South African Health Products Regulatory Authority Research Articles

Navigating regulatory landscape: A qualitative exploration of medical devices and in vitro diagnostic medical devices oversight in Zimbabwe through key stakeholder perspectives.

Medical devices and In Vitro Diagnostics (IVDs) are vital for public health and accessible healthcare. Still, there is an imbalance in high-quality products in Low and Middle-Income Countries (LMICs). Zimbabwe's regulatory framework for medical devices and IVDs is unclear, leading to ineffective compliance and surveillance. As a result, there are knowledge gaps regarding pre-market and post-market regulatory elements to ensure the safety, quality and performance of medical devices and IVDs used in Zimbabwe. Our study aimed to explore the current status of medical devices and IVD regulations in Zimbabwe. Semi-structured interviews were conducted with 12 regulators from the Medicines Control Authority of Zimbabwe (MCAZ) National Microbiology Reference Laboratory (NMRL), Medical Laboratory and Clinical Scientists Council (MLCScCZ) to understand the current status of medical devices and IVD regulations in Zimbabwe. Three participants completed a questionnaire to understand the regulatory landscape in Zimbabwe. Three key informant interviews were conducted with three regulators from the South African Health Products Regulatory Authority (SAHPRA), Tanzanian Medicines and Medical Devices Authority (TMDA), and World Health Organization Regulatory Systems Strengthening (WHO RSS) to learn best practices to create a roadmap for Zimbabwe. We analyzed qualitative data using a thematic analysis. The findings reveal significant deficiencies and gaps in the legal framework for regulating medical devices and IVDs, highlighting the need for a legal framework and the absence of more comprehensive regulations. Regulatory entities face capacity limitations, especially in regulating medical devices and IVDs. Conformity assessment processes, medical devices, IVD classification criteria, and post-market surveillance also represent challenges, highlighting the need for a well-defined framework and regulatory procedures. The Zimbabwean regulatory system pathway is reactive, prompting several regulatory initiatives to address needs. Despite facing challenges, there is recognition of the importance of collaboration among regulatory authorities, emphasizing a shared commitment to improving and strengthening medical devices and IVD regulations for improved patient safety. By advocating for a proactive, comprehensive, and legally sound approach, indicating the potential for collaboration and synergy, this study provides a foundation for well-informed policy recommendations to guide enhancements and build a framework for a resilient, efficient, and transparent regulatory environment in the Zimbabwe and African regions as a whole.

Evaluation of the impact of reliance on the regulatory performance in the South African Health Products Regulatory Authority: implications for African regulatory authorities.

The World Health Organization (WHO) advocates the use of reliance practices to enable national regulatory authorities (NRAs) to improve patients' access to medicines. This study considered whether reliance review translates into swifter medicine authorization. Abridged review outcomes were examined for New Chemical Entity (NCE) and generic applications to the South African Health Products Regulatory Authority (SAHPRA) in Chemistry, Manufacturing and Controls (CMC) and clinical/bioequivalence (BE), as well as overall NCE authorization times. SAHPRA NCE CMC review time was 91 days (abridged) vs. 179 days (full), applicant response time was 34 vs. 105 days, respectively, and there was a >2-fold time reduction for abridged vs. full CMC review (125 vs. 284 days). There was a 99-day decrease in clinical approval time through an abridged review (230 vs. 329 days) and a decrease in marketing authorization time for NCE abridged assessment (446 vs. 619 days). SAHPRA review time for generic applications was 97 days (abridged) vs. 191 days (full); applicant response time was 26 days (abridged) vs. 81 days (full) and there was a >2-fold time reduction for CMC and BE abridged vs. full review (122 vs. 272 days). These results clearly support World Health Organization recommendations for the use of reliance-based regulatory review to expedite the worldwide availability of safe, effective and needed medications.

Profile of adverse drug reaction reports in South Africa: An analysis of VigiBase® for the year 2017.

