Table. Summary of the Methodologies and Recommendations Informing the Development of the New Regulatory Model Based on the Principles of the WHO GBT .

Study Number	Aim	Method	Key Recommendations From the Study	Corresponding Elements Within the New Regulatory Model (Figure 2)	Corresponding GBT Parameters Endorsing the Elements of the Model
Study 17	Examine the regulatory review process applied by the MCC	A questionnaire was completed by the MCC to describe the organisation of the authority, record key milestones and timelines in the review process and to identify GRevPs	Apply a risk-based approach to the review of NASs using FRP Formalise the implementation of the QMS Define timelines and measure milestones in review process and overall approval time	The following 5 areas for improvement were identified to be common amongst the recommendations from the 6 studies conducted. These 5 elements encompass all the recommendations from each study and were deemed to be critical in informing the development of the new regulatory model	The GBT is used to evaluate each of the nine component regulatory functions of the regulatory system against a series of sub-indicators For the purpose of this study reference was made specifically to the sub-indicators of the regulatory functions of the national regulatory systems and marketing authorisation
Study 210	Provide the historical context supporting the new regulatory environment in South Africa and the transition from the MCC to SAHPRA	A review was conducted of the history of the enabling legislation supporting the establishment of SAHPRA and the similarities and differences between the MCC and SAHPRA were compared	Training and skills development of regulatory expert reviewers Establish committee structures within the NRA for ad hoc consultation Monitoring and evaluating Formalise the QMS Apply a risk-based approach to the review of NAS using FRP	Quality Measures Establish a dedicated quality management unit Formally implement QMS, GRevPs and GRelPs Codify and institutionalise the quality policy, SOPs, guidelines and assessment templates Use the UMBRA BR Summary Template as the guide for BR assessment and the outline for the preparation of the ZAPAR Employ ODMPs	RS05.01: Top management intervention is required to demonstrate commitment and leadership to develop and implement a QMS
					RS05.02: The quality policy, objectives, scope and action plans for the establishment of the QMS must be in place and be communicated to all levels
					RS05.04: Enough competent staff must be assigned to develop, implement and maintain the QMS
					RS03.05: The NRA is required to promote GRPs
					MA04.10: The formal implementation of GRevPs is required
Study 38	Evaluate the timelines of the milestones of the South African review process and the overall approval process for NASs	Data identifying the milestones and overall approval times for NASs registered by the South African Agency during 2015–2018 were collected and analysed	Define timelines and measure milestones in review process and overall approval time Formally implement GRevP Apply the UMBRA Implement FRPs Apply regulatory trade-offs: use surrogate endpoints for expedited market authorisation Develop and implement ICT system Formalise the QMS	Monitoring and Evaluating Identify the milestones in the regulatory review process Formalise the target timelines for the review process Record and measure the timelines for each of the milestones Monitor the timelines to ensure that target timelines are met Embed the target timelines in performance contracts Prioritise the implementation of the EDMS to ensure the accurate tracking of applications and recording of the timelines achieved	MA04.06: The establishment of timelines for the assessment of applications and an internal tracking system are required to follow the targeted timeframes
					MA06: The use of a mechanism to monitor regulatory performance and output is required
					MA06.02: The establishment and implementation of performance indicators for registration and/or market authorisation activities is required
					RS10.01: The monitoring, supervision and review of the performance of the NRA is required using key performance indicators
Study 417	Compare the registration process and the regulatory review model of the MCC to that of 4 other similar-sized regulatory authorities	A questionnaire was used to describe the structure, the registration process, good review and decision-making practices of the MCC Similar questionnaires were also completed and validated by Australia’s TGA, Canada’s Health Canada, Singapore’s HSA and Switzerland’s Swissmedic	Define timelines and measure milestones in review process and overall approval time Formally implementing GRevP Apply UMBRA Implement FRPs and apply a risk-based approach to regulatory review process Establish committee structures within the NRA for ad hoc consultation Enhance transparency and communication through development and publication of public assessment report (ZAPAR)	Apply a Risk-Based Approach to Review Formalise FRPs in order to conserve limited resources, avoid duplication of regulatory effort and shorten timelines for medicine registration Consider alternatives to the full review process, such as the abridged review and verification review Rely on or recognise reference agencies’ assessment reports Rely on or recognise the regulatory decisions of reference agencies Strengthen collaborations and initiatives for joint reviews/work-sharing	RS03.04: Reliance on the decisions of other mature NRAs through documented policy, procedures and/or mechanisms must be formalised
