African Health Products Regulatory Authority Research Articles

Assessing the acceptability of, adherence to and preference for a dual prevention pill (DPP) for HIV and pregnancy prevention compared to oral pre-exposure prophylaxis (PrEP) and oral contraception taken separately: protocols for two randomised, controlled, cross-over studies in South Africa and Zimbabwe

IntroductionOral pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention method; however, uptake and persistence have been low among southern African women. A dual prevention pill (DPP) that combines PrEP...

The Case for Pre-Emptive Pharmacogenetic Screening in South Africa.

Lack of equitable representation of global genetic diversity has hampered the implementation of genomic medicine in under-represented populations, including those on the African continent. Data from the multi-national Pre-emptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE) study suggest that genotype guidance for prescriptions reduced the incidence of clinically relevant adverse drug reactions (ADRs) by 30%. In this study, hospital dispensary trends from a tertiary South African (SA) hospital (Steve Biko Academic Hospital; SBAH) were compared with the drugs monitored in the PREPARE study. Dispensary data on 29 drugs from the PREPARE study accounted for ~10% of total prescriptions and ~9% of the total expenditure at SBAH. VigiLyze data from the South African Health Products Regulatory Authority were interrogated for local ADRs related to these drugs; 27 were listed as being suspected, concomitant, or interacting in ADR reports. Furthermore, a comparison of pharmacogene allele frequencies between African and European populations was used to frame the potential impact of pre-emptive pharmacogenetic screening in SA. Enumerating the benefit of pre-emptive pharmacogenetic screening in SA will only be possible once we initiate its full application. However, regional genomic diversity, disease burden, and first-line treatment options could be harnessed to target stratified PGx today.

The regulation of health-related direct-to-consumer genetic tests in South Africa by the Medicines and Related Substances Act

This article examines the regulation of health-related direct-to-consumer genetic tests (‘HDGTs’) in South Africa by the Medicines and Related Substances Act 101 of 1965 and its related regulations, namely the Regulations Relating to Medical Devices and In Vitro Diagnostic Medical Devices and the draft Regulations Relating to Medical Devices, as well as the South African Health Products Regulatory Authority guidelines. Such regulation includes the classification, licensing, registration, marketing, labelling and importing of HDGTs. At a basic classification level, the manufacturer’s intention determines whether HDGTs are medical devices and/or in vitro diagnostic devices (‘IVDs’). Those HDGTs that are medical devices are also likely to be IVDs and are likely to be classified as Class B IVD medical devices, meaning that they pose low to medium risk. This is because the intended use of an HDGT is generally not as a diagnostic tool but as an informational tool, where the results are not definitive and additional testing is required. Accordingly, a licence is required to manufacture, import, export, sell or distribute HDGTs in South Africa. The classification of HDGTs also impacts the rules relating to labelling, advertising and importation.

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.

Extended safety and tolerability of subcutaneous CAP256V2LS and VRC07-523LS in HIV-negative women: study protocol for the randomised, placebo-controlled double-blinded, phase 2 CAPRISA 012C trial

IntroductionWomen-controlled HIV prevention technologies that overcome adherence challenges of available daily oral pre-exposure prophylaxis and give women a choice of options are urgently needed. Broadly neutralising monoclonal antibodies (bnAbs) administered...

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...

Perceptions, practices and barriers to reporting of adverse drug reactions among HIV infected patients and their doctors in 3 public sector hospitals of the Ethekwini Metropolitan, Kwa-Zulu Natal: a cross sectional and retrospective analysis