The South African Health Products Regulatory Authority (SAHPRA) monitors the safety of health products by collecting and evaluating adverse drug reaction (ADR) reports submitted by healthcare professionals, patients and pharmaceutical companies. The reports are shared with the World Health Organization (WHO) Programme for International Drug Monitoring. A demographic and clinical profile of ADR reports will improve our understanding of ADR reporting in South Africa to enhance training of reporters at all levels. This study describes the demographic and clinical profile of spontaneous ADR reports received by the SAHPRA during the year 2017. A retrospective, cross-sectional study was conducted to describe all ADR reports submitted by South Africa to VigiBase®, the WHO global database of Individual Case Safety Reports (ICSRs), during 2017. The demographic profile included patient characteristics (age and sex), type of reporter and the vigiGrade™ completeness score for each ICSR. The clinical profile included characteristics of the case, medicine(s) and reaction(s). A total of 8 438 reports with a mean completeness score of 0.456 (SD = 0.221) were assessed. Females and males represented 61.96% and 33.05% of cases, respectively (if sex was reported). All age groups were represented; however, 76.28% involved adults (aged 19-64 years). Physicians submitted the most reports (39.66%). Consumers were the reporters in 29.39% of cases. Pharmacists submitted only 4.45% of the reports. Anti-infective medicines were the most reported Anatomical Therapeutic Class (20.08%), while Human Immunodeficiency Virus was the top indication reported (10.27%). The highest number of MedDRA preferred terms used to describe reactions belonged to the System Organ Class, general disorder and administration site conditions. In 55.87% of the reports, the cases were reported as serious and 12.47% fatal. Death was the most reported MedDRA preferred term used to describe a reaction (5.17%). This was the first study that described ADR reports received by SAHPRA and improves our understanding of reporting in the country. The core clinical elements that are important in signal detection were often not included in reports. The findings demonstrated that patients were more active contributors to the national pharmacovigilance database than pharmacists. Reporters should be trained in pharmacovigilance and ADR reporting processes to increase the quantity and completeness of reports.

Trends in the utilization of medicines sold in the private sector post- registration in South Africa and the implications for similar countries

BackgroundRegulatory authorities register medicines for patients to access them within a reasonable period of time. There is a paucity of available data regarding the extent to which registered medicines reach the public after market authorisation is granted by the South African Health Products Regulatory Authority (SAHPRA). This is important since time spent by SAHPRA assessing medicines that are subsequently not launched onto the South African market means time wasted, which could be spent on assessing new medicines that address an unmet need in the country. Consequently, we initially analysed the time taken for registered medicines to reach patients and the relationship between medicines registered at SAHPRA and those subsequently dispensed in private pharmacies. The extent of registration of multiple sourced versus new patented medicines was also explored.MethodsA retrospective, descriptive and quantitative investigation was conducted for medicines registered between 2014 and 2019. Registered and dispensed medicines were compared to establish accessibility post registration. Data sources included SAHPRA and IQVIA datasets. Microsoft Excel and SAS were used for data storage, analysis, and computation of descriptive statistical analysis.ResultsOf (N = 2175) registered medicines, only 358 (16.5%; 95% CI 15.0%—18.1%) were dispensed to patients, and out of 1735 medicines registered between 2015 and 2019, only 57 (3.3%; 95% CI 2.5%—4.2%) were dispensed during the study period. Medicines acting on the central nervous system were registered and dispensed the most at 21.0% and 18.0%, respectively, whereas antineoplastic and immunomodulation agents were registered and dispensed only 11% and 5%, respectively. A concern was that only 13.0% of registered medicines were originators, with most either as generics, including branded generics, or pseudo-generics.ConclusionRegulatory measures should be implemented to ensure increased medicine access post-registration for new originators, especially for priority disease areas that benefit patients. Mental health diseases and improved access to oncology medicines require special attention and further investigation in South Africa.

The completeness of adverse drug reaction reports in South Africa: An analysis in VigiBase®.

