For many LMICs, various factors have recently affected the economic climate, most importantly the COVID-19 pandemic and the resultant lock-down periods. This has led to the sharpest economic contraction since the Great Depression in the 1930s and has exacerbated the dire economic situation in developing countries already burdened by fiscal deficits and excessive public debt [29]. Four years on from the start of the pandemic, many governments across Africa are implementing austerity measures to curb spending [30, 31]. That said, the majority of the NRAs in developing countries are dependent on government grants to operate, the notable exceptions being the Uganda National Drug Authority (NDA), the Kenya Pharmacy and Poisons Board (PPB) and the Zambia Medicines Regulatory Authority (ZAMRA), with these three agencies relying heavily on fees collected from the pharmaceutical industry [17, 18, 32]. As Ndomondo-Sigonda and colleagues further highlight, the fact that the Uganda NDA relies almost solely on application fees is a direct result of its government’s deliberate transition away from its former 100% reliance on donor funding. In contrast, the medicines regulator in Burundi depends exclusively on fiscal contributions to enable its operations [32]. To remain financially afloat, NRAs are increasingly reaching out to donor organisations to support their operations, but this funding varies significantly from country to country [32].

The weak economic growth in South Africa has impacted the flow of fiscal support to SAHPRA, with the government grant anticipated to decline by an estimated 11% over the next four years. Consequently, the authority has become more dependent on fees paid by the pharmaceutical sector. Until the end of 2024, SAHPRA only charged fees for medicines registration and lifecycle management applications (including retention fees), clinical trial applications, licence fees (for manufacturers, distributors, importers, exporters), good practice (GxP) inspections, vaccine lot release and ancillary fees for a few administrative services [19]. However, some of these tariffs are not aligned with SAHPRA expenditure for the individual activity, with the contracted NCL for vaccine testing making up 6% of SAHPRA’s annual budget, but with only a 21% cost-recovery in the 2023/2024 financial year. Given that many of the activities falling within the SAHPRA mandate do not generate fees, the current fee income stream cannot resolve its budgeting shortfalls.

The main SAHPRA expenditure relates to assessor and other authority personnel costs, followed by its operational expenditure. It is noteworthy that the majority of assessors contracted to the BCP to clear the SAHPRA application backlog were supported by external funders, as the in-agency capacity was not sufficient. The cost for these external assessors was approximately US$2,671,000 over the duration of the project, this excluding the BCP staff and SAHPRA overtime assessors’ costs. During the period 2019–2022, in parallel to these clearance efforts, SAHPRA was investing heavily in optimising its operational capacity and systems with a view of reaching WHO ML3. Many of the South African regulator’s current undertakings to maintain this status, such as defending its regulations, as well as the much-needed revision of its Medicines and Related Substances Act, maintenance of the QMS with regular audit cadences, capacitating its regulatory personnel, setting up a national system to curb substandard and falsified medical products (SFMPs), inclusive of contract laboratory testing, as well as vigilance endeavours, are not at present being compensated for by the private sector, although the latter is reaping the benefits these initiatives bring about in terms of a more securely regulated environment in which to operate and serve patients. In view of this, SAHPRA has revised its fees to ensure future financial viability and to “enhance the ability of the regulator to respond to the needs of the regulated environment”, as per the MTT recommendation [1].

With SAHPRA budget deficits in mind, research into the financial benefits of reliance implementation by SAHPRA was undertaken, with the outcome revealing a significant impact in terms of assessment duration and associated costs. The results pointed to a marked reduction in assessors’ costs for both NCE and generic new registration applications, when the CMC and/or BE data were assessed by relying on prior assessments and authorisation by medicines regulators SAHPRA trusts, with the authority conserving more than US$270,000 through this approach for the 188 product applications assessed. Investing in reliance practices not only enabled expedited medicine access, but also allowed SAHPRA to utilise its financial resources more effectively.

On further review of the fee schedules of ten selected African NRAs, it is apparent that half of these differentiate between the fees they charge for NAS and generic product assessment, with higher fees for innovator or biological product applications (the South African, Ethiopian, Tanzanian, Zambian and Zimbabwean NRAs). However, upon examining whether any of the authorities distinguished between full and reliance review when setting fees, it became apparent that only ZAMRA charges different tariffs for these types of assessments, in that it charges a reduced fee for an abridged review. Out of the reviewed NRAs, only 40% (SAHPRA, Uganda NDA, TMDA and MCAZ) have a fast-track review pathway through which applicants can theoretically, at a higher cost, receive an expedited assessment of their products. Across various industries, fast-track services are generally more expensive to ensure speedier outcomes. Two examples of WHO-Listed Authorities (WLAs) who have subscribed to this approach are the Singapore HSA in charging higher fees for a verified versus an abridged review of health product applications [33] and Swissmedic, where a procedure with prior-announcement (3–6 pre-submission notification) secures an applicant, under certain conditions, a 20% faster process but with doubled fees, as the alert allows Swissmedic to plan appropriately for the assessment of the incoming NAS application and ensure the “efficient processing of applications” [34].

