The plan to revive medicines regulation in South Africa

By Catherine Tomlinson

The South African Health Products Regulatory Authority (SAHPRA) is responsible for the regulation of medicines in South Africa to ensure that medicines marketed in the country are safe, effective and of good quality. In addition, SAHPRA is responsible for the regulation of medical devices, clinical trials and radiation-emitting devices.

SAHPRA replaced South Africa’s previous medicine regulatory authority, the Medicines Control Council (MCC), in February 2018 with the objective of creating an effective regulator that is responsive and publicly accountable and able to make timeous regulatory decisions. However, SAHPRA inherited many historical challenges that plagued the MCC, including slow regulatory decision times, an extensive backlog of pending regulatory applications, and a culture of non-transparency and resistance to public accountability. Since its formation, SAHPRA has developed a range of plans to overcome these challenges, which were outlined in its recent 2019/2020 annual performance plan.

Inherited challenges

At its establishment, SAHPRA inherited a massive backlog of around 16 000 medicine regulatory applications from the MCC. These include applications for “new registrations, variations, duplicates, clones, multiple doses and different dosage forms”.

While 50% of backlogged applications were submitted in the past five years, the backlogged applications date all the way back to 1992 and include applications for high priority public health products, including medicines for HIV, tuberculosis, cancer and diabetes.

The University of Western Cape’s Henry Leng and colleagues have highlighted the adoption of policies to promote generic access as key drivers of the accumulated backlog. In the early 2000s, South Africa adopted policies to fast-track the registration of medicines of high public health priority and to promote generic access. The adoption of these policies led to a large influx of applications for the registration of multiple generic versions of high priority products.

In general, the registration and availability of multiple generic versions of individual medicines is critical to improving medicine access, because competition between generic suppliers drives down prices and improves affordability. Research conducted by the United States’ medicines regulatory authority, the Food and Drug Administration, has shown that it generally takes the introduction of multiple generic products to bring down prices, as the first generic companies to enter the market tend to price their products close to the prices offered by originator companies.

While broad generic competition plays an important role in enabling medicine access, the introduction of policies to promote generic access in South Africa contributed to a regulatory backlog, as they were not coupled with an expansion of capacity at the regulator to process the influx of applications. At the same time, South Africa has struggled with “frivolous” regulatory filings by companies that fail to market their products after receiving registration. In a review of eight priority medicines, Leng et al. found that only 54% of registered generic medicines were actually marketed in the country following registration. Leng et al. suggested that the comparatively low cost of filing for registration in South Africa may encourage filings by companies without serious intentions to market their products, and cautioned that time and resources spent by the regulatory authority on fast-track approval of unmarketed products for which there are already existing alternatives, delays the registration of new products for which there is no equivalent in the country, or existing competition.

Inadequate capacity

SAHPRA has indicated that even without the large inherited backlog, the regulatory authority does not currently have the capacity to timeously process new applications. Evidence shows that while SAHPRA receives an average of 4 700 new applications annually, it is only able to process around 2 550 applications per year. With inadequate capacity to process backlogged and new applications, timelines for registration of medicines in South Africa are typically extremely long.

Research conducted by Keyter et al. demonstrated that the median time for approval of new chemical entities by the MCC was 1 161, 1 678, and 1 422 calendar days in 2015, 2016 and 2017, respectively. Keyter et al. further demonstrated that the median time for approval of fast track applications was 1 218, 921, and 609 calendar days in 2015, 2016 and 2017, respectively – far slower than the regulatory authority’s target for approval of fast-track applications in 250 days.

Slow regulatory decision times in South Africa have serious public health consequences, as they impede access to important and life-saving medicines, as well as cheaper generic versions of medicines, long after they are available on the global market. Recognising this challenge, SAHPRA has set a target to reduce regulatory decision times to 275 working days for new chemical entities and 180 days for registration of generic products. SAHPRA has also set a target to clear the regulatory backlog in two years.

The recently released annual performance plan outlines SAHPRA’s plans to “re-engineer” the regulatory authority to achieve its targets. Its plans include (among other interventions) the strengthening of its human resource capacity, the introduction of a new fees model and the digitisation of key processes.

SAHPRA’s strategy to address the medicine regulatory backlog

SAHPRA has set a target to clear the regulatory backlog in two years – but notes that, at current capacity with no new applications, clearing the backlog will take up to eight years. SAHPRA’s annual performance plan clarifies that the regulator has developed a costed strategy to clear the backlog and has secured ring-fenced funding for the backlog clearance strategy from the government, development partners and donors.

SAHPRA’s strategy to reduce the backlog involves three key elements, including reducing the number of backlogged applications to remove applications that are no longer relevant, prioritising the remaining applications for review according to public health needs and risk, and implementing new regulatory pathways to reduce regulatory decision times.

Given that the regulatory backlog dates back to 1992, it is expected that some applications may no longer be of commercial interest to applicants or of public health relevance. SAHPRA will seek to remove applications that are no longer relevant through requiring applicants who submitted applications in 2013 or earlier to indicate that they would still like their applications to undergo review through a survey template and requiring all applicants to update their applications to meet current requirements. SAHPRA has already begun to implement this and noted in a May 2019 communication that 3 000 applications in the backlog have already been deemed to be withdrawn. Moving forward, SAHPRA has indicated that it will prioritise the remaining backlogged applications for review according to public health risk and need. Public health need will be based on the government’s priority therapeutic areas and unmet medical need, and public health risk will be based on the complexity and type of application and “level of prior scrutiny by recognised regulators”.

In addition to reducing the number of applications and prioritising applications for review according to public health need and risk, SAHPRA has committed to implementing “new evaluation models” to clear the backlog, as well as to facilitate timeous registration of new applications. This strategy will involve the implementation of so-called reliance pathways to facilitate greater collaboration and information sharing with other regulatory authorities.