Spontaneous reporting is regarded as a cornerstone of pharmacovigilance (PV) but presents many limitations, including varying quality and completeness of information, which is essential for causality assessment. This study aimed to evaluate the completeness of adverse drug reaction (ADR) reports in South Africa based on the vigiGrade completeness score. The South African Health Products Regulatory Authority (SAHPRA). A cross-sectional, descriptive study of all reports received by SAHPRA and submitted to VigiBase® in 2017 was conducted. A report with a vigiGrade score 0.8 is considered well-documented. The mean completeness score for the 8438 reports received was 0.456 (s.d. = 0.221). Only 11.3% of reports had a completeness score 0.8. The completeness of reports submitted by consumers professionals did not significantly differ from reports by physicians, pharmacists or other healthcare professionals (d ≤ 0.2). Reports of reactions that resulted in death (M = 0.572, s.e. = 0.007), disability (M = 0.491, s.e. 0.033) or were life threatening (M = 0.474, s.e. = 0.013) had a medium to large practically significant effect (0.5 ≥ d ≤ 0.8) on the completeness score compared with reports of congenital anomaly (M = 0.348, s.e. = 0.089). The completeness of reports submitted by consumers is comparable to those submitted by healthcare professionals. The completeness of reports was low and multiple measures to improve reporting are recommended.Contribution: This study describes the completeness of ADR reports in South Africa and the results can be used to improve training.

The Implementation of a Risk-Based Assessment Approach by the South African Health Products RegulatoryAuthority (SAHPRA).

An extensive backlog of pending regulatory decisions is one of the major historical challenges that the South African Health Products Regulatory Authority (SAHPRA) inherited from the Medicine Control Council (MCC). Revising and implementing new regulatory pathways is one of the strategic mechanisms that SAHPRA employs to circumvent this problem. To alleviate the backlog, the use of a new review pathway termed the risk-based review on the scientific quality and bioequivalence assessments was explored. The objective of the study was to articulate the risk-based assessment (RBA) pathway, to determine robust criteria for the classification of the levels of risk for medicines, and to define the improved process to be followed in the assessment and approval of medicines. In 2015, an extensive exercise was conducted by SAHPRA to identify the unknown status of in-process applications. The RBA pilot project commenced in 2016 and further piloted in 2021 using the knowledge gained from the 2016 study for optimisation of efficiency. By 2015 the backlog was quantified as 7902 applications in the pre-registration phase. The 2015 project entailed two phases. The initial phase was conducted to identify the status of 3505 in-process applications, which resulted in the registration of 198 applications. The second phase commenced in 2016 on 4397 applications not yet reviewed whereby the RBA approach was explored. With the developed criteria for risk classification and refined end-to-end registration process, the pilot resulted in a finalisation time with a median value of 90 calendar days and a median approval time of 109 calendar days. The throughput of the RBA pilot study conducted in 2021 was 68 calendar days finalisation time for the 63 applications used. These finalisation times are lower in comparison to the 501 calendar days for the current process employed by SAHPRA for the backlog clearance programme initiated in 2019. Both the 2016 and 2021 studies had similar approval times calculated from the date of allocation of scientific assessments. The reported evaluation timelines for both studies were within 6-7 h for a low-risk quality assessment, 9-10 h for a high-risk quality assessment, 7-8 h for a bioequivalence assessment, and 2-3 h for a biowaiver and initial response assessment. The refined processes used in the risk-based pilot studies to alleviate the SAHPRA backlog are described in detail. The process managed a reduction of the finalisation time to 68 calendar days in comparison to 501 calendar days for the current process that was employed by SAHPRA for the backlog clearance programme initiated in 2019. The RBA approach, therefore, reduces the finalisation and approval times for quality and bioequivalence assessments for regulatory authorities without compromising on the quality, safety and efficacy of the medicinal products. In addition, the approach provides a prototype solution to counteract the influx of medicinal product applications received by the regulatory authorities.

INSTIs for the management of HIV-associated TB (INSIGHT study): a phase 2b study to evaluate the efficacy, safety and pharmacokinetics of a combination of bictegravir, emtricitabine and tenofovir alafenamide fumarate for the treatment of HIV-1 infection in patients with drug-susceptible tuberculosis on a rifampicin-based treatment regimen: a phase 2b open-label randomised controlled trial

IntroductionCotreatment of HIV and tuberculosis (TB) reduces morbidity and mortality in coinfected patients. Availability of antiretroviral treatment (ART) drug options, including within drug classes, is important, particularly in high HIV/TB...

