There is more awareness of the South African Health Products Regulatory Authority’s (Sahpra) status as the national regulatory institution, but the understanding of its exact role and importance is blurry, given the expansive scope of products for which the institution is responsible for regulating, and the broad array of activities with which it is tasked, writes Catherine Tomlinson in Spotlight.
Professor Helen Rees, chairperson of Sahpra’s board, said. “Whenever I am asked about the importance of a health products regulatory authority, I ask people if they trust the medicines they buy from a pharmacy or the antibiotic they give to their sick child,” she said. “If they answer yes, then the important role of (Saphra) is quickly understood.”
Ensuring that the medicines used in South Africa are safe and effective is not simple, involving numerous intersecting steps and processes.
To fulfil its mandate for medicines regulation, Sahpra must review safety, efficacy and quality data for new and generic medicines before their market introduction to determine whether they are safe and for what conditions. It must determine whether the facilities in which medicines are manufactured and handled are up to scratch and can consistently produce safe medicines meeting quality standards. Sahpra must also decide whether a medicine should be available over the counter, or require a prescription.
Once a medicine is on the market, Sahpra must facilitate/monitor reporting of adverse events. It must also prevent the import and use of unauthorised medicines through, for example, working with SAPS to seize/destroy unauthorised products.
Sahpra’s mandate is even more complex when considering medicines are only one of the many types of products the institution is responsible for regulating. The body also oversees the safety and efficacy of biological products (including vaccines), medical devices (from implants to diagnostics to face masks), cannabis grown and sold for medical use, complementary medicines, and radiation-emitting devices.
Sahpra was established in February 2018 to replace the Medicines Control Council (MCC), in operation since 1967. Since then, it has made impressive progress in fulfilling its mandate in several areas, though it continues to face challenges in others.
WHO recognition
A highlight for Sahpra in 2022 was the achievement of a maturity level 3 ranking for vaccines regulation from the World Health Organisation (WHO). The WHO uses a ranking system ranging from one (the lowest) to four (the highest) to rank the maturity and effectiveness of health products regulatory organisations in meeting their mandates to ensure health products are safe and effective. Last October, Sahpra received WHO maturity level 3 (ML3) ranking for vaccine regulation and maturity level 4 (ML4) status for vaccine lot release.
Only five health product regulatory authorities on this continent have received a maturity level 3 designation from the WHO. SA and Egypt have received this designation for vaccines regulation, while Ghana, Tanzania and Nigeria have achieved this status for medicine regulation.
And only South Africa has received a maturity level 4 ranking for lot release, which involves evaluating batches of vaccines before they are released for use in the country. All batches of vaccines used in South Africa must be evaluated at the national control laboratory in Bloemfontein before use.
“Considering what this means at global level, we are among the best (at vaccine regulation) across the world,” said SAHPRA CEO Boitumelo Semete-Makokotlela. “Any vaccines manufactured here that would have a SAHPRA authorisation (and are) released by our control lab, can therefore stand scrutiny when considered for the quality, safety and efficacy, and can be made available world.”
Clearing the inherited backlog
Another important development announced earlier at the end of 2022 was the clearance of the regulatory backlog inherited from the MCC. When Sahpra took over from the MCC it inherited around 16 000 regulatory applications dating back to 1992.
Sahpra raised funding for a dedicated budget and staff to clear the backlog, the project being launched in August 2019, and on 2 December 2022, the backlog had been fully cleared.
Reducing decision times
Sahpra has introduced new strategies and approaches both to clear the backlog of applications inherited from the MCC and to speed decision-making on new applications, including introducing “reliance pathways” allowing it to use evaluatory materials and decisions from other regulatory authorities in its decision-making.
It has also enabled rolling reviews, allowing it to review data as they become available (e.g. for Covid-19 vaccines) and piloted engagement meetings with applicants before reviewing applications to reduce the need for back and forth during the application process.
Processing new applications
Sahpra told Spotlight that in its first four years of operations (February 2018 to February 2022), it received 173 applications for registration of new chemical entities (NCEs), 79 applications for registration of new biological entities (NBEs), and 2 428 applications for registration of generic products. (Note: Sahpra clarified that these numbers are similar to, though not exactly the same as, figures reported for the 2021/22 financial year in its most recent annual report, as the figures reported in a financial year include applications received in the reporting year, as well as pending applications from previous financial years).
A total of 55% (95) of the 173 applications for registration of NCEs have been registered, added Sahpra.
Only one of the 173 regulatory applications received for NCEs since February 2018 have been pending a regulatory decision for longer than 590 working days – Sahpra’s targeted decision-making time for NCE registration applications.
