3.2.1 Outcomes, Outputs, Output Indicators, Targets and Actual Achievements

Backlog Clearance Programme

In 2018, SAHPRA inherited a backlog of over 16 000 medicine applications (new registrations and variations, i.e., changes to registered products) from its predecessor, the Medicines Control Council. To address this backlog, SAHPRA established a Backlog Clearance Programme, with dedicated staff, to clear all these applications. The Programme was tasked with optimising processes and implementing efficiencies, using totally re-engineered approaches for medicines assessment and registration. This included the introduction of reliance procedures that allowed SAHPRA to exchange information with recognised regional and international regulatory authorities. A further mandate was to establish the feasibility of risk-based assessment of certain aspects of generic applications. SAHPRA receives over 90% generic medicine (multi-source medicine) applications.

To this end, SAHPRA implemented various review approaches to eradicate the backlog of orthodox product registrations (with the exclusion of biological medicines). The Backlog Clearance Programme utilised the following review pathways:

• Full review – conducting complete scientific review for safety, quality, efficacy and Good Manufacturing Practice.
• Reliance pathways, such as:

o Abridged review – assessing specific, pre-agreed areas of critical importance to SAHPRA’s mandate to ensure safety of the South African public.

o Verified review – validating that application conforms to reference authorisation and provide required information.

o Risk-based assessment of critical quality attributes for applicable generic applications.

Overall, as at 31 March 2022, the backlog applications were cleared by 94%. This figure comprises the 15 168 applications finalised over the 16 170 applications included via the industry survey in the Backlog Clearance Programme. This figure also takes into account clearance initiatives prior to the Go-Live, such as applicant opt-outs, Starburst, certification variations, as well as non-resubmissions.

On 1 August 2019, the Backlog Clearance Project’s official Go-Live was launched. Since the launch of the Go-Live, SAHPRA cleared 86% of the backlog applications. This figure comprises the 5 954 applications finalised over the 6 957 applications received. Furthermore, this figure considers clearance of new registration and variation applications actually submitted after Go-Live and does not include the number of non-resubmissions by applicants after Go-Live. The resubmitted applications were processed through various mechanisms that included official withdrawals by applicants, non-accepting/rejecting non-compliant applications and registering/approving compliant applications.

In an effort to increase the finalisation of new registration applications, the Backlog Clearance Programme initiated a risk-based assessment pilot study that focused on the assessment of critical quality attributes of generic applications. The risk-based assessment study has shown that the quality aspects of approximately 85% of applications were evaluated and finalised within three months. In a measure to reach the project finalisation date of 31 December 2022, the second phase of this pilot study will be rolled-out during the 2022/23 financial year.

Health Products Authorisation

The 246 New Chemical Entity (NCE) applications received included applications carried over from the previous financial year and applications received up until March 2022. Out of the 246 NCE applications received, 44 (18%) NCEs were finalised. Out of the 44 NCEs finalised, 43 (98%) were finalised within 590 working days from date of receipt and all 44 (100%) were finalised within 590 working days from the date of completion of technical screening.

The 2 075 generic applications received included applications carried over from the previous financial year and applications received up until March 2022. Out of the 2 075 generic applications received, 184 (9%) were finalised. Out of the 184 generics finalised, 68 (37%) were finalised within 250 working days from date of receipt and 148 (80%) generics were finalised within 250 working days from the date of completion of technical screening. The registrations encompassed the therapeutic areas such as antihistamine, anti-acid, anti-infectives, oncology, antiviral and anti-tuberculosis. Generic medicine applications from April 2020 onwards are already in a backlog. Various strategies are being implemented to reduce and clear this backlog. These strategies include the implementation of various forms of reliance that involve making use of assessment reports from recognised regulatory authorities and SAHPRA, which contributed towards reducing the review timelines of applications.

Quality Management Systems

SAHPRA continued its effort in implementing an effective QMS. The implementation of the QMS is an important deliverable of the regulatory system required for a mature regulatory agency as advocated by the WHO. Some of the key initiatives implemented during the financial year include the implementation of document management system and the appointment of QMS representatives.

In preparation for ISO 9001 certification, SAHPRA conducted its first annual QMS internal audit and the recommendations emanating from the audit are being addressed. Furthermore, SAHPRA held its first QMS review. The review allowed SAHPRA to reflect on its performance in all the QMS initiatives. This review will be held annually to determine and evaluate management system performance, the need for change and improvement as well as the suitability of business policies and objectives.