Bioequivalence Common Deficiencies in Generic Products Submitted for Registration to the South African Health Products Regulatory Authority (SAHPRA).

The cost of healthcare has become expensive globally, of which the greater part of the money is spent on buying innovator medicines. In order to make medicine affordable, the development of generic medicines has become paramount. The science of bioequivalence studies of generic products to demonstrate therapeutic equivalence with innovator products has been developed over the last 50years. These studies cost far less as compared to innovator products thereby reducing the cost of medicines. Accelerating access to medicines has become an increasing challenge due to insufficient resources from regulatory authorities, while pharmaceutical industry continues to expand. An investigation on the deficiencies identified during scientific assessments by SAHPRA in submitted bioequivalence studies is therefore paramount. Identification and publication of these deficiencies will assist in accelerating the access of medicines to patients. The aim of the study is to investigate the types and frequency of the common deficiencies observed in the bioequivalence section of generic submissions to SAHPRA. The study was conducted retrospectively over a 7-year period (2011-2017) for generic products that were finalised by the Pharmaceutical and Analytical pre-registration Unit. A more recent analysis on common deficiencies witnessed for applications assessed between 2020 and 2021 was also done to illustrate the consistency in the evaluation practises adopted by SAHPRA. There were 3148 applications finalised between 2011 and 2017, and to attain a representative sample for the study, statistical sampling was conducted. The multi-stage sampling called stratified systematic sampling was selected as the method of choice. The sample size was obtained using the statistical tables found in the literature and confirmed by a sample size calculation resulting in the selection of 325 applications (Fig. 2a). Additionally, 300 master applications were assessed between 2020 and 2021 for up-to-date data (Fig. 2b). All the deficiencies were collected and categorised according to the ICH E3 guideline and components relevant to biostudies. A total of 2458 deficiencies were collected from the selected sample size for applications finalised between 2011 and 2017 where a biostudy was submitted. The majority of the identified deficiencies were from the following categories; in vitro dissolution testing and specifications (18%), study design (17%), details on the test and reference products (16%), issues on sample analysis (16%), and statistical analysis (10%) (Fig. 3). From the applications assessed in 2020-2021, 492 deficiencies were identified with a similar trend compared to those finalised between 2011 and 2017. Comparison of the deficiencies with those reported by the USFDA and WHO PQTm is discussed with similarities outlined. The five most common deficiencies observed were extensively discussed. The outcomes of this study will guide pharmaceutical companies, sponsors, and Clinical Research Organisations (CROs) in submitting quality biostudies which will reduce turnaround times for registration and accelerate access to medicines for patients. In addition, the deficiencies identified will assist assessors from the different regulatory authorities to improve on their bioequivalence assessment.

Access to flucytosine for the treatment of HIV-associated cryptococcal meningitis in Africa

