Most essential medicines in South Africa are sourced through a centralized, open tendering process where contracts are entered into between the NDoH and suppliers of medicines, on behalf of all provinces. With the strategic use of market intelligence, improved competition and efficiencies associated with pooled volumes, low prices can be achieved (Pharasi and Miot, 2012).

Currently, the medicine supply chain in South Africa is characterized by limited planning activities, and outdated duplicative processes, with high variability among the provinces and districts. Additionally, storage infrastructure appears ill-equipped to fully service the growing disease burden and programme requirements of South Africa. This will change in the future with a number of planned developments, which are described below.

National contracts help leverage economies of scale to achieve price efficiencies by pooling the demand of all provinces. Currently, there is fragmentation in contracting due to a lack of standard processes and systems. A National Contract Management Unit (CMU) will monitor information aggregated through MPUs, who will be responsible for implementing tactical, uniform contract management protocols, as a shared service on behalf of the health facilities within their jurisdiction. The shared function between CMU and MPUs is already in place. However, it is recognized that this development will require agile institutional processes, capable of responding to the changing market dynamics to improve future contracting. Processes will be helped by the fact that the information gathered will be used to monitor agreed performance metrics, with pertinent changes implemented to improve future performance if needed.

The relevant MPUs will be responsible for implementing tactical, uniform contract management protocols, as a shared service on behalf of the health facilities within their jurisdiction.

Although, there are many interventions that are already underway, the complexity of the environment means that there is still a long way to go. Addressing root causes of current problems over the short, medium and long term, will require agile institutional processes, capable of responding to the changing market dynamics that are expected to accompany the implementation of NHI. The new strategy being implemented in South Africa aims to achieve a continued dependable supply and reliable payment for goods and services, improved process efficiencies and governance, predictable demand and reduced wastage. These changes will assist South Africa in servicing the growing patient needs, including those for NCDs, with the implementation of NHI in a responsive manner.

The overall intention is to improve the scrutiny over the current prices paid for medicines in South Africa with the development of a National Health Care Pricing Authority (Department National Treasury - Republic of South Africa, 2015) and a National Health Pricing Advisory Committee, which will be a ministerial advisory committee (MAC), within the implementation structures of the NHI (NDoH, 2017c). This is in addition to ensuring continued access to, and supply of, agreed medicines.

Surveillance systems for medicines include a visibility and analytics network, which consists of various dashboards including the assessment of medication availability at PHC and hospital level, and data triangulation, as well as prescribing data, guidelines and prices, to improve future medicine procurement and use.

Supplier performance measurement will be derived from the South African Pharma Deliveries Data, with performance scorecards as outputs measuring Lead Time, On Time and In Full (OTIF) deliveries coupled with timely monthly reporting. In addition, a Pipeline Analysis Tool (PAT) has been developed with the data submitted by suppliers on a fortnightly basis. The visibility of supply vs. demand from suppliers are reported with forward production planning for at least three months. An Age Analysis Tool (AAT) has also been developed with the data being supplied by suppliers giving an indication of outstanding debt for contracted items. The data will be triangulated with PMPU stock availability data as well as Hospital and PHC data to add robustness. This will now provide a proactive response in terms of stock outs and low stock holding to improve future supplies.

By July 2016, the surveillance systems covered all 3,400 PHC facilities in South Africa and two thirds of hospitals, with the initial focus on HIV, TB and vaccines. This is currently being expanded to other essential medicine items. A key lesson has been the essential need to establish a master procurement catalog and bar coding system for nation-wide roll out. Barcodes are seen as essential to track medicines through the value chain.

The CCMDD programme was initially implemented in ten NHI districts in February 2014. The Western Cape province was not included due to the fact that they already had implemented a similar programme (Magadzire et al., 2015). Due to the success of the CCMDD programme (Department of Health KZN, 2016b), it has since been rolled out to 46 districts across the other eight provinces. Each province has autonomy regarding the conditions to be managed through the CCMDD programme.

According to service provider reports, more than 1.7 million patients have been registered on the programme in the eight provinces. The NDoH has also appointed more than 650 external PuPs. Additionally, patients can also make use of Adherence Clubs and outreach PuPs to collect repeat medicines, and these collection points are managed by the various facilities (see Figure 3). As a result, access to, and use of, medicines within the public healthcare sector should appreciably improve.

Monthly statistics are now available to assist provinces and government in keeping track of the system and patients to improve future care. These include the following indicators:

Number of patients registered per facility/district/province

Additional indicators include the following:

Number of parcels delivered per PuP or per district/province

An alternative model for structured, safe, and reliable service delivery closer to a patient