A key focus for SAHPRA was to work towards obtaining a Maturity Level 3 rating for regulatory systems based on the WHO Global Benchmarking Tool. The benchmarking assessment was conducted and an Institutional Development Plan was developed for SAHPRA to address areas of weaknesses identified. The final benchmarking assessment will be concluded during the 2022/23 financial year, wherein the maturity level rating will be awarded.

3.2.2 Linking Performance with Budgets

3.2.3 Strategy to overcome Areas of Underperformance

To improve the number of backlog applications for medicine registrations cleared, a risk-based assessment pilot study was initiated in September 2021. This has resulted in shortened review and applicant response timeframes. The implementation of the second phase is scheduled during the 2022/23 financial year. This will further assist in mitigating the long extension requests from applicants to respond to quality and bioequivalence queries. The Backlog Clearance Programme will, moreover, continue to assess extensions granted to applicants, taking cognisance of the nature of the queries as well as external impediments experienced by individual applicants.

In preparation for the final WHO benchmarking assessment to determine SAHPRA’s maturity level, the implementation of recommendations from the Institutional Development Plan are being accelerated.

3.2.4 Reporting on the Institutional Response to the COVID-19 Pandemic

3.3 Programme 3: Inspectorate and Regulatory Compliance

Purpose: To ensure public access to safe health products (include disclaimer) through inspections and regulatory compliance. The focus of this programme includes assessment of site compliance, with good regulatory and vigilance practices, including the following:

• Good Manufacturing Practice
• Good Clinical Practice
• Good Warehouse Practice
• Good Distribution Practice
• Good Laboratory Practice
• Good Vigilance Practice

Sub-programmes

Outcomes:

• High levels of organisational operational efficiency and effectiveness in the regulatory function maintained (7).

3.3.1 Outcomes, Outputs, Output Indicators, Targets and Actual Achievements

Licensing

During the 2021/22 financial year, 31 Good Warehouse Practice and Good Manufacturing Practice related licences were finalised for first time applicants. There was a decrease in the issuing of licences for manufacturers of alcohol-based hand-rubs who were prioritised in response to COVID-19 in the previous financial year. The processing of 28 licence amendments and 33 licence renewals were also conducted.

Inspectorate

Support was provided to the Business-As-Usual and backlog registration streams in terms of evaluation and/or inspection requirements for Good Manufacturing Practice to support the registration of products. To reduce the backlog of Business-As-Usual registrations, additional resources were allocated to assist in increasing dossier evaluations for Good Manufacturing Practice clearance. In total, 168 GxP inspections were conducted.

Regulatory Compliance

The medicinal cannabis market continues to expand, requiring engagement at a national level. SAHPRA remains an integral stakeholder in the Cannabis Master Plan, whilst maintaining its current role as an enabler of the increasing cultivation market for medical cannabis export. During the financial year, 74 cannabis cultivation inspections were completed.

During the 65th Session of the Commission on Narcotic Drugs held in March 2022, SAHPRA was invited by the International Narcotics Control Board (INCB) to co-sponsor at their parallel event on International Standards for Reporting Cannabis and Cannabis-Related Substances for Medical Purposes by sharing its experience with INCB. The speakers at the session included the President of INCB and other speakers from the United Nations Office on Drugs and Crime, Japan, United States of America, Germany, United Kingdom and New Zealand. In addition, during the session, SAHPRA also participated at the RSA Vienna Mission led parallel event on cannabis.

3.3.2 Linking Performance with Budgets

3.3.3 Strategy to overcome Areas of Underperformance

To improve the finalisation of new Good Manufacturing and Good Warehouse Practice related licenses, internal mechanisms have been initiated and prioritised to ensure improved communication and cooperation for inspections of these new licences.

3.3.4 Reporting on the Institutional Response to the COVID-19 Pandemic

The guideline for conducting inspections during the COVID-19 pandemic remained operational whilst the country remained under lockdown restrictions. The guidelines assisted the inspectors to assess and manage the risk of exposure in interactions during inspections. International inspections commenced through virtual inspection, which required a readiness test with site prior to commencing the inspection.

The issuing of physical licences continued, and this was managed by ensuring that appointments were made for applicants to collect their licences.

3.4 Programme 4: Clinical and Pharmaceutical Evaluation

Purpose: To evaluate the safety, quality and therapeutic efficacy of medicines and register them for use as per delegated authority in terms of relevant legislation as listed in the legal mandate of part 1a of the strategic plan.