Reliance pathways provide mechanisms for collaboration across global regulatory agencies, and with the World Health Organisation, by creating pathways that allow regulators to access and use data and reports, and rely on other evaluator decisions, in domestic regulatory decision making. Reliance pathways provide important mechanisms to reduce times to regulatory decision making when capacity challenges impede timeous local decision making. Medicine regulators in both developing and developed countries struggle to manage their workloads and make timeous regulatory decisions due to increasing application volumes, and the need to monitor the compliance of foreign producers to good manufacturing practices (GMP).

Historically, South Africa’s medicine regulators (the MCC and SAHPRA) have not utilised reliance pathways – despite arrangements and collaborations in place with other regulatory bodies to facilitate their use – and selected instead to conduct full scientific reviews of quality, efficacy and safety data for all regulatory applications. However, SAHPRA has now committed to operationalising these pathways to address the backlog and reduce regulatory decision times for new applications. SAHPRA has further indicated that it will formalise processes to facilitate the use of several different reliance pathway models, including full review, abridged review, verified review, recognition and notification – each requiring different levels of local review and evaluation.

Implementation of the “abridged review” model, for example, would allow SAHPRA to rely on regulatory data and evaluations from other agencies (such as the European Medicines Agency), while requiring local review and evaluation of domestic contextual issues – such as the interaction of the medicine under review with HIV treatment.

Building SAHPRA’s human capacity

A further challenge faced at SAHPRA is its limited human resource capacity to effectively fulfil its mandate. According to information provided to Spotlight by SAHPRA’s CEO Portia Nkambule in November 2018, SAHPRA then had 178 full-time employees and around a similar number of external evaluators supporting regulatory activities. SAHPRA is seeking to significantly increase its staff capacity to around 450 full-time staff over the next five years and has already initiated a hiring drive, advertising more than 100 new posts in May 2019. SAHPRA has further indicated that staff members were recently transferred from the National Department of Health’s Pharmaceutical Trade and Product Regulation programme to SAHPRA under a section 197 transfer agreement and, according to SAHPRA’s annual performance plan, the transferred staff will support core programmes responsible for medicines evaluation and registration and authorisation management.

While SAHPRA is seeking to strengthen staff capacity in all of its programmes, the 100 recently advertised posts included 17 new posts for medicines regulation and 19 posts for the backlog clearance project. A key goal of SAHPRA is to build its internal capacity to fulfil its medicines regulatory functions, unlike the MCC which relied heavily on external evaluators. SAHPRA’s annual performance plan explains that its reliance on a “dwindling” number of external evaluators creates difficulties in managing and optimising regulatory decision times due to the lack of contractual performance agreements with external evaluators. The annual performance plan clarifies that while SAHPRA hopes to absorb some external evaluators as internal staff, it will also seek to build its internal capacity through upskilling existing staff and recruiting new staff – but notes challenges in attracting and recruiting new internal evaluators.

SAHPRA did not respond to requests for more information on the difficulties it is facing in recruiting new internal evaluators. However, recruiting challenges faced by SAHPRA may include challenges identified by regulatory authorities in other jurisdictions – such as shortages of required skills in the domestic labour market and difficulties in competing with higher salaries offered by the industry.

Opportunities and challenges for public engagement

SAHPRA has taken significant and commendable steps since its establishment in February 2018 in outlining reform plans and processes to improve its functioning to effectively fulfil its mandate. In addition to the adoption and initiation of a strategy to address the regulatory backlog and its efforts to build its staffing capacity, SAHPRA has developed plans to digitise key processes and implement a new fees model (among other interventions). These steps have been taken despite significant challenges faced by the new regulatory agency in its first year of operations, including staff protests and the closure of its offices in the Civitas building due to unsafe working conditions.

While SAHPRA should be commended for its important work to date, responsiveness to the public and accountability remains a challenge despite the regulators commitments to improving and demonstrating transparency and accountability. Health NGOs in South Africa continue to express frustration due to the non-responsiveness of the regulator following requests for information and engagement. Additionally, despite questions Spotlight sent SAHPRA for this article, no responses were received.

In December 2018, SAHPRA CEO Nkambule noted that the regulatory authority was seeking to create a culture of transparency and that in the current transitional phase it would prioritise the implementation of a formal communications strategy and systems. SAHPRA’s annual performance plan notes that a communications strategy has been drafted and has been approved to be implemented during 2019. The plan further adds that through implementing the communications strategy, SAHPRA will endeavour to (among other goals) “develop mechanisms to allow all stakeholders to communicate easily with the regulator including being able to lodge queries and complaints”.

Beyond the implementation of a communications strategy, the Minister of Health should introduce legislative reforms to require greater transparency and accountability from SAHPRA. Vawda and Gray recently undertook a review of secrecy provisions contained in section 34 of the Medicines and Related Substances Act No 101 of 1965 and concluded that section 34 “violates the right to access to information in section 32 of the Constitution of SA”. They added that section 34 “appears to grant the MCC/SAHPRA unfettered authority to refuse access to information, except on limited grounds, based on its sole discretion”. Vawda and Gray recommended the amendment of section 34 to accommodate the right to access to information and added that the regulatory reform processes underway “provides an opportunity to redress a serious anomaly in our regulatory framework, and to align it with our constitutional paradigm, in order to reflect greater openness, transparency and accountability in our public institutions”.

As SAHPRA moves forward with the development and implementation of plans to re-engineer the authority, there is significant scope for civil society to monitor developments to demand meaningful transparency and accountability from the regulator (including necessary regulatory reforms) and ensure that the development and implementation of reforms serve the public interest.