Of the 79 applications for registration of NBEs (including vaccines) received, 59% (47) have been registered. Turnaround time for regulatory applications for COVID-19 vaccines has been impressive.
“Sahpra reduced the time taken to register COVID-19 vaccines to less than three months, where the required standard of data is available,” it said.
Of the 2 428 applications received for registration of generic products, 25% (608) have been registered. 51% (1 236) of the applications for registration of generic products received since February 2018 have been pending a regulatory decision for longer than 250 working days – Sahpra’s targeted turnaround time for registration of generic products.
These data show that while the new regulator has been able to keep pace with applications received for NCEs, a concerning new backlog of generic medicine applications has already developed. This backlog may delay market entry for certain generic medicines, thereby contributing to reduced competition and higher prices.
Funding shortfalls
Funding shortages are a key challenge to fulfilling its mandate. Semete-Makokotlela told Parliament in October 2022 that “while we were able to achieve what we have, it’s been financially challenging … our country has a tight fiscus and … it is important the regulator is adequately capacitated.”
Its allocation from Treasury has declined, funding from Treasury falling from R183m in the 2019/20 financial year to R146m in 2021/22. Sahpra has been able to offset some of these losses by generating more fee income. Fee-generated income rose from R54m in the 2019/20 financial year to R181m in 2021/22.
In October, Sahpra’s CFO Regardt Gouws said the 2021/22 financial year marked the first year Sahpra’s income raised through fees exceeded government grants. In 2022, Sahpra also received its first unqualified audit – reflecting the regulator’s strengthened financial management and reporting systems.
However, adequate government financing remains critical to ensuring it can carry out its mandate without undue influence from fee-paying companies.
Staff shortages
Funding shortfalls have contributed to staffing shortages and more staff are needed for digitisation, quality management, regulatory inspections and pharmacovigilance.
“At the MHRA (Medical and Healthcare Products Regulatory Agency) in the UK, the size of the team they have in the area of pharmacovigilance is about 60 individuals. Sahpra has only have five people … So, we are severely understaffed,” said Semete-Makokotlela.
Sahpra’s 2021/22 annual report reflected that only 265 out of 375 positions are filled: 95 positions remain unfunded and filling these requires an additional R67m in annual funding.
Sahpra told Spotlight that progress has been made since the October presentation to Parliament and that only 25 positions now remain unfunded.
Funding has been secured to fill previously unfunded positions through fee-generated income, from the Global Fund (via the Department of Health), and through securing approval from National Treasury to run on a budget deficit based on prior accumulated revenue surpluses.
Funding was also secured from Germany’s development agency (GiZ GmBH) and the UK Department of International Trade to support its planned digitisation efforts and additional funding proposals for these efforts were going out.
Withstanding political pressure
Critical for any health products regulator is maintaining its independence and ensuring decisions are evidence- and science-based, made purely in the public interest. In its first few years, Sahpra’s leadership team had a crash course in handling political pressure after intense pressure, protests, and even legal challenges regarding the regulation of health products for Covid-19, and the introduction of regulatory processes for complementary medicines.
However, it is faring well in ensuring its decision-making processes remain independent and are not influenced by outside interests or pressure. Where needed, it has defended its decisions in court.
What next?
Sahpra has also made significant strides toward strengthening its capacity and fulfilling its mandate over the past year. In 2022, Sahpra received its first unqualified audit, cleared the backlog of regulatory applications inherited from the MCC, and received strong validation of its effectiveness in regulating vaccines from the WHO.
Further, over the past few years, it has been agile in responding to Covid-19 – developing new processes to regulate relevant products and reducing decision-making times.
Yet, much remains to be done to address areas for which regulatory systems must still be developed and strengthened, including complementary products and medical devices and tackling its organisational weaknesses (i.e., lacking digital systems and skills).
It has also become more transparent and improved its communications, most notably with a searchable database of registered products, but here too there remains some way to go, especially on the reasoning and evidence behind regulatory decisions.
Sahpra has highlighted plans to further strengthen the organisation’s capacity over the next year by focusing on digitisation and recruiting more staff. A process is also under way to review the Medicines and Related Substances Act to assess whether legislative reform is needed to address ambiguities and align the Act with the current context and needs.
Spotlight article – Analysis: How well did SAHPRA do in 2022?(Creative Commons Licence)
See more from MedicalBrief archives:
SAHPRA clears backlog of new drugs registrations, but ‘still too slow’
SAHPRA’s Helen Rees: an appetite for justice
Seal of approval for SAHPRA systems from WHO
SAHPRA boss Semete-Makokotlela a leader with ‘unparalleled focus’