREF Newsletter, contact us at afrgoavaref [at] who.int to request to be added to the listserv, or simply click here to subscribe.
Q. How can I attend AVAREF webinars?
A. AVAREF hosts webinars to share current information on global regulatory response to COVID-19, development of COVID-19 therapeutics and vaccines, and to deepen the understanding of the AVAREF emergency joint review process, among other important topics. Webinar participants include national regulators and ethics committee members, vaccine developers, sponsors, scientists and researchers. Interested parties can contact the AVAREF Secretariat to be added to the AVAREF email listserv at afrgoavaref [at] who.int. All members will automatically receive invitations to AVAREF webinars. You can also check out information on upcoming webinars and events on our website here.
Q. How many African countries belong to AVAREF? Are there plans to expand membership to other categories of national agencies?
A. All 55 Member States of the African Union are Member States of AVAREF. Engagement initially began with 19 members and subsequently grew to 23 countries in the WHO African Region, before finally covering all countries on the continent. Further collaboration of the WHO African Regional Office with the Eastern Mediterranean (EMRO) region will increase and improve contributions of North African countries to the AVAREF platform.
Clinical Trial Applications
Q. What is a joint review?
A. Joint reviews bring together National Regulatory Authorities and Ethics Committees from multiple countries in order to collectively review a common clinical trial application. This process actively involves the sponsor and is facilitated by AVAREF, which contacts all national authorities, organizes and facilitates meetings, sets timelines and standardizes the review process, and provides support to national authorities to execute the review.
Q. What are the different types of joint reviews and how do the timelines differ for each?
A. There are three types of joint reviews: Normal/Regular, Expedited, and Emergency.
- Normal/Regular reviews target a timeline of 60 working days from submission to country decisions
- Expedited reviews target a timeline of 30 working days from submission to country decisions
- Emergency reviews target a timeline of 10 or 15 working days from submission to country decisions
Q. What are the criteria for an application to be deemed eligible for an expedited or emergency joint review?
A. Expedited reviews are normally reserved for products which aim to fulfil an unmet medical need, whereas emergency reviews are currently reserved for COVID-19 therapeutics. Please refer to the AVAREF guidelines for more information.
Q. What are the advantages of joint reviews for clinical trial applications?
A. Joint reviews offer several advantages to sponsors. These include:
- Unified and harmonized review steps and processes
- Support provided by AVAREF in facilitating the process and engaging national authorities
- Inclusive meetings with all trial countries
- A centralized Q&A process, with all countries having the opportunity to raise queries at pre-determined stages in the review
- In most cases, faster decisions than would have been possible by following individual national procedures
Q. How can a sponsor notify AVAREF of interest in conducting a multi-country joint review?
A. Sponsors are requested to initiate contact with the AVAREF Secretariat by filling in the “Intention to Submit” form here and submitting this to the AVAREF Secretariat via email [afrgoavaref [at] who.int] at least one month before the clinical trial application process is expected to commence. For more information, please reach out directly to AVAREF afrgoavaref [at] who.int.
Q. How many joint reviews has AVAREF coordinated?
A. AVAREF has coordinated more than 10 joint reviews since its creation. While the joint review activity of the platform was limited in its first 10 years, as the process proved its effectiveness, more developers have submitted clinical trial applications through AVAREF in the past few years. AVAREF has supported joint reviews with a diversified scope, including anywhere from 2 to 15 target countries per clinical trial application. With the COVID-19 pandemic, AVAREF is advertising the platform widely to all developers willing to conduct trials in Africa, and communicating member countries’ readiness and availability to receive clinical trial applications. Our goal is to ensure that as many developers as possible are aware of the benefits of conducting more clinical trials in Africa, especially with the new AVAREF emergency joint review process.
Q. Do African countries allow first-in-human clinical trials for vaccines?
A. Yes. One of the first clinical trials for Ebola vaccine candidates—a first-in-human phase I clinical trial – took place in Mali and Kenya in 2015. The AVAREF Secretariat is committed to supporting African countries that wish to host first-in-human clinical trials.
Q. How is AVAREF supporting community preparedness for clinical trials?
A. The AVAREF platform ensures that regulators and ethics committees are able to comprehensively address all aspects of a clinical trial application (CTAs), as well as any issues relating to or emerging from clinical trials. This includes community engagement and any community- or population-specific matters. Similar considerations were addressed in past CTA joint reviews and AVAREF is committed to providing countries with the required technical advice and support to overcome any challenges that may arise during clinical trials. AVAREF, in partnership with the Bill & Melinda Gates Foundation, is well prepared to address this component of preparedness and to improve clinical trial outcomes.
Q. Where can I find guidance on submitting a phase III clinical trial application?
A. You can find both the guidance documents and data requirements for submission of all clinical trial applications on the AVAREF website.
Joint Review Process for Clinical Trials
Q. Does AVAREF charge a fee for the services it provides during joint reviews?
A. No, the AVAREF Secretariat does not charge a fee for its services. However, the national ethics committees and regulatory authorities have their own fee schedules for clinical trial application reviews. Please refer to individual country websites for more information.
Q. In the event that a sponsor plans to carry out a clinical trial for a COVID-19 product in a single country, is it still possible to use the emergency review procedure (as opposed to multi-country trials)? And can AVAREF assist in the review of that clinical trial application?