Cryptococcal meningitis, a major cause of meningitis in adults living with HIV infection, accounts for 15% of global HIV-associated mortality. 1 Rajasingham R Smith RM Park BJ et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017; 17: 873-881 Summary Full Text Full Text PDF PubMed Scopus (973) Google Scholar Treatment of cryptococcal meningitis involves three phases: induction, consolidation, and maintenance. The induction phase, which aims at reducing cerebral and meningeal fungal burden crucial for early survival, requires combination antifungal therapy and management of increased cerebrospinal fluid intracranial pressure. WHO in 2018 recommended at induction either 1-week amphotericin B deoxycholate plus flucytosine followed by high-dose fluconazole or 2-week oral fluconazole plus flucytosine. 2 WHOGuidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-infected adults, adolescents and children. Supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. https://www.who.int/publications/i/item/9789241550277Date: 2018 Date accessed: April 14, 2022 Google Scholar However, in the absence of flucytosine, fluconazole plus amphotericin B deoxycholate could be an alternative. The Advancing Cryptococcal Meningitis treatment for Africa trial on which these recommendations were based showed flucytosine to be a better drug at reducing mortality than is fluconazole in combination with amphotericin B deoxycholate. 3 Molloy SF Kanyama C Heyderman RS et al. Antifungal combinations for treatment of cryptococcal meningitis in Africa. N Engl J Med. 2018; 378: 1004-1017 Crossref PubMed Scopus (176) Google Scholar In a recent trial, a combination of single dose 10 mg/kg liposomal amphotericin B and 2-week flucytosine plus fluconazole showed non-inferiority and tolerance benefits to previously recommended induction therapy. 4 Jarvis JN Lawrence DS Meya DB et al. Single-dose liposomal amphotericin B treatment for cryptococcal meningitis. N Engl J Med. 2022; 386: 1109-1120 Crossref PubMed Scopus (9) Google Scholar These trials and some observational studies 5 Dromer F Mathoulin-Pelissier S Launay O Lortholary O French Cryptococcosis Study GDeterminants of disease presentation and outcome during cryptococcosis: the CryptoA/D study. PLoS Med. 2007; 4: e21 Crossref PubMed Scopus (280) Google Scholar provide data that confirm flucytosine as an important drug combination for inductive treatment of cryptococcal meningitis. However, access to this old, off patent drug is not guaranteed in Africa, South America, and Asia where the burden of cryptococcal meningitis is highest. 6 Loyse A Dromer F Day J Lortholary O Harrison TS Flucytosine and cryptococcosis: time to urgently address the worldwide accessibility of a 50-year-old antifungal. J Antimicrob Chemother. 2013; 68: 2435-2444 Crossref PubMed Scopus (83) Google Scholar In South Africa, a region with a long-standing high burden of cryptococcal meningitis, flucytosine was only registered in December, 2021, by the South African Health Products Regulatory Authority (SAHPRA) despite the application being submitted 2 years previously by Viatris. 7 Application for WHO Model List of Essential Medicines: flucytosine (5FC). http://www.life-worldwide.org/assets/uploads/files/Flucytosine_63_CORE_AC.pdfDate: 2018 Date accessed: April 24, 2022 Google Scholar Outcomes of flucytosine-containing combination treatment for cryptococcal meningitis in a South African national access programme: a cross-sectional observational studyIn-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit. Full-Text PDF

Common deficiencies found in generic Finished Pharmaceutical Product (FPP) applications submitted for registration to the South African Health Products Regulatory Authority (SAHPRA)

BackgroundThe aim of the study was to investigate the common deficiencies observed in the Finished Pharmaceutical Product (FPP) section of generic product applications submitted to SAHPRA. The study was conducted retrospectively over a 7-year period (2011–2017) for products that were finalised by the Pharmaceutical and Analytical pre-registration Unit.MethodsThere were 3148 finalised products in 2011–2017, 667 of which were sterile while 2089 were non-sterile. In order to attain a representative sample for the study, statistical sampling was conducted. Sample size was obtained using the statistical tables found in literature and confirmed by a sample size calculation with a 95% confidence level. The selection of the products was according to the therapeutic category using the multi-stage sampling method called stratified-systematic sampling. This resulted in the selection of 325 applications for non-sterile products and 244 applications for sterile products. Subsequently, all the deficiencies were collected and categorised according to Common Technical Document (CTD) subsections of the FPP section (3.2.P).ResultsA total of 3253 deficiencies were collected from 325 non-sterile applications while 2742 deficiencies were collected from 244 sterile applications. The most common deficiencies in the FPP section for non-sterile products were on the following sections: Specifications (15%), Description and Composition (14%), Description of the Manufacturing Process (13%), Stability Data (7.6%) and the Container Closure System (7.3%). The deficiencies applicable to the sterile products were quantified and the subsection, Validation and/or Evaluation (18%) has the most deficiencies. Comparison of the deficiencies with those reported by other agencies such as the USFDA, EMA, TFDA and WHOPQTm are discussed with similarities outlined.ConclusionsThe overall top five most common deficiencies observed by SAHPRA were extensively discussed for the generic products. The findings provide an overview on the submissions and regulatory considerations for generic applications in South Africa, which is useful for FPP manufacturers in the compilation of their dossiers and will assist in accelerating the registration process.

