Worldwide Assessment of Low- and Middle-Income Countries' Regulatory Preparedness to Approve Medical Products During Public Health Emergencies

Abstract

Background: Regulatory preparedness for public health emergencies is critical. However, responses to past emergencies, such as the 2009 H1N1 influenza pandemic and medical product shortages, have revealed sizable gaps in countries' regulatory capacity and preparedness. A systematic analysis of the regulatory preparedness of countries around the world has not yet been performed. The purpose of this study was to analyze and document the current regulatory preparedness status, highlight the related gaps and challenges in order to propose strategic, harmonized, and sustainable regulatory solutions to improve future responses to public health emergencies.Methods: From 2016 to 2020, we used the World Health Organization (WHO)'s Global Benchmarking Tool (GBT), a standardized instrument for identifying national regulatory authorities' strengths and gaps, to analyze the regulatory preparedness of 84 Member States, 95% of which were low- or middle-income countries. We analyzed whether participating Member States had not implemented, displayed ongoing implementation, had partially implemented, or had fully implemented 10 of the GBT's 268 sub-indicators most relevant to regulatory preparedness for public health emergencies.Findings: Only 10 Member States (12%) that underwent benchmarking had fully implemented all 10 sub-indicators related to regulatory preparedness for public health emergencies; 34 (40%) had fully implemented ≥50% of the emergency sub-indicators, and 20 (24%) had not fully implemented any of the sub-indicators. With regard to individual sub-indicators, regulatory preparedness ranged from 19 Member States (23%) fully implementing reliance on clinical trial decisions of others to 45 (59%) fully implementing legal provisions to fast-track (or expedite) marketing authorization applications.Interpretation: Many WHO Member States have limited regulatory preparedness for a public health emergency. Strengthening regulatory systems and promoting Good Regulatory Practices and reliance in these countries, to enable efficient response to emergencies, should be a global health priority.

Leveraging WHO’s Global Benchmarking Tool to strengthen capacity in clinical trials oversight for public health emergencies: the GHPP VaccTrain model

“…Such indirect benefits could be capacity strengthening components in the area of infrastructure, education or training, which may altogether support continuity in research or improve regular medical care upon completion of the initial studies [ 17 ]. The limited number of countries involved in this study notwithstanding, its extension on the number of public health emergency-related sub-indicators for CTO as analyzed previously [ 7 ] is a valuable addition that strengthens the current body of knowledge on the status of emergency preparedness, particularly in LMICs. Aside the limitations in the reliance model on CT decisions of other competent NRAs during emergencies, this data further highlighted other CT regulations-related gaps as well as cracks in the adjusted procedures for expeditiously screening, evaluating and authorizing emergency-related CTs.…”

“…The lack of capacity, resources and an effective preparedness and response plan in place for disease outbreaks came to the fore after the Ebola crises in West Africa highlighted the limitations in the world’s preparedness for public health emergencies [ 8 ]. Quite recently, data from WHO benchmarking results showed the potential fragility of many member states (especially LMICs) to public health threats due to limited regulatory preparedness [ 7 ]. Particularly for CTO, a full implementation of the sub-indicator for reliance on CT decisions of others was 23%; the least percentage implementation of the regulatory functions assessed for the 84 countries included in the study [ 7 ].…”

“…Quite recently, data from WHO benchmarking results showed the potential fragility of many member states (especially LMICs) to public health threats due to limited regulatory preparedness [ 7 ]. Particularly for CTO, a full implementation of the sub-indicator for reliance on CT decisions of others was 23%; the least percentage implementation of the regulatory functions assessed for the 84 countries included in the study [ 7 ]. Our baseline data indicative of a fragile CT regulatory structure for timely approval of CTAs in our partner NRAs (all LMICs) at the inception of our capacity strengthening partnership, was therefore in consonance with these findings.…”

“…Under the circumstances, NRAs become particularly challenged to adapt to the use of specialized tools, processes and pathways to receive and expeditiously screen, evaluate, and authorize emergency-related CTs at greater speeds than regular routines. Unfortunately, however, capacity in many low- and middle-income countries (LMICs) for this pursuit is often limited and with considerable shortcomings [ 7 , 8 ]. As a corollary of this weakness, the usually expected accelerated approval processes, which advances the availability and use of new medical products, vaccines and technologies at a faster pace is often hampered.…”

The Pivotal Role of Quality Technical Structures for Clinical Trials Oversight in the Achievement of Long-Term Capacity Strengthening Outcomes

“…Data from the registry and results database ClinicalTrials.gov was further used to aid in mapping country situational reports to the differential dynamics in CTs regulated by the individual NMRAs. The contents of online-available national CT guidelines of respective countries were assessed for their compliance with internationally accepted provisions capable of supporting the documented implementation of newly gained expertise using the WHO Global Benchmarking Tool for CTO ( 30 , 31 ), similar to a recently reported endeavor for regulatory preparedness in public health emergencies ( 32 ).…”