BackgroundAdverse drug reactions (ADRs) remain a global public health concern. Pharmacovigilance practises are essential in ensuring patients safety and post drug marketing surveillance. This study aimed to describe practices, perceptions and barriers towards ADR reporting practices amongst People Living with HIV/AIDS (PLWHA), who are on Highly Active Anti-Retroviral Therapy (HAART) and their doctors.MethodsThe study took place at 3 public sector hospitals. The first phase of the study was a quantitative cross-sectional study using a closed ended questionnaire that was given to PLWHA. Phase two was a retrospective analysis of these patients’ medical files, whilst phase 3 included a descriptive statistics to determine the frequencies and percentages for variables such as ADR reporting practices by doctors.ResultsSpontaneous reporting, was evident with 202 patients (48%) indicating that they reported experiencing ADRs to their doctors. Ten doctors (77%) indicated that they received PV training. Eight (62%) doctors indicated that the completed ADR reporting forms were submitted to the pharmacy manager in the hospital for forwarding to the regulatory authority, with 2 (15%) indicating that they submitted directly to the South African Health Products Regulatory Authority. Four (31%) doctors stated that the system of reporting ADRs is ineffective with the majority of the doctors 12 (92%) responding that the reporting of ADRs is very important/critical. A barrier cited by 4 patients (0.9%) for non-reporting of their ADRs was transport cost. Whilst doctors' barriers included reporting being time consuming (31%), and a lack of availability of reporting forms (31%).ConclusionPatients and doctors are reporting ADRs but more education and easier reporting process should be available to strengthen the knowledge and reporting of ADRs. Doctors agree that it is critical to report ADRs. Electronic reporting should be encouraged to lessen the time it takes to report ADRs.

Ivermectin exposures reported to the Poisons Information Helpline in South Africa during the COVID-19 pandemic

Ivermectin is an antiparasitic drug that has shown in vitro activity against COVID‑19. Clinical studies supporting ivermectin for COVID‑19 prevention and treatment are conflicting, with important limitations. Public support for ivermectin is significant, with extensive off-label use despite the conflicting views on its efficacy. Ivermectin tablets and injectable formulations are not registered in South Africa for human use by the South African Health Products Regulatory Authority. The National Department of Health does not currently recommend the use of ivermectin for COVID‑19. To describe cases of ivermectin exposure reported to the Poisons Information Helpline of the Western Cape (PIHWC) before and after publication of the drug's in vitro activity against SARS-CoV-2. In a retrospective review, ivermectin-related calls reported to the PIHWC from 1 June 2015 to 30 June 2020 (period 1) were compared with calls received from 1 July 2020 to 31 July 2021 (period 2), dichotomised according to the first publication indicating ivermectin activity against SARS-CoV-2. Seventy-one cases were screened, and 65 were included for analysis; 19 cases were reported during period 1 and 46 during period 2. During period 2, 25 ivermectin cases (54.3%) were related to COVID‑19 use. Of these, 24 cases (52.2%) involved veterinary preparations, 3 (6.5%) human preparations and 19 (41.3%) unknown preparations. Fourteen cases (73.7%) during period 1 and 30 (65.2%) during period 2 were reported to be symptomatic. The most common organ systems involved were the central nervous (n=26 cases; 40.0%), gastrointestinal (n=18; 27.7%), ocular (n=9; 13.8%) and dermatological (n=5; 7.7%) systems. Ivermectin-related exposure calls increased during study period 2, probably as a result of ivermectin being used as preventive and definitive therapy for COVID‑19 in the absence of robust evidence on efficacy, dosing recommendations or appropriate formulations.

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.

Dapivirine Vaginal Ring for HIV Prevention in Women in South Africa

Young women remain disproportionately affected by the HIV epidemic in South Africa. Clinical trials have shown that the dapivirine vaginal ring (DVR) is safe and effective at reducing HIV infection in women. In March 2022, the South African Health Products Regulatory Authority approved the use of the DVR in women aged 18 years and older who are unable or unwilling to use oral pre-exposure prophylaxis, as an additional choice for preventing HIV in women at substantial risk. Modelling studies have suggested that the DVR could have a substantial impact if prioritized for women at substantial risk of HIV or women aged 22–29 years. The licensing of the DVR in South Africa is a milestone event that brings the first long-acting and woman-controlled HIV prevention method another step closer to reaching the people who need it. As South Africa prepares its introduction, it is critical to examine the unmet need for HIV prevention and to review the clinical trial data that led to the DVR's approval.

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