A. Yes, the emergency process and timelines apply to all African countries and can be used even if a trial is carried out in a single country. AVAREF can assist the country by coordinating and using what is called an assisted review, which involves inviting another country (including both the national regulatory authority and ethics committee) to participate in a joint review of the same application. This type of review requires the agreement of a clinical trial application recipient country. The process can assist the recipient country especially when the country has limited experience in reviewing clinical trial application with newly developed vaccines or medicines. The same emergency process and timelines will apply.
Q. Is a parallel (regulatory and ethics) review a mandatory requirement in the emergency joint review process? If so, for countries having sequential reviews in their national regulations and as their practice, how can this requirement be met? How can countries with sequential review processes deal with such a situation?
A. To minimize delays, the AVAREF emergency joint review process requires parallel submission to both ethics committees and regulators. If a country’s regulatory process does not allow parallel submissions, that country must still find internal ways to adhere to and meet the agreed upon emergency joint review timelines. The AVAREF Secretariat is supporting countries as they switch from sequential to parallel submissions and reviews.
Q. For a multi-country trial with single protocol, if few of the countries agree to participate while others do not, is there any way to resolve the blockage for protocol approval?
A. In such a case, the AVAREF Secretariat will agree to share outcomes (including queries raised and the sponsor’s answers) of the review with non-participating countries to avoid duplication of work.
The AVAREF Secretariat engages all the countries involved in the joint review to ensure that there is alignment on the agreed timelines and processes. The Secretariat is responsible for following up with all stakeholders of the joint review until decisions are made.
Q. Is there any provision for joint inspections of clinical trial sites after CTA approval?
A. Usually countries will conduct their own good clinical practice (GCP) inspections of trial sites. However, AVAREF has conducted joint inspections for multi-country clinical trials, starting with the 2006 joint inspections of the conjugate meningitis vaccine clinical trial sites. More recently, a joint GCP inspection was undertaken in Ethiopia to pilot a new GCP inspection guide and checklist developed by AVAREF.
Q. Can AVAREF support developers in identifying local submission and administrative requirements as well as contacting local authorities for clinical trial applications in Africa?
A. Yes. At the start of each joint review, countries are contacted by AVAREF to share their local submission and administrative requirements as well as to nominate a focal point for the review. This information is shared with the sponsor and will also be collectively discussed by all stakeholders in the pre-submission meeting in order to ensure full alignment of all parties involved.
Q. Does AVAREF play a coordinating role in the licensure process in the product approval phase?
A. Yes. AVAREF supports Member States for joint reviews for product registration in public health emergencies and if the product was approved for clinical trials through an AVAREF joint review. For more information, please refer to the AVAREF Guidelines here.
Other AVAREF Services
Q. What are the services offered by AVAREF to developers?
A. AVAREF can support developers with many aspects related to clinical trials. Specifically, this includes:
- Scientific advice tailored to specific platforms, vaccines, and medical products
- Orchestration of meetings including the sponsor and regulators/ethics committees from each trial country
- Alignment of deadlines and support to countries to achieve shorter review timelines in case of emergency
- Arrangement and facilitation of multi-country joint reviews for clinical trials in Africa
- Information about in-country technical and process/administrative requirements for filing CTAs with NRAs and ECs
Q. What are the services offered by AVAREF to national authorities (National Regulatory Authorities, National Ethics Committees, Institutional Review Boards, etc.)?
A. AVAREF commits to sharing information, scientific knowledge, training and best practices with national authorities. This is part of the commitment to build technical and institutional capacities in Member States. Further, AVAREF promotes harmonization by encouraging the standardization of regulatory processes, sharing of information, and transparency through collaborative partnerships between Member States. AVAREF also coordinates joint reviews, bringing together national authorities of multiple countries to review clinical trial applications, which participate in capacity building, process improvements and collaboration.
Q. After a Phase III trial is complete and we enter the product approval phase, will AVAREF play a coordinating role in the licensure process?
A. Yes. During public health emergencies and other situations outlined the AVAREF guidelines as well as in the AVAREF Compassionate Use Guide, the AVAREF Secretariat is ready to support Member States with the technical advice they require to perform joint reviews for product registration.
Q. Do you have a list of documents readily available for submission of a Phase III application?
A. Yes. You can find both the guidance documents on submission and the data requirements here. For further information, and to access the list of documents on our website. You can also email us at afrgoavaref [at] who.int for further information.
Q. Apart from facilitating submissions and approvals, does AVAREF also identify potential sites for clinical trials or provide contract research organization (CRO) services?
A. No, AVAREF does not formally provide CRO services or identify clinical trial sites. However, the AVAREF Secretariat can certainly draw on the rich expertise of our membership if suggestions are needed, and recommends that product developers leverage the Clinical Trial Community platform on the African Academy of Sciences website. This platform provides developers with information on clinical trial sites, principal investigators and CRO services, and aims to be fully operational in the final quarter of 2020. For more information on this platform, please reach out to Caxton Murira [c.murira [at] aasciences.africa] or contact the AVAREF Secretariat for help at afrgoavaref [at] who.int for further assistance.