Speeding Access to Vaccines and Medicines in Low- and Middle-Income Countries: A Case for Change and a Framework for Optimized Product Market Authorization

Abstract

BackgroundThe United Nations Millennium Development Goals galvanized global efforts to alleviate suffering of the world’s poorest people through unprecedented public-private partnerships. Donor aid agencies have demonstrably saved millions of lives that might otherwise have been lost to disease through increased access to quality-assured vaccines and medicines. Yet, the introduction of these health interventions in low- and middle-income countries (LMICs) continues to face a time lag due to factors which remain poorly understood.Methods and FindingsA recurring theme from our partnership engagements was that an optimized regulatory process would contribute to improved access to quality health products. Therefore, we investigated the current system for medicine and vaccine registration in LMICs as part of our comprehensive regulatory strategy. Here, we report a fact base of the registration timelines for vaccines and drugs used to treat certain communicable diseases in LMICs. We worked with a broad set of stakeholders, including the World Health Organization’s prequalification team, national regulatory authorities, manufacturers, procurers, and other experts, and collected data on the timelines between first submission and last approval of applications for product registration sub-Saharan Africa. We focused on countries with the highest burden of communicable disease and the greatest need for the products studied. The data showed a typical lag of 4 to 7 years between the first regulatory submission which was usually to a regulatory agency in a high-income country, and the final approval in Sub-Saharan Africa. Two of the three typical registration steps which products undergo before delivery in the countries involve lengthy timelines. Failure to leverage or rely on the findings from reviews already performed by competent regulatory authorities, disparate requirements for product approval by the countries, and lengthy timelines by manufacturers to respond to regulatory queries were key underlying factors for the delays.ConclusionsWe propose a series of measures which we developed in close collaboration with key stakeholders that could be taken to reduce registration time and to make safe, effective medicines more quickly available in countries where they are most needed. Many of these recommendations are being implemented by the responsible stakeholders, including the WHO prequalification team and the national regulatory authorities in Sub-Saharan Africa. Those efforts will be the focus of subsequent publications by the pertinent groups.

The cost of entry: An analysis of pharmaceutical registration fees in low-, middle-, and high-income countries

“…Ahonkhai and colleagues recently documented significant variations and delays in the time to final approval by regulatory agencies in Sub-Saharan Africa. [ 5 ] They argue that such barriers to timely product entry could be reduced through regulatory systems optimization, including relying on findings from reviews and inspections performed by trusted regulatory authorities, including WHO prequalification activities, to inform their own national regulatory decisions.…”

Drug manufacturing and access to medicines: the West African story. A literature review of challenges and proposed remediation

“…This makes planning and projecting difficult for the pharmaceutical companies. "A typical lag of 4-7 years has been recorded between first regulatory submission to a well-resourced NMRA and final approval in sub-Saharan Africa" (Ahonkhai et al 2016). Lengthy, indeterminate and tortuous registration times are one of the reasons why companies are reluctant in supplying medicines to certain African countries.…”

The African Medicines Regulatory Harmonization Initiative: Progress to Date

“…Marketing authorisation (MA) and clinical trials authorization (CTA) for global health products such as vaccines and medicines in many low-and middle-income countries (LMICs) have experienced delays ranging from 4-7 years in comparison to most of high-income countries (HICs) [1]. In Africa, barriers causing these delays include weak or non-coherent regulatory standards and requirements among countries; lengthy medicine registration processes that lead to delays in approval decisions; technical capacity and capability; overall resource constraints; and failure to leverage regulatory review activities already performed by better-resourced regulatory authorities and the World Health Organization (WHO).…”

“…In Africa, barriers causing these delays include weak or non-coherent regulatory standards and requirements among countries; lengthy medicine registration processes that lead to delays in approval decisions; technical capacity and capability; overall resource constraints; and failure to leverage regulatory review activities already performed by better-resourced regulatory authorities and the World Health Organization (WHO). In addition, delays in CTA have been largely attributed to the lack of role clarity and transparency between national medicines regulatory authorities (NMRAs) and national ethics committees (NECs) [1] .…”

“…Reports in SADC and ECOWAS regions revealed similar results with varying comprehensiveness of legal frameworks between countries which in turn affects the capacity to effectively regulate the market [8,9,10] . The inconsistency between regulatory frameworks and procedures within RECs and within the African region more broadly imposes further burdens on both innovator and generic pharmaceutical manufacturers, who face the added expense of adapting MA requirements to the particularities of different countries [1] . The implication of these findings is that there's not only an efficiency loss for manufacturers and registrants of medicines, but there is also considerable and inefficient efforts duplication by over-burdened NMRAs, resulting in delays that ultimately impact on patient health [1] .…”