Following the emergence of Covid-19 and the regular mention of the South African Health Products Regulatory Authority (Sahpra) in the news – mostly in relation to what health products have or have not been registered for use against Covid – more people are now familiar with Sahpra as a national regulatory institution. 

Yet understanding Sahpra’s precise role and its importance remains tricky, given the expansive scope of products that the institution is responsible for regulating, as well as the broad range of activities that it must carry out to fulfill this role.

Professor Helen Rees, chairperson of Sahpra’s board, has found her own way of trying to explain what the regulator does and why it is important:

“Whenever I am asked to give the elevator speech about the importance of a health products regulatory authority, the easiest pitch is to ask people if they trust the medicines they buy from a pharmacy or the antibiotic they give to their sick child,” says Rees. “If the answers are yes, then the important role of [Sahpra] is quickly understood.”

The processes for ensuring that the medicines used in South Africa are safe and effective are by no means simple. Rather, they involve a complex array of intersecting steps and processes. 

To fulfill its mandate for medicines regulation, which is outlined in the Medicines and Related Substances Act, Sahpra must review safety, efficacy, and quality data for new and generic medicines prior to their market introduction to determine whether they are safe for use in the country and for what conditions. 

The regulator must determine whether the facilities in which medicines are manufactured and handled are up to scratch and are consistently able to produce safe medicines that meet quality standards. 

Sahpra must also decide whether a medicine can be made available over the counter, or if its use requires a prescription. And once a medicine is on the market, Sahpra must facilitate and monitor reporting of adverse events. 

In addition to regulating the use of approved medicines, Sahpra must take steps to prevent the import and use of unauthorised medicines in the country through, for example, working with the police to seize and destroy unauthorised products.

Sahpra’s mandate appears even more dizzying when one considers that medicines are only one of the many types of products that the institution is responsible for regulating. 

In addition to medicines, Sahpra must ensure the safety and efficacy of biological products (including vaccines), medical devices (which range from medical implants to diagnostics to face masks), cannabis grown and sold for medical use, complementary medicines and radiation-emitting devices.

Sahpra’s processes and capacity for regulating different types of health products are at different stages of development, with medical device regulation, for example, being introduced in a phased manner, while the scope of complementary medicines that Sahpra must regulate remains under consideration following a court ruling that an earlier definition of complementary medicines was overly broad.

Sahpra was established in February 2018 to replace the Medicines Control Council (MCC), which had been in operation since 1967. Since then, the still relatively young institution has made impressive progress in fulfilling its mandate in several areas, though it continues to face challenges in others. 

WHO recognition

The most exciting development at Sahpra in 2022 was the achievement of a maturity level 3 ranking for vaccines regulation from the World Health Organization (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 that health products are safe and effective. 

Following an initial 2021 and subsequent 2022 assessment of Sahpra by the WHO, the regulator announced in October 2022 that it had 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 the African continent have received a maturity level 3 designation from the WHO. South Africa and Egypt have received this designation for vaccine regulation, while Ghana, Tanzania and Nigeria have achieved this status for medicine regulation. 

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 prior to their use.

Achievement of these WHO rankings for vaccine regulation and lot release provides strong reassurance that vaccines used in South Africa are appropriately evaluated, safe, and effective. It also provides a boost for the country’s nascent vaccine manufacturing sector. 

“If you consider what this means at a global level, is that we are among the best [at vaccine regulation] across the world,” says Sahpra CEO Boitumelo Semete-Makokotlela. 

“Any vaccines that are manufactured in South Africa, that would have a Sahpra authorisation [and are] released by our control lab, can therefore stand scrutiny when they’re considered for the quality, safety and efficacy. So, these vaccines can be made available across the world.” 

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Clearing the inherited backlog

Another important development at Sahpra, announced earlier this month, 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 developed a plan and raised funding for a dedicated budget and staff to clear the inherited backlog. The backlog clearance project was launched in August 2019 and, on 2 December 2022, Sahpra announced that the backlog had been fully cleared.

Dr Nicholas Crisp, Deputy Director-General for National Health Insurance at the Department of Health, called clearance of the backlog “a milestone for Sahpra”, while Stavros Nicolaou, chairperson of the Pharmaceutical Task Group (PTG), said the PTG “welcomes this development and congratulates the Sahpra board and management in achieving the significant clearing of the registration backlog that has historically hampered the MCC”.

Reducing decision times

Sahpra has explained that the regulator has introduced new strategies and approaches both to clear the backlog of applications inherited from the MCC and to speed up decision-making on new applications made to Sahpra. 

These strategies include introducing “reliance pathways” that allow Sahpra to use evaluatory materials and decisions from other regulatory authorities in its own decision-making processes. 

“We enter into agreements for information sharing [with other regulators] and we cooperate in making regulatory decisions,” explains Kuda Kapfumvuti, senior manager of Health Products Authorisation at Sahpra. He says this allows Sahpra to “rely on prior decisions that have been taken by well-resourced and mature regulators … [and] focus our efforts only on issues that are specific to circumstances in the country”.  

In addition to developing the relevant guidelines and entering agreements to enable Sahpra to draw on the efforts of other regulators, Sahpra has also introduced rolling reviews to allow the regulator to review data as it becomes available (as done for Covid-19 vaccines) and piloted engagement meetings with applicants prior to reviewing applications to reduce the need for back and forth during the application process. 

Sahpra has pinpointed incomplete applications that require back-and-forth engagement with applicants, and delays in receiving unredacted information from other regulators, as key culprits behind delays in regulatory decisions.  

Processing new applications

According to data supplied by Sahpra on request from Spotlight, in its first four years of operations (February 2018 to February 2022), Sahpra 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, according to Sahpra. Only one of the 173 regulatory applications received for NCEs since February 2018 has 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 vaccines has been particularly impressive. 

“Sahpra reduced the time taken to register Covid-19 vaccines to less than three months, where the required standard of data is available,” says Sahpra.

Of the 2,428 applications received for registration of generic products, 25% (608) have been registered. Fifty-one percent (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

The regulator has repeatedly highlighted funding shortages as a key challenge to fulfilling its mandate. 

Semete-Makokotlela told members of Parliament in October 2022 that “while we were able to achieve what we have, it’s been a very challenging period for us from a financial perspective… we are in a country with a very tight fiscus, and, whilst that is the case, I think it is important that the regulator is adequately capacitated”.

Sahpra has seen its allocation from Treasury decline in recent years. Sahpra’s funding from Treasury fell from R183-million in the 2019/20 financial year to R146-million in 2021/22. Sahpra has been able to offset some of these losses by generating more fee income. Fee-generated income rose from R54-million in the 2019/20 financial year to R181-million in 2021/22. 

In October, Sahpra’s CFO, Regardt Gouws, told parliamentarians that the 2021/22 financial year marked the first year that Sahpra’s income raised through fees exceeded government grants. This year, Sahpra also received its first unqualified audit – reflecting the regulator’s strengthened financial management and reporting systems.

While the increase in fee revenue is a step in the right direction to ensuring that the regulator is properly financed, adequate government financing remains critical to ensuring that the regulator can carry out its mandate without undue influence from fee-paying companies.

Staff shortages

Funding shortfalls at the regulator have contributed to staffing shortages. Sahpra told MPs in Parliament in October that 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. At Sahpra, we only have five individuals in this area, and we know that the reports that we receive in terms of numbers are quite comparable. So, we are severely understaffed in this area,” said Semete-Makokotlela.

According to Sahpra’s 2021/22 annual report, only 265 out of 375 positions at Sahpra are filled. Gouws explained to Parliament that 95 positions at Sahpra remain unfunded and that filling these positions would require an additional R67-million in annual funding.

In response to questions from Spotlight, Sahpra indicated that progress has been made since the October presentation to Parliament and that only 25 positions now remain unfunded. 

Sahpra indicated that 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.

Sahpra also told Spotlight that funding has been secured from Germany’s development agency (GiZ GmBH) and the UK Department of International Trade to support its planned digitisation efforts, and that additional funding proposals for these efforts were going out.

Withstanding political pressure

A key function of any health products regulator is to maintain its independence and ensure that its decisions are evidence- and science-based and made purely in the public interest. 

In its first few years, Sahpra’s leadership team has experienced a crash course in how to handle political pressure with the regulator facing intense pressure, protests and even legal challenges related to the regulation of health products for Covid-19, as well as the introduction of regulatory processes for complementary medicines.

Sahpra appears to be faring well in ensuring that its decision-making processes remain independent and are not influenced by outside interests or pressure. Where needed, they have defended their decisions in court. 

Yet, public trust in its regulatory decision-making processes and outcomes may have eroded given the ongoing demand for ivermectin and vaccine reluctance in the country, which is at odds with Covid-19 communications and recommendations from Sahpra.

What is next?

Sahpra has 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, the regulator has been agile in its response to Covid-19 – developing new processes to regulate relevant products and reducing decision-making times. 

Yet, much remains to be done by the regulator to address areas for which regulatory systems must still be developed and strengthened, including complementary products and medical devices and addressing its organisational weaknesses (i.e. lacking digital systems and skills). 

Sahpra has also become more transparent and improved its communications in recent years, 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. 

Sahpra has also said that a process is underway 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. DM

This article was published by Spotlight – health journalism in the public interest.