What’s new for the clinician – summaries of recently published papers

To date, very few treatments have been demonstrated to reduce the burden of morbidity and mortality from COVID-19. Although corticosteroids have been proven to reduce mortality in severe disease, there has been little convincing evidence on interventions that may prevent disease, reduce hospitalizations, and reduce the numbers of people progressing to critical disease and death. Ivermectin is a well-known medicine that is approved as an antiparasitic by the World Health Organization and the US Food and Drug Administration. It is widely used in lowand middle-income countries to treat worm infections. Also used for the treatment of scabies and lice, it is one of the World Health Organization’s Essential Medicines.1 With total doses of ivermectin distributed apparently equalling one-third of the present world population,1 ivermectin at the usual doses (0.2–0.4 mg/kg) is considered extremely safe for use in humans.1 In addition to its antiparasiticactivity, it has been noted to have antiviral and anti-inflammatory properties, leading to an increasing list of therapeutic indications. South African authorities approved the use of a drug used to control parasites in humans and livestock to treat coronavirus patients. Additionally, in January 2021, the South African Health Products Regulatory Authority (SAHPRA) announced that ivermectin, would be allowedfor use on compassionate grounds in a controlled-access program. Ivermectin locally has been used for the prevention and/or management of Covid-19 infection. This has resulted in a huge black market trade of ivermectin in South Africa as many health professionals and others have taken to social media and other platforms to profile this drug as an effective treatment for the covid-19 viral infection. Roman and colleagues (2021)1 conducted a systematic review and meta-analysis to evaluate treatment effects of Ivermectin (IVM) on clinical outcomes and adverse events (AEs) in people with COVID-19.

South African Regulatory Authority: The Impact of Reliance on the Review Process Leading to Improved Patient Access.

Background: The aims of this study were to compare the overall regulatory review timelines achieved by the South African Health Products Regulatory Authority (SAHPRA) in 2020 to the timelines historically achieved by the Medicines Control Council (MCC). This study also aimed to evaluate the regulatory review processes and the good review practices that have been implemented by SAHPRA to support the assessment of new chemical entities and generic product applications for market authorization in the business-as-usual and backlog process streams. Methods: A questionnaire was completed and verified by SAHPRA to describe the structure of the organization, the resources available, the process for regulatory review of new chemical entities and generic products and the level of implementation of good review practices and regulatory decision-making practices for market authorization. Data were collected and analyzed on the overall approval timelines for new chemical entities and generic products registered by SAHPRA in 2020 in the business-as-usual and backlog process streams. Results: A full, independent scientific review was conducted for all new chemical entities and generic product applications in the business-as-usual stream. Facilitated regulatory pathways were introduced for the review of new chemical entities and generic products in the backlog stream. As a result, the timelines for approval of applications in the backlog stream were 68% quicker for both new chemical entities and generics, using facilitated regulatory pathways, such as abridged and verification review models. Conclusion: The comparisons made through this study provided insight into the improvements that have been made through the establishment of SAHPRA and the transition in 2018 from the MCC. The re-engineered processes that have been developed and implemented by SAHPRA to address the backlog in the review of the applications for market authorization have demonstrated a decrease in the overall median approval times. The expansion of these processes into the routine review of medical products will contribute to the enhanced regulatory performance of SAHPRA and patients’ access to new medicines.

SAHPRA - Relevance of the New South African Health Products Regulatory Authority and Opportunities Ahead

Regulatory environments are constantly evolving, and South Africa has witnessed some significant developments in the recent past. Operational launch of the South African Health Products Regulatory Authority (SAHPRA) as new healthcare products regulator marks a key milestone in the establishment of international standards in regulatory practices. Both the Medicines Control Council (MCC) and the Directorate of Radiation Control (DRC) were replaced by SAHPRA to bring control of medicines, medical devices, in vitro diagnostic tests and devices, and radiation emitting products under one regulatory body. The new agency was instituted under schedule 3A of Public Finance Management Act as public entity, thereby enabling it to retain the revenue generated. The change has evidently impacted the regulatory practices positively; however, the challenges inherited by regulators and those regulated are enormous. SAHPRA needs to confront the challenges and make the most out of the opportunities ahead. This study aims to focus on understanding the new agency, its evolution over time, objectives set forth, organizational and operational construct, responsibilities, accomplishments so far, outstanding challenges, opportunities ahead, and the collaborative efforts that can support its operation. SAHPRA has had noteworthy achievements as a healthcare products regulator. By making most use of collaboration efforts SAHPRA is all set to work through the challenges and gain from opportunities. https://doi.org/10.21423/jrs-v09i2dureja

