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P224: Evaluation of New Medicines in SAHPRA’s Backlog Clearance Project: The Impact of Reliance on Regulatory Performance

Poster Presenter

Lorraine Danks

Regulatory Systems Strengthening Consultant
Bill & Melinda Gates Foundation
South Africa

Objectives

To determine the impact of reliance review pathways on CMC, bioequivalence & clinical review timelines of NCEs and generic molecules in the South African Health Products Regulatory Authority, with reference to full and abridged reviews using unredacted Recognized Regulatory Authority assessments.

Method

Review metrics were analyzed for CMC and clinical/bioequivalence (BE) for new medicine applications in SAHPRA’s Backlog Project using both full and abridged review pathways, as well as the assessors’ feedback on efficiency. Additionally, the impact of reliance on GMP compliance was assessed.

Results

The study hypothesized that assessment timeframes for new product applications following a reliance-based review would be shorter than those subjected to a full review of the data. It provides a comparison between full and abridged review timelines for NCEs and generic products in SAHPRA’s Backlog Clearance Project (01 August 2019–31 December 2022). The study also evaluated the differences in SAHPRA’s scientific review and sponsor response times for all products in view of the two assessment pathways. In terms of NCEs, a comparison between the Recognized Regulatory Authority (RRA)- and SAHPRA-approved labelling was conducted as a measure of true reliance implementation. Furthermore, focus group discussions were held with SAHPRA’s assessors regarding their feedback on effectiveness and efficiency of the implementation of the abridged review pathway. The results for the NCE applications were: as for the CMC, SAHPRA clock stop time was 91 days (abridged) versus 179 days (full) (p<0.001); the sponsor clock stop time was 34 versus 105 days, respectively (p<0.001); and there was greater than a 2-fold time reduction when CMC was finalized via the abridged versus full review route (125 vs 284 days; p<0.001); in terms of clinical, there was a 99 day decrease in total clinical data approval time through an abridged review (230 vs 329 days; p=0.027); and a decrease in marketing authorization time for NCEs assessed in an abridged manner (446 vs 619 days; p=0.0005). The results for the generic applications were: as for the CMC and BE, SAHPRA clock stop time was 97 days (abridged) versus 191 days (full) (p<0.001); the sponsor clock stop time was 26 days (abridged) versus 81 days (full) (p<0.001); and there was greater than a 2-fold time reduction when CMC and BE were finalized via the abridged versus full review pathway (122 vs 272 days) (p<0.001). The results clearly support the hypothesis set at the outset.

Conclusion

In terms of NCEs, both SAHPRA’s CMC and clinical abridged reviews were shorter than those of the matched full review pathway products. There was a time-reduction associated with abridged reviews across all measured timeframes whether it was time spent by SAHPRA on scientific assessment, sponsors providing responses to the agency’s queries or total review time. The results showed that the implementation of abridged review was less successful for clinical assessment, partly due to an additional review step for clinical data, whereby review outcomes are also presented for endorsement by an Advisory Clinical Committee, which only meets at certain intervals. Misalignment between RRA- and SAHPRA-approved labelling was also found, which further resulted in delayed approvals. There was, however, still a time reduction compared to full review despite this. Consequently, marketing authorization timelines were significantly shorter for NCEs that underwent both CMC and clinical abridged review. Similar trends were observed when analyzing CMC and BE review timelines for generic product applications. Less than half the time was required to assess and approve CMC and BE data in generic product applications via an abridged review pathway and sponsors were able to provide responses in one third of the time. Both NCE and generic product data showed comparability in terms of timeframes for abridged versus full CMC review. Lastly, reliance on the Pharmaceutical Inspection Co-operation Scheme and RRA Certificates of GMP Compliance when assessing the GMP status of sites was found particularly effective in reducing marketing authorization timelines. The conclusions drawn from these results confirm the time-saving benefit of implementing reliance review practices within SAHPRA. The lessons learnt from SAHPRA’s Backlog Clearance Project could help other agencies in emerging economies to streamline their regulatory performance, with commensurate increased access of medicines to patients.