Identifying and costing common gaps in Central and West Africa pharmaceutical regulation.

Background: Regulatory systems strengthening is crucial for catalyzing access to safe and effective medical products and health technologies (MPHT) for all. Identifying and addressing common regulatory gaps through regional approaches could be instrumental for the newly incepted African Medicine Agency. Aims: This original study sheds light on common gaps among 10 national regulatory authorities (NRAs) and ways to address them regionally. Objectives: The study used NRA self-assessment outcomes to identify common gaps in four critical regulatory pillars and estimate the cost of addressing them from regional perspectives that aimed at raising the maturity level of regulatory institutions. Methods: A cross-sectional study, using the WHO Global Benchmarking Tool (GBT), was conducted between 2020 and 2021 with five NRAs from ECCAS and ECOWAS member states that use French and Spanish as lingua franca. Results: The 10 NRAs operated in a non-formal-to-reactive approach (ML1-2), which hinders their ability to ensure the quality of MPHT and respond appropriately to public health emergencies. Common gaps were identified in four critical regulatory pillars-good regulatory practices, preparedness for public health emergencies, quality management systems, and substandard and falsified medical products-with overall cost to address gaps estimated at US$3.3 million. Contribution: We elaborated a reproducible method to strengthen regulatory systems at a regional level to improve equitable access to assured-quality MPHT. Our bottom-up approach could be utilized by RECs to address common gaps through common efforts.

Clinical and regulatory development strategies for Shigella vaccines intended for children younger than 5 years in low-income and middle-income countries.

Shigellosis causes considerable public health burden, leading to excess deaths as well as acute and chronic consequences, particularly among children living in low-income and middle-income countries (LMICs). Several Shigella vaccine candidates are advancing in clinical trials and offer promise. Although multiple target populations might benefit from a Shigella vaccine, the primary strategic goal of WHO is to accelerate the development and accessibility of safe, effective, and affordable Shigella vaccines that reduce mortality and morbidity in children younger than 5 years living in LMICs. WHO consulted with regulators and policy makers at national, regional, and global levels to evaluate pathways that could accelerate regulatory approval in this priority population. Special consideration was given to surrogate efficacy biomarkers, the role of controlled human infection models, and the establishment of correlates of protection. A field efficacy study in children younger than 5 years in LMICs is needed to ensure introduction in this priority population.

Vaccine Licensure in the Absence of Human Efficacy Data.

Clinical vaccine development and regulatory approval generally occurs in a linear, sequential manner: Phase 1: safety, immunogenicity; Phase 2: immunogenicity, safety, dose ranging, and preliminary efficacy; Phase 3: definitive efficacy, safety, lot consistency; and following regulatory approval, Phase 4: post-marketing safety and effectiveness. For candidate filovirus vaccines, where correlates of protection have not been identified, and phase 2 and 3 efficacy of disease prevention trials untenable, large and/or protracted, each trial may span decades, with full licensure expected only after several decades of development. Given the urgent unmet need for new Marburg virus and Ebola Sudan virus vaccines, the Sabin Vaccine Institute hosted a key stakeholder virtual meeting in May 2021 to explore the possibility of licensure by use of an "animal rule-like" licensure process, based on a risk/benefit assessment specific to regional needs and informed by epidemiology. This may be appropriate for diseases where there are no or limited treatment options, and those prone to sporadic outbreaks with high rates of transmission, morbidity, and mortality. The discussion focused on two contexts: licensure within the Ugandan regulatory environment, a high burden country where Ebola vaccine trials are ongoing, and licensure by the United States FDA-a well-resourced regulatory agency.

Meeting report: WHO consultation on accelerating Lassa fever vaccine development in endemic countries, Dakar, 10-11 September 2019.

At the time of writing in 2019, there have been 754 confirmed cases of Lassa fever in Nigeria, 21% of whom have died. Lassa is on the priority pathogen list for WHO's R&D Blueprint for Action to Prevent Epidemics. In September 2019, WHO convened 67 scientists, regulators, ethicists, public health officials, funders and vaccine developers to discuss the end-to-end clinical development plan for Lassa fever vaccines. The substantial increases in vaccine trial capacity in Africa were reviewed, together with lessons learned from the evaluation of vaccines against HIV, TB, malaria, and Ebola in Africa. Participants agreed on a pathway for Lassa vaccine trial progression, as outlined in WHO's Lassa fever R&D roadmap and the WHO Lassa fever Target Product Profile. Two Phase 1 trials of Lassa vaccines have already started, and it was agreed that continuing interactions between high income and African regulatory and ethics authorities and WHO will be important in progression towards Phase 2b/3 efficacy trials in Lassa fever endemic areas. There was agreement that, for diseases whose burden is mainly in Africa, it should be the norm that African regulatory authorities are consulted on trial design/progression before first-in-human Phase 1 trials. Phase 2b-3 vaccine trial capacity needs to be in place in high Lassa fever burden areas where efficacy trials will take place. Licensure of one or more Lassa fever vaccines suitable for West African populations is a realistic goal in the next 5 years, with CEPI and WHO aligned on the pathway forward for vaccine development.

[Epidemiology and risk factors for voluntary intoxication in Mali]. / Épidémiologie et facteurs de risque des intoxications volontaires au Mali.