Ivermectin and the rule of law

The ivermectin saga has taken on a new dimension: respect for the rule of law by the state. The rule of law is important, as it is a cornerstone of our democratic Constitutional order. The South African Health Products Regulatory Authority (SAHPRA) has a statutory mandate to regulate medicines and related substances, but it also has a constitutional duty to obey the law. This duty includes obeying court orders. However, SAHPRA appears to have contravened the consent order handed down by the Pretoria High Court on 2 February 2021, and therefore undermined the rule of law. This situation is untenable in our democratic Constitutional order.

A Proposed Regulatory Review Model to Support the South African Health Products Regulatory Authority to Become a More Efficient and Effective Agency.

Background: National regulatory agencies of various sizes and maturity levels, including the South African Health Products Regulatory Authority (SAHPRA), have had to revise systems and re-engineer processes in order to adapt to the new regulatory environment and increase the effectiveness of regulatory operations. This study aimed to develop a new regulatory review model for improved regulatory performance, underpinned by the parameters of the World Health Organization Global Benchmarking Tool (WHO GBT) that support strengthening of regulatory systems. Methods: A new enhanced model for regulatory review, was developed based on the key recommendations from 6 studies, previously conducted by the authors, that were identified as fundamental elements in enhancing regulatory performance. The elements selected to define the new regulatory review model were endorsed through the integration of the parameters of the WHO GBT that, when embedded within regulatory systems, support enhanced regulatory performance. Results: Opportunities for improvement in regulatory performance were identified and include quality measures; monitoring and evaluating review times; a risk-based evaluation; transparency and communication; and training and education. An improved model for the South African regulatory review and benefit-risk (BR) assessment supported by quality decision-making was proposed as well as recommendations for the application of risk-stratification strategies, strengthening of reliance networks, reinforcing good regulatory practices (GRPs) and enhancing transparency. Conclusion: If implemented the proposed improved regulatory model may pave the way towards more efficient and transparent, streamlined review processes, coupled with increased consistency, evidence-based decision-making practices, reduced timelines and improved patients’ access to new medicines in South Africa.

Assessing the safety and pharmacokinetics of the anti-HIV monoclonal antibody CAP256V2LS alone and in combination with VRC07-523LS and PGT121 in South African women: study protocol for the first-in-human CAPRISA 012B phase I clinical trial

IntroductionNew HIV prevention strategies are urgently required. The discovery of broadly neutralising antibodies (bNAbs) has provided the opportunity to evaluate passive immunisation as a potential prevention strategy and facilitate vaccine...

‘It’s like making your own alcohol at home’: Factors influencing adolescent use of over-thecounter cough syrup

Background. Adolescents are increasingly experimenting with new ‘craze drugs’, including over-the-counter cough medicine (OTCCM). However, there is limited empirical evidence regarding South African (SA) adolescents’ use of codeine-containing medicines, especially OTCCMs. Objective. To describe SA adolescents’ views of OTCCM misuse, and the factors that may promote its use. Methods. The research adopted an exploratory qualitative design. Focus group discussions ( N =24) were conducted with 144 learners between 14 and 17 years old in two township communities in SA. Data were analysed thematically supported by Atlas.ti. Results. Three core themes emerged from the analysis, namely knowledge of OTCCM use; factors that influence OTCCM use; and effects of OTCCM use. Participants reported that young people use OTCCM recreationally. Four main factors were noted to influence OTCCM misuse in their communities, namely accessibility, affordability, social influences and the clandestine appeal of cough medicine. Adolescents also said that OTCCM had similar euphoric effects to alcohol or marijuana, but could not readily describe any negative impact. Conclusion. This exploratory study with adolescent participants provides contextualised empirical evidence about OTCCM. The findings call for the South African Health Products Regulatory Authority (SAHPRA) to promptly consider pending regulations on OTC codeinecontaining medication and demands increased awareness of codeine misuse in communities.

