The Implementation of a Risk-Based Assessment Approach by the South African Health Products Regulatory Authority (SAHPRA)

Abstract

Background An extensive backlog of pending regulatory decisions is one of the major historical challenges that the South African Health Products Regulatory Authority (SAHPRA) inherited from the Medicine Control Council (MCC). Revising and implementing new regulatory pathways is one of the strategic mechanisms that SAHPRA employs to circumvent this problem. Objectives To alleviate the backlog, the use of a new review pathway termed the risk-based review on the scientific quality and bioequivalence assessments was explored. The objective of the study was to articulate the risk-based assessment (RBA) pathway, to determine robust criteria for the classification of the levels of risk for medicines, and to define the improved process to be followed in the assessment and approval of medicines. Methods In 2015, an extensive exercise was conducted by SAHPRA to identify the unknown status of in-process applications. The RBA pilot project commenced in 2016 and further piloted in 2021 using the knowledge gained from the 2016 study for optimisation of efficiency. Results By 2015 the backlog was quantified as 7902 applications in the pre-registration phase. The 2015 project entailed two phases. The initial phase was conducted to identify the status of 3505 in-process applications, which resulted in the registration of 198 applications. The second phase commenced in 2016 on 4397 applications not yet reviewed whereby the RBA approach was explored. With the developed criteria for risk classification and refined end-to-end registration process, the pilot resulted in a finalisation time with a median value of 90 calendar days and a median approval time of 109 calendar days. The throughput of the RBA pilot study conducted in 2021 was 68 calendar days finalisation time for the 63 applications used. These finalisation times are lower in comparison to the 501 calendar days for the current process employed by SAHPRA for the backlog clearance programme initiated in 2019. Both the 2016 and 2021 studies had similar approval times calculated from the date of allocation of scientific assessments. The reported evaluation timelines for both studies were within 6–7 h for a low-risk quality assessment, 9–10 h for a high-risk quality assessment, 7–8 h for a bioequivalence assessment, and 2–3 h for a biowaiver and initial response assessment. Conclusions The refined processes used in the risk-based pilot studies to alleviate the SAHPRA backlog are described in detail. The process managed a reduction of the finalisation time to 68 calendar days in comparison to 501 calendar days for the current process that was employed by SAHPRA for the backlog clearance programme initiated in 2019. The RBA approach, therefore, reduces the finalisation and approval times for quality and bioequivalence assessments for regulatory authorities without compromising on the quality, safety and efficacy of the medicinal products. In addition...

Understanding medicine access strategies for innovative medicines registered in South Africa

“…The quantitative results indicate that a limited number of innovative medicines were available during the time period studied. Between 2010 and 2020, the SAHPRA faced challenges inherited from the Medicines Control Council (MCC), the chief of which was the revision and implementation of new regulatory pathways [10]. By 2018, SAHPRA had up to 8220 applications, with a median approval time of approximately 5 years [10].…”

Regulatory registration timelines of generic medicines in South Africa: Assessment of the performance of SAHPRA between 2011 and 2022

“…In the RBA process, once the detailed assessment reports were received from the evaluators, the When Available poll [23] was used to determine the most suitable time for each weekly peer review session. The reports were compiled into meeting documents and uploaded on Google Docs [24] well in advance (5-7 days) to allow evaluators to provide their comments during peer review [22]. The peer review meeting sessions were then held and only specific points of discussion, highlighted by the peer review panel, were discussed.…”

“…As a result of the abovementioned drawbacks, approximately 20% of the applications were legible for the reliance pathway and the rest had to be subjected to full review. The RBA model is intended to deal with wellknown generic applications that do not qualify for reliance review [22]. In-depth discussions are made for each stage of the registration process to identify obstacles and root causes of the backlog and how they were addressed by the RBA strategy to expedite the registration process.…”

“…RBA employed meticulous and thorough monitoring of each stage of the process as well as strategies to refine and reduce the review timelines. The implementation of the risk-based approach by SAHPRA is extensively reported on by Moeti and colleagues [22]. The report includes the evaluation timelines which are lower compared to the two processes detailed above.…”

“…The When Available poll [23] was used to determine the most suitable time for each peer review session based on the evaluators' availability. The reports were then compiled into meeting documents and uploaded on Google Docs [24] well in advance (5-7 days) to allow evaluators to provide their comments [22]. The living document would then show all comments in real-time, allowing all evaluators to see each other's comments and refer to the electronic version of the dossier on the regulatory agency reviewing software, EURSNext, when required.…”