INTRODUCTION: Voluntary intoxication is a major medical and social problem in developing countries and the most common method of suicide attempt. The purpose of this paper is to describe the main characteristics of voluntary intoxication in Mali and the risk factors associated with the outcome of poisoning. More generally, the aim is to contribute to the reduction of morbidity and mortality associated with self-poisoning. METHODS: We conducted a retrospective descriptive study of the cases of deliberate self-poisoning recorded between 2000 and 2010 in 15 Malian hospitals. RESULTS: 884 cases of self-poisoning (233 men and 651 women) were identified during the period of study, representing 28% of all cases of poisoning reported during this period. The mean age of the victims was 23 ± 8.9 years. The available data indicate that the most common cases were suicide attempts and self-induced abortion using toxic substances (respectively 62.8% and 29% of all cases). The most common methods were drugs (74.5%), especially chloroquine (65%), followed by industrial products (9.1%). The most commonly used industrial products were hydrochloric acid (26.7%), sodium hypochlorite (bleach) (22.2%) and sulphuric acid (15.6%). The findings suggest that poisoning symptoms vary depending on the type of substance, the amount ingested and the delay before treatment. 86 of the 877 cases with known outcome resulted in death. CONCLUSION: The number of cases of poisoning is probably underestimated since many cases remain undiagnosed and unreported.

Assessment of the impact of market regulation in Mali on the price of essential medicines provided through the private sector.

OBJECTIVE: In 1998, the government of Mali adopted a national pharmaceutical policy aimed at promoting a supply system for generic essential medicines that would guarantee equal access for all citizens. Distribution and delivery is a shared responsibility of both public and private sectors (wholesalers and pharmacies). To influence private sector behaviour, the national policy uses a combination of government regulation and market forces. In 2006, the government issued a decree fixing maximum prices in the private sector for 107 prescription drugs from the national list of 426 essential medicines. The current study assessed the impact of this intervention on the evolution of market prices (wholesale and retail), and the subsequent availability and public access to essential medicines in Mali. METHODS: A cross-sectional descriptive survey was conducted in February and May 2006, and January 2009, with 16 wholesalers and 30 private drugstores in Bamako, Mali. RESULTS: The overall availability of essential medicines at private wholesalers (p=1) and pharmacies (p=0.53) was identical before and after the enforcement of the 2006 decree fixing maximum drug prices. Contrary to concerns expressed by wholesalers and pharmacies, and the other stakeholders, the decree did not impact negatively on availability of essential medicines. In fact, median wholesale prices in 2009 were 25.6% less than those fixed by the decree. In private pharmacies, retail prices were only 3% more expensive than the recommended prices, compared with being 25.5% more expensive prior to enforcement of the decree. CONCLUSIONS: The study shows that prices of essential medicines in Mali have evolved favourably towards the prices recommended by the government decree. Further, the study contributes to mounting evidence that market regulation by governments does not necessarily negatively affect drug availability; in fact, given the reduction in prices, the study shows that Malians arguably have better access to more affordable essential medicines.

Joint reviews and inspections: strategic forms of collaboration for strengthening the regulatory oversight of vaccine clinical trials in Africa.

Vaccine developers are required to submit a clinical trial application to the authorities in each country where a clinical trial will be conducted. The application has to be made both to the relevant Ethics Committees and to the National Regulatory Authorities, and only after appropriate clearance by both can a clinical trial commence. This paper describes two specific strategies, joint reviews of vaccine clinical trial applications and joint inspections of clinical trial sites by groups of countries, as part of a WHO initiative to strengthen capacity for the regulatory oversight of clinical trials in Africa. Significantly, the joint reviews and inspections contributed to reinforcing the capacities of the regulatory authorities as well as defining an efficient process to maximize the quality of the reviews and minimize undue delays. Finally we will suggest complementary mechanisms to overcome the potential limitations of joint reviews and inspections.

Regulatory oversight of clinical trials in Africa: progress over the past 5 years.

Randomized controlled clinical trials represent the best way to establish the therapeutic or preventive value of medicines. This decade has seen a strong shift in the location of clinical trials from industrialized countries to developing countries, including many in Africa. However, without independent strong regulatory and ethical oversight of clinical trials the safety of research subjects, and scientific integrity of clinical data cannot be verified. This article draws up a portrait of clinical trials regulation in Africa in support of development of priority medicines, highlights challenges and presents the progress made by countries under WHO guidance over the past 5 years.

Factors influencing the utilization of research findings by health policy-makers in a developing country: the selection of Mali's essential medicines.

BACKGROUND: Research findings are increasingly being recognized as an important input in the formation of health policy. There is concern that research findings are not being utilized by health policy-makers to the extent that they could be. The factors influencing the utilization of various types of research by health policy-makers are beginning to emerge in the literature, however there is still little known about these factors in developing countries. The object of this study was to explore these factors by examining the policy-making process for a pharmaceutical policy common in developing countries; an essential medicines list. METHODS: A study of the selection and updating of Mali's national essential medicines list was undertaken using qualitative methods. In-depth semi-structured interviews and a natural group discussion were held with national policy-makers, most specifically members of the national commission that selects and updates the country's list. The resulting text was analyzed using a phenomenological approach. A document analysis was also performed. RESULTS: Several factors emerged from the textual data that appear to be influencing the utilization of health research findings for these policy-makers. These factors include: access to information, relevance of the research, use of research perceived as a time consuming process, trust in the research, authority of those who presented their view, competency in research methods, priority of research in the policy process, and accountability. CONCLUSION: Improving the transfer of research to policy will require effort on the part of researchers, policy-makers, and third parties. This will include: collaboration between researchers and policy-makers, increased production and dissemination of relevant and useful research, and continued and improved technical support from networks and multi-national organizations. Policy-makers from developing countries will then be better equipped to make informed decisions concerning their health policy issues.