Upon evaluating the industry perspectives on reliance practices and how successful implementation of these may benefit not only NRAs but also the private sector, the majority of respondents were in favour of financially incentivising NRAs to adopt reliance practices, through which NRAs could be supported on their journey to WHO ML3. They also acceded to a cost-based fee model for NRAs and/or an annual fee contributing to the expansion and maturity of individual African NRAs. Some respondents indicated that, in return, there should be a stricter observance of published timelines by NRAs. Increased trust amongst African medicines regulators and applicants, whether local or international, was also cited as a key ingredient to successful reliance implementation and the industry’s willingness to aid with the proliferation of mature NRAs on the African continent.

An ML3 NRA brings great benefit to a country, as well as to a region, in terms of safer, more efficacious medicines of good quality available to its people, but the financial and resource requisites for attaining and sustaining this status are significant. Many African NRAs are heavily dependent on their governments’ contributions to carry out agency operations, and given the current economic climate, this revenue stream has become reduced, with resources thinly spread within the NRAs. The paucity of skilled staff, directly equating to poor NRA performance outcomes, and the industry’s expectations are two sides of the same coin. However, the study results have shown reliance to be a lever for not only expediting medicine authorisation, but to, in addition, conserve the financial resources of the implementing authority. It illustrated the ROI of an NRA investing in reliance practices and, if optimally implemented, the benefits for the pharmaceutical industry and its patients.

If less financial (and human) resources are required for marketing authorisation by employing reliance mechanisms, more funds would be available to NRAs for regulatory and information system-strengthening initiatives. The redirected funds would enable advancement of country-specific activities required by the WHO, such as border control of medicines, vigilance, post-marketing surveillance and legislative overhauls. Any cost-saving would be re-invested into the regulator to not only sustain or improve the maturity level of that NRA, but also to aid improved service delivery through an increased number of expert evaluators, especially for specialised products, such as cutting-edge biological therapies, digital health technologies (DHTs) and artificial intelligence (AI)-operated medical devices, optimised and integrated data management systems, with record linkages, and accurate tracking of all the NRAs key performance indicators (KPIs).

This proposal aligns well with current global thinking on the topic. In its position paper on EMA fees, the European Federation of Pharmaceutical Industries and Associations (EFPIA) suggests tenets for a proportionate fee structure for EMA, as well as for national competent authorities (NCAs) [35], and by extension, one could argue, applicable to African NRAs. Among these principles are transparency, fairness and proportionality, and sustainability. EFPIA argues for an expanded maintenance fee for all marketing authorisations, which would cover minor variations, renewals and PV activities, and which would taper off as a product nears the end of its lifecycle [35]. Through this income, it is anticipated that a regulatory authority may be adequately funded, considering the primary costs associated with the services an NRA provides, fully cognisant of the SWOT analysis of an agency, and with a future-forward perspective. It is anticipated that a product-specific MA maintenance fee (and this does not refer to the low-cost annual retention fee currently paid by the pharmaceutical private sector) would provide an NRA with suitably skilled experts in a variety of regulatory disciplines, which would enable dynamic regulatory assessments, with continued dialogue between stakeholders throughout the assessment process [35]. However, EFPIA concludes that fees should be fair and proportionate to all stakeholders. Aligned with this approach, the IFPMA published its own position paper [36] on regional joint assessment procedures in Africa, propounding that “fees should be determined on actual costings and linked to agreed regulatory performance indicators”, with periodic agency performance reviews to justify any fee amendments. In this regard it would be important to holistically consider the overall costs of the NRA authorising the product, as disregard of this could risk the agency being financially disadvantaged in terms of reliance reviews.

As a progressive example of fee modelling, the United States Prescription Drug User Fee Act (PDUFA), which was first enacted in 1992 and now in its sixth reauthorisation, guarantees that the US FDA, in addition to the annual funding supplement from Congress, “will continue to receive a source of stable and consistent funding during fiscal years 2023–2027 that will allow the agency to fulfil its mission to protect and promote public health by helping to bring to market critical new medicines for patients” [37]. The 2024 PDUFA fee for a human medicine application requiring clinical data review was US$4,048,695 [38] and, should the product qualify for a priority review, an additional fee of US$1,314,206 was levied [39]. The PDUFA fees are not only used for medicine application evaluations, but also for facility inspections, maintenance of US FDA information databases, and other programmatic support such as research and policy development [40]. Furthermore, the US FDA does not only collect fees from industry, but also from certain accreditation and certification entities. Importantly, the tariffs are not a “fee-for-service payment” as the payments contribute to all the above activities and assist in funding the US FDA payroll and achieving its programmatic goals [40]. The US FDA fee model is an example of a holistic approach to safeguarding agency sustainability and development, but with assured deliverables, as expected by the private sector.

As a result of the manual processing of the assessors’ claims at the beginning of the project, with the COVID-19 pandemic then disrupting their processing, some of the claim information was not available. In addition, no assessment of NCE clinical evaluation was performed, as the previous study [7] concluded that clinical reliance had been less successfully implemented during the SAHPRA BCP, due to several reasons; these included a heavy reliance on external advisory committee members, with the experts exhibiting a reduced risk appetite, leading to a reticence to adopting reliance review practices. Hence, analysing these data, which showed less reliance impact on timelines, would not have contributed to the outcomes of this research. Another limitation of this study could potentially be the fact the analysis is based on data from one ML3 regulatory authority in Africa or not having included any of the ML2 authorities to carry out comparison of resource consumption use across two different maturity levels. However, since WHO GBT requirements for obtaining and maintaining ML3 is the same across the board, it is highly unlikely that having included another ML3 authority would have made any difference in the outcome of the study.