Sub-programmes

Outcomes:

• High levels of organisational operational efficiency and effectiveness in the regulatory function maintained (7).

3.4.1 Outcomes, Outputs, Output Indicators, Targets and Actual Achievements

Category A (Human) Medicines

As part of enhancing the country’s COVID-19 regulatory response, SAHPRA continued to provide access to Ivermectin for the treatment of COVID-19 through the controlled compassionate use programme for approved unregistered Ivermectin products. The majority of unregistered medicines that treat COVID-19 infections were approved within 24 working hours. Out of 9 385 applications finalised within 24 working hours, the following categories were reported:

• Named patients: 5 207 (55%)
• Bulk stock: 4 140 (44%)
• Reauthorisations – named patients: 23 (0.25%)
• Reauthorisations – bulk stock: 15 (0.16%)

For the 2021/22 financial year, the following top 10 Section 21 product requests were approved or rejected as indicated in the table below:

Human Clinical Trials

To promote the conduct of clinical trials related to the ongoing COVID-19 pandemic, SAHPRA’s clinical trial protocol submission guidelines were amended and implemented. The review of COVID-19 clinical trials was expedited to enhance the country’s COVID-19 emergency response and the approval turn-around time was between 7 to 10 working days.

Pharmacovigilance

The Med Safety App was launched in April 2021 to facilitate the reporting of AEFIs for vaccines and to act as a platform for collecting adverse drug reactions for other health products going forward. During the course of the financial year, there was an increase in the utilisation of the Med Safety App. To further enhance the safety monitoring of registered medicines, medicines’ safety reporting guidelines were published for implementation. Furthermore, CoviVig, a dedicated pharmacovigilance project to closely monitor treatment outcomes of medicines used off-label for COVID-19 is in place to further obtain safety and efficacy data on repurposed registered medicines and novel unregistered medicines used to treat COVID-19 and its complications.

To promote vigilance awareness within the country, for both healthcare professionals and the public, the National Vigilance Framework in South Africa was developed and will be implemented during the 2022/23 financial year.

3.4.2 Linking Performance with Budgets

3.4.3 Strategy to overcome Areas of Underperformance

To improve the turnaround time for the authorisation of Section 21 applications, the ICT system utilised is being improved to accurately calculate the processing timelines from when a complete application is submitted and finalised.

Additional human resources will be obtained to deal with health product safety signals. Furthermore, to reduce the reliance on external experts, a training programme for internal employees of SAHPRA has commenced.

3.4.4 Reporting on the Institutional Response to the COVID-19 Pandemic

In addition to the above-mentioned initiatives under 3.4.1, SAHPRA authorised COVID-19 vaccines under Section 21 as the emergency use authorisation mechanism for Covishield, Pfizer (Cominarty®), COVID-19 Vaccine Janssen® and SinoVac CoronaVac vaccines. Section 21 Sputnik V Lamar application was rejected, and approval was granted for Pfizer (Cominarty®) third dose for booster (homologous) and COVID-19 Vaccine Janssen® booster (homologous and heterologous).

As South Africans continued to receive immunisations, SAHPRA closely monitored the COVID-19 AEFIs. Although the overall achievement for health product safety signals was low, there was a reasonable turnover for COVID-19 related safety signals where 65% were processed within the target timeline, with a median processing timeline of 21 days.

Collaboration with the Council for Scientific and Industrial Research (CSIR) resulted in the analysis of COVID-19 vaccine safety data, resulting in the weekly publication of the vaccine safety statistics on SAHPRA’s website (https://aefi-reporting.sahpra.org.za/). This has promoted transparency in terms of emerging and known vaccine safety concerns and how SAHPRA in collaboration with NDoH, tracks these safety concerns and utilises the data to further mitigate safety concerns around COVID-19 vaccines.

3.5 Programme 5: Medical Devices and Radiation Control

Purpose: To develop and maintain regulations and guidelines pertaining to the regulatory oversight of medical devices, radionuclides, and listed electronic products.

Sub-programmes

Outcomes:

• High levels of organisational operational efficiency and effectiveness in the regulatory function maintained (7).

3.5.1 Outcomes, Outputs, Output Indicators, Targets and Actual Achievements

Medical Devices and Radiation Control

Standard Operating Procedures (SOPs) were implemented to ensure that there is efficient regulatory management. The streamlining and re-focusing of functions also assisted in ensuring that there are efficient operations.

