Around The Globe

Harmonized Tools for Clinical Trial Regulation in Africa
AVAREF Update Based on 2018-2020 Strategic Plan

David Mukanga
Senior Program Officer Regulatory Affairs, Africa Systems
Bill and Melinda Gates Foundation


n increasing number of sponsors is targeting Africa to conduct clinical trials, especially for diseases endemic to the continent, e.g., malaria, tuberculosis, diarrhea, and visceral leishmaniasis.

The African Vaccine Regulatory Forum (AVAREF), a network of National Regulatory Authorities (NRAs) and national Ethics Committees (ECs) on the African continent, was established in 2006 by the World Health Organization to strengthen the regulation of clinical trials with the support of different partners. However, the assessment of various NRAs led by the World Health Organization (WHO) with the global benchmarking tool revealed that different NRAs are at different maturity levels. This heterogeneous regulatory landscape presents regulatory challenges for sponsors willing to conduct clinical trials in the continent.

To recognize the pressing health needs on the continent, the mandate of the African Vaccine Regulatory Forum (AVAREF) was extended beyond clinical trials for vaccines to ALL medical products subject to clinical trials (and not only vaccines) in line with its 2018-2020 strategic plan. To facilitate the review and monitoring of clinical trials in the continent, AVAREF established technical working groups on clinical trials and good clinical practice (GCP) inspections. The clinical trials working group (CTWG) has developed standardized templates for the submission and assessment of clinical trials applications in the continent. The CTWG is composed of experts representing NRAs and ECs from Burkina Faso, Ghana, Kenya, Malawi, Nigeria, Uganda, and Zimbabwe. Under the framework of the German Global Health Protection Programme, the VaccTrain Team at the Paul Ehrlich Institut has lent technical support to the CTWG since February 2018. This collaboration is in line with the AVAREF’s 2018 2020 strategic plan and recommendations from the International Conference of Drug Regulatory Authorities (ICDRA) 2016. The GCP inspections working group worked with a WHO consultant to develop a clinical trials inspection guide and a checklist for GCP inspections in the continent, which will be put forth for adoption at the next AVAREF Assembly in 2019.

In the initial stage, the CTWG compiled and reviewed templates to assess clinical trial applications, i.e., quality, nonclinical, clinical, and clinical trial application forms used by reference African NRAs and other international NRAs. This process was in line with the recommendations from ICDRA 2016 where low- and medium-income countries were encouraged to follow the models used by well established international NRAs for phase 1 through 3 clinical trials.

The harmonized clinical trial application form and assessment templates were further discussed by the Technical Coordinating Committee, and endorsed by the Steering Committee at the AVAREF’s fifth meeting in September 2018. The documents agreed upon at the meeting will be used for the submission and assessment of clinical trial applications and GCP inspections. They include the following:

These harmonized templates will be tabled at the next AVAREF’s Assembly, currently anticipated to be convened between May and July 2019, for adoption. The purpose is to have all the 55 African member states adopt and incorporate them into their battery of tools for the evaluation of clinical trial applications, including emergency preparedness. Adoption of these documents by African NRAs will promote standardized clinical trial applications and assessments, and advance ongoing harmonization initiatives in the continent. This will ultimately lead to the countries meeting AVAREF’s timeline of 60 working days to review and approve or reject clinical trials.

Once these documents are finalized, it is envisioned that they will be shared with the different regional economic communities for local implementation and published on the AVAREF website. It is also planned to use these templates for all future joint reviews of clinical trials applications coordinated by AVAREF. The overarching goals are to improve the regulatory systems, to accelerate the development of safe and efficacious medical products in Africa, to reduce mortality and the burden of epidemics, and to improve quality of life.