Testing the regulatory framework in South Africa \u2013 a single-blind randomized pilot trial of commercial probiotic supplementation to standard therapy in women with bacterial vaginosis

BackgroundBacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes. Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment.MethodsWomen with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7–10) but STI- women were randomized to vaginal metronidazole alone (n = 12) or to metronidazole followed by a commercial oral/vaginal probiotic (n = 18). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent≤3) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment.ResultsThe South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR = 0.52, 95% CI = 0.24–1.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1α concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product.ConclusionNavigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered.Trial registrationThis trial was registered on 17 October 2017 with the South African National Clinical Trial Register (http://www.sanctr.gov.za/; BV-trial1; DOH-27-1117-5579).

Medical cannabis: What practitioners need to know.

The South African (SA) Constitutional Court recently decriminalised the private cultivation, possession and use of cannabis by adults. Cannabis contains varying amounts of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), depending on various cultivation factors. No commercial plant-derived cannabis products are currently registered by the SA Health Products Regulatory Authority (SAHPRA) for medical use. Such products are therefore unregulated, but are freely available in SA, and may be of inadequate quality and unverified composition, and not guaranteed to be safe or effective. SAHPRA has to date approved only one synthetic medical cannabis product, dronabinol. Evidence supporting benefit from medical cannabis exists for two drug-resistant childhood forms of epilepsy, Dravet syndrome and Lennox-Gastaut syndrome. Adjuvant therapy with medical cannabis can reduce seizure frequency for Lennox-Gastaut syndrome and Dravet syndrome by 18.8% and 22.8%, respectively, and may be beneficial for other rare forms of epilepsy. There is moderate evidence for chemotherapy-induced nausea and vomiting with the synthetic cannabinoids. Multiple sclerosis-associated spasticity showed a small clinical improvement in self-reported spasticity when a purified form of THC/CBD was added to existing therapy. Currently, low-level or no convincing evidence exists for the use of medical cannabis for chronic pain, sleep and weight disorders, and neuropsychiatric disorders. Cannabis is associated with a greater risk of adverse effects than active and placebo controls, and may be involved in clinically significant drug-drug interactions. The evolving regulatory and legal landscape on the use of medical cannabis will guide prescription and recreational use in the coming years.

The South African Medicines Control Council: Comparison of Its Registration Process With Australia, Canada, Singapore, and Switzerland.

Introduction: Comparisons between regulatory authorities of similar size and regulatory characteristics facilitate value-added benchmarking and provide insight into regulatory performance. Such comparisons highlight areas for improvement as authorities move toward achieving their regulatory goals and stakeholders’ demands. The aims of this study were to compare the registration process and the regulatory review model of the South African Medicines Control Council (MCC) to that of four other similar-sized regulatory authorities and to identify areas for improvement that may inform recommendations to the South African Health Products Regulatory Authority (SAHPRA) as it looks to re-engineer and enhance the registration process in South Africa.Methods: A questionnaire describing the organisational structure, the registration process, good review and decision-making practices of the MCC was completed by the author (AK) for the purpose of this study and validated by the Registrar of the MCC. Similar questionnaires were also completed and validated by Australia’s Therapeutic Goods Administration (TGA), Canada’s Health Canada, Singapore’s Health Science Authority (HSA) and Switzerland’s Swissmedic.Results: A comparison of the MCC regulatory process with the four comparative agencies indicated that they all have similar requirements and employ a full-review model although the timelines for the MCC were considerably longer. However, similar quality measures were implemented by all authorities as part of their good review practices (GRevP) including prioritising transparency, communication, continuous improvement initiatives and training.Conclusion: Comparisons made through this study provided insight into the areas of the MCC registration process that may be improved and have informed recommendations to SAHPRA including the implementation of facilitated regulatory pathways, definition of targets for key milestones in regulatory review and formal implementation and monitoring of GRevP. In order to build quality into the review process the application of a standardised template for the clinical assessment of medicines such as the Universal Methodology for Benefit-Risk Assessment (UMBRA) could be considered as well as enhancing transparency and communication through the application of an electronic management system and the development of publicly available summaries for the basis of approval.