					RS09.01: NRAs are encouraged to participate in a regional and/or global network in order to promote convergence and harmonisation efforts
Study 518	Review the PARs available in the public domain against the UMBRA BR Template using a case study approach Evaluate the approach initiated by SAHPRA to document and communicate the BR decision	PARs for 3 NASs published by NRAs in Australia, Europe, Canada, and the United States were compared with the validated UMBRA BR Template to evaluate the BR decision documentation A focus group discussed the use of PARs as potential knowledge management tools for stakeholder understanding of regulatory decision-making The SAHPRA approach to document and communicate the BR decisions was evaluated	Perform BR assessment in a structured, systematic documented manner Preparation and publication of a ZAPAR to communicate the BR decision Use UMBRA BR Template for BR assessment and as an outline for the public assessment report (ZAPAR)	Transparency and Communication Enhance stakeholder relationships through improved communication and transparency Publish updated lists of SAHPRA licence holders and medicine registrations Facilitate online submission and tracking of applications Publish SAHPRA’s summary basis of decision in the form of the public assessment report (ZAPAR)	MA05: NRAs must ensure that mechanisms exist to promote transparency, accountability and communication
					MA05.01: NRAs are required to ensure the availability of a website or other official publication that is regularly updated
					MA05.02: NRAs are required to publish an updated list of all medicines granted market authorisation
					RS09.04: NRAs are required to publish information on marketed medical products, authorised companies and licensed facilities
					MA05.03: NRAs are required to publish the summary technical evaluation reports for approved applications of marketing authorisation in the public domain
					RS09.03: NRAs are required to publish the NRA decisions related to regulatory activities in the public domain
Study619	Identify criteria and current practices for implementing an abridged review process and understanding barriers and enablers in utilising reliance models	A questionnaire was completed by 6 NRAs to determine criteria and current practices for implementing an abridged review process Two focus group discussions were conducted on the practical implementation of an abridged review process based on GRelP	Formalising the implementation of GRelP; Place reliance on trusted NRAs Verify sameness of NAS applications submitted to SAHPRA Limit the scope of the abridged review to a: Detailed review of clinical data Review of the quality data and non-clinical data only in the event of query; and Selective review of human pharmacology data	Training and Education Training programs should be formalised Priority should be placed on the professional development of internal and external assessors Ongoing skills development may be maintained through the initiation of mentorship programmes The development of additional capacity will contribute towards enhanced regulatory performance and shortened timelines for regulatory review	MA03.01: Sufficient competent staff (education training skills and experience) should be assigned to perform marketing authorisation
					MA03.03: The development, implementation and annual updating of the training plan is required
					MA03.04: Performing and maintaining records of staff training activities is required
					RS05.14: The establishment of a mechanism to evaluate and demonstrate the effectiveness of training activities is required

Abbreviations: WHO GBT, World Health Organization Global Benchmarking Tool; BR, Benefit-Risk; FRPs, facilitated regulatory pathways; GRPs, good regulatory practices; GRelPs, good reliance practices; GRevPs, good review practices; SOPs, standard operating procedures; HSA, health science authority; ICT, information and communications technology; MCC, Medicines Control Council; NASs, new active substances; NRA, national regulatory authority; PARs, public assessment reports; QMS, quality management system; SAHPRA, South African Health Product Regulatory Authority; TGA, therapeutic goods administration; UMBRA, Universal Model for Benefit Risk Assessment; ZAPAR, South African Public Assessment Report; ODMPs, quality decision-making practices.