To improve communication with the industry and process efficiencies, stakeholder engagements were increased with the following engagements held:

• Industry workshop (Licence renewals and conformity assessment bodies). Communication to industry.
• Workshop with the International Atomic Energy Agency (Disused source and transportation of active sources).

The availability of the community service pharmacist for 12 months assisted in improving the performance with regards to the finalisation of medical device applications. The adoption of digital solutions remains imperative to ensure the efficient functioning of the regulation of medical devices. SAHPRA received public comments on the regulations for medical devices and three workshops were held with respondents and members of the Industry Technical Working Group as well as the Medical Device Committee to discuss the areas that received the most comments. The collaboration with industry assisted with understanding the comments from them in addition to offering SAHPRA the opportunity to state its standpoint on certain topics within the regulations.

SAHPRA is working in collaboration with other national regulatory authorities in creating and reviewing various guidance documents using platforms such as the African Medical Device Forum, of which SAHPRA is co-chair. As part of the WHO Global Model Regulatory Framework Working Group for medical devices including in vitro diagnostics, SAHPRA participated in updating the WHO Global Benchmarking Tool and the tool for medical devices. Furthermore, SAHPRA is participating in the WHO Collaborative Registration Procedure. This procedure is for WHO-prequalified products, and it accelerates registration through improved information sharing between the WHO Prequalification Process of Medicines Programme, national regulatory authorities, and the WHO National Regulatory Authority Strengthening Programme.

Radiation Control implemented robust business processes that resulted in efficient processing of applications and issuing of licences. The achievements are an indication that the regulatory framework for radionuclides and listed-electronic products licensing has been effective and ensures compliance monitoring of licence and authority holders across the entire country.

SAHPRA continued to engage with the Department of Minerals and Energy and the National Nuclear Regulator on legislative and regulatory matters with the intention to define the co-regulation framework among the stakeholders as well as the revision of respective Acts.

3.5.2 Linking Performance with Budgets

3.5.3 Strategy to overcome Areas of Underperformance

With regards to the medical device registration regulations, additional capacity will be sourced to ensure the speedy finalisation of the regulations. Policies, guidelines, and SOPs to manage the internal and external engagements will be developed. The technical expert committee will assist with the implementation of the policies, regulations, and guidelines.

It is anticipated that the co-regulations between SAHPRA and the National Nuclear Regulator will be completed during the 2022/23 financial year. Feedback on progress will be requested from the working group on a regular basis.

3.5.4 Reporting on the Institutional Response to the COVID-19 Pandemic

Engagements were held with multidisciplinary stakeholders such as the National Institute of Communicable Diseases of South Africa, the National Health Laboratory Services, WHO, the Medicines and Healthcare Products Regulatory Agency, HIV research organisation – Ezintsha and the Clinton Health Access Initiative to approve the use of self-test/home-based SARS COVID-19 test kits.

4. REVENUE COLLECTION

Better than anticipated revenue collection occurred due to new medicine registration percentage completion reached for certain applications.

Revenue recognition will improve as SAHPRA fills funded vacancies in the 2022/23 financial year.

5. CAPITAL INVESTMENT

SAHPRA is a Public Finance Management Act (PFMA, 1999, as amended) Schedule 3A public entity under NDoH. SAHPRA manages its assets in line with its Asset Management Policy and has not embarked on any infrastructure projects and did not close down or downgrade any facilities during the year.

No maintenance activities were undertaken during the year as the entity did not own significant infrastructure or moveable assets that required continuous maintenance. SAHPRA has current office accommodation lease arrangements for its head and regional offices and the rental expenses associated with the new operating lease agreement was appropriately disclosed in the notes of annual financial statements.

A significant portion of SAHPRA’s assets for the 2021/22 financial year comprises newly-acquired assets. These acquisitions amounted to R5.6 million on 31 March 2022. The new acquisitions include other fixed assets (R295 243), computer equipment (R2 857 938), furniture (R63 592), motor vehicles (R971 954) and intangible assets (R1 294 018). The disposals for the year comprised old furniture and computer equipment which were transferred from NDoH and were no longer in use or had been replaced, which were either sold or donated. A significant portion of these assets was fully depreciated.

SAHPRA has an Asset Management Unit within its Finance Department that is responsible for updating the asset register including all asset transactions such as receipts, movements, disposals, useful life assessments and other changes. The unit conducts asset verifications at least twice a year in terms of the approved Asset Management Policy.