THE BEST MEDICINE
SA’s drug regulator is ‘a pillar of public health’: What is it and how does it work?
Despite needing more resources and government support, the South African Health Products Regulatory Authority refuses to renege on its duty to stick to the scientific evidence and keep medicine standards sky high. Two of its top brass explain how the regulator works, how it maintains independence and where it is at in evaluating Covid-19 vaccines, ivermectin and cannabis products.
The South African Health Products Regulatory Authority (SAHPRA) monitors and evaluates the full “life cycle” of every authorised health product in South Africa in order to keep the public safe, agreed the regulator’s CEO, Dr Boitumelo Semete-Makokotlela, and the chairperson of its board, Professor Helen Rees.
Scientific evidence, and not the interests of competing stakeholders, is what matters most in their decisions.
They were discussing what types of decisions the regulator can make and on what grounds during a recent Daily Maverick webinar facilitated by Maverick Citizen editor Mark Heywood.
Semete-Makokotlela holds a PhD in Biochemistry as well as a MSc in Management Finance and Investment. She became CEO in January 2020 – just before the start of the Covid-19 pandemic, pointed out Heywood.
Rees is Executive Director of the University of the Witwatersrand’s Reproductive Health and HIV Institute.
SAHPRA is the result of the amalgamation of the Medicine Controls Council and the Directorate of Radiation Control in 2017. Its scope expanded to include regulation of complementary medicine, explained Semete-Makokotlela. It is governed by the Medicines and Related Substance Act (No 101 of 1965 as amended) as well as the Hazardous Substances Act (No 15 of 1973).
It is an independent entity which reports to the national health minister through its board.
SAHPRA has regulatory oversight of every clinical trial in the country, such as those evaluating medicines or medical devices. This goes for human and animal health products, said Semete-Makokotlela.
It begins monitoring in the first phase of the trial when safety is assessed. It requires sufficient safety data from the research and development team and monitors the trial until its conclusion.
It assesses whether or not the product can be registered only after it receives data which meet the regulatory requirements. Key considerations are the safety, quality and efficacy of the product, she explained.
After the product is approved, the regulator inspects the quality standards of the entire value chain – from clinical trials to distribution.
The regulator continues to monitor the product once it’s available in the market. It has oversight of general medicines, which are for purchase over the counter or with a prescription, complementary medicines and medical devices.
The authority was responsible for the oversight of the molecular tests, serology tests and ventilators which were being developed in South Africa as the Covid-19 pandemic began. “We had to make sure these are quality products. We had to review every single product,” said Semete-Makokotlela.
“South Africa remains very fortunate. If you go into a pharmacy and see all the medicine on the shelves which are prescribed, you can be pretty sure that those are safe medicines”, said Rees. The packaging will be truthful about what the medicine contains and how it will affect you.
“The reliance and the confidence that the public can have in health products across the board is really profound and it’s one of the most important pillars of our health system. Without medicine and access, much of what we want to do as clinicians won’t happen,” she added.
The regulator takes into account the health concerns of the moment, Rees said. It may be more urgent to evaluate and approve a brand-new oncology medicine than to register the 20th generic of another medicine. During the pandemic it was necessary to allow emergency authorisation because things could not be “business as usual”.
Rees acknowledged that health regulators used to be “faceless beasts” who were autocratic and took decisions behind closed doors – but no more. “The mood is changing.”
Globally, regulators are trying to have a “bigger dialogue” with communities to hear what people are saying about what works and what is important. In addition, regulators are starting to exchange information about the medicines they monitor to quicken their processes.
The matter of independence is “incredibly important” for the regulator, assured Rees.
This was because it existed in an environment of competing interests of the manufacturer, the public, professional groups or politicians.
It has to have the independence to rely solely on scientific evidence when it makes decisions, she said. If anyone was to ask the top brass at SAHPRA who they served, they would say “the public”.
The regulator has put a big emphasis on conflict of interest, Rees added. As a result, all the board members and staff signed an annual declaration and were asked before any meeting if there is a potential conflict of interest.
Heywood remarked that an often-heard criticism of SAHPRA is that it takes too long to authorise health products.
The regulator is committed to working on speeding up its processes of authorising medicines, responded Semete-Makokotlela. “We may not get it all correct now, but we’re definitely heading in the right direction.”
It does rely on the work of other regulators, such as those in the US – but has the independence and autonomy to make its own decisions, she explained.
SAHPRA has about 290 staff and about 100 external experts who assist with specific reviews. “The intention is, with time, to build a lot of this capability internally,” she said.
This would fast-track their work. There was a need for the government to invest in the regulator to ensure it was fully equipped to do its work. However, it did use its own income from fees to build the institution.
SAPHRA is a “much, much better” regulator than the Medicines Control Council (MCC) “but we’re not there yet”, added Rees. “We need a bigger budget and we need more expert staff.”
When the MCC became SAHPRA, there were 16,000 products in the backlog because of the MCC’s outdated reviewing procedure. These procedures had to be fundamentally “re-engineered” to solve the problem, said Rees.
Section 21 is a section of the Medicines and Related Substance Act 101 of 1965 which allows the regulator to authorise health products that are not yet registered in the country and make them available in specific quantities to specific patients. Follow-up reporting is required in this case, explained Semete-Makokotlela.
SAHPRA is tightly controlled by legislation and regulation, said Rees. For instance, the act does not provide for the regulator to look at the price of products.
Nevertheless, it does have a pricing committee which considers the question of affordability of products, said Semete-Makokotlela.
Rees explained that legislation and regulation are not static and neither is public health. Affordability needs to be discussed, manufacturing capabilities need to be expanded and the registration of generics needs to be fast-tracked to create more competition and lower prices, she said.
The act was amended in 2017 and SAHPRA has started internal discussions about further amendments, added Semete-Makokotlela.
SAHPRA has been instrumental in the oversight of Covid-19 vaccines available in South Africa. Vaccines are biological products and require their own unique assessment process. The process begins by analysing data from the laboratory, animal studies and early to late-stage clinical trials, Rees explained.
Safety is “critical” in each data set. Vaccines do have minor side-effects after administration, but what SAHPRA looks at are unusual, atypical and unusual events which are only seen once the vaccine has been widely rolled out, she added.
When these events occurred, the regulator had to determine whether they had been caused by the vaccine itself – if they were causal, it needed to determine if the benefit of that vaccine outweighed any potential risk.
For instance, the risk of thrombosis from Covid-19 is 100 times higher than the risk from the AstraZeneca and Johnson & Johnson Covid-19 vaccines.
SAHPRA has authorised the Covid-19 vaccines developed by Pfizer, Johnson & Johnson and AstraZeneca, Semete-Makokotlela confirmed. The regulator was at an “advanced stage” of evaluating the Sinovac and Sputnik V vaccines. It had been engaged in “pre-submission meetings” with “many more” applicants.
After authorisation, the applicant has to supply the regulator with safety data once the vaccine is administered. The regulator also relies on the public to provide feedback through the Med Safety app on any side-effects. Teams with a wealth of experience in monitoring vaccines will analyse the data.
Beyond vaccines, SAHPRA has also evaluated medicines that could potentially be used to treat Covid-19, including ivermectin.
Rees said people looked at ivermectin in the laboratory setting and thought it might have some benefit in treating Covid-19. Some clinical trials were done to explore this, but they varied in design and many were very small. They were not of strong quality, so the results were not of a high quality.
SAHPRA, the National Essential Medicines List, the Ministerial Advisory Committee on Covid-19 and the Infectious Disease Society of South Africa combined the data independently of one another to determine whether or not the product works. The World Health Organization also did this. They all found that there was insufficient quality data to say that ivermectin works in the treatment of Covid-19.
There are ongoing studies and SAHPRA is “looking and waiting” for the data, Rees said.
Ivermectin was authorised for veterinarian use, but this does not mean it is safe for humans to take: This medicine is produced in a different way and concentration, she explained. Nevertheless, people took it despite the risk of overdose and side-effects. In addition, illegal imports of the drug contained impurities.
As a result, SAHPRA decided that a fair middle ground was to allow healthcare professionals to administer the medicine under strict conditions and report on it to SAHPRA.
Beyond Covid-19, much attention has been paid to SAHPRA’s evaluation and authorisation of the medical use of cannabis, said Heywood.
Semete-Makokotlela said the majority of applications to do with cannabis are for the export of bulk raw cannabis as well as licensing for cultivation. “We are yet to receive an application with clinical data for its use against a certain condition. We know in other jurisdictions it has been authorised and we’re very much open to that. We will apply the same principles of safety, quality and efficacy.”
Rees added: “Listening to what people are saying to us about ivermectin or cannabis is important, but sometimes too much is asked of the regulator. Can the regulator solve the national cannabis issues? The regulator has a very specific role in the value chain. We are trying to listen to be as flexible in that role as possible. I know people don’t necessarily hear or see that, but truly we are.”
Semete-Makokotlela said: “Scientific information is the only thing that influences us.”
The regulator was stringent in its work so that people in South Africa never had to question whether a product on a pharmacy shelf was safe and would do what it promised to do.
“We may not always agree on the decisions we make, but at the core of it is to ensure the lives of the people are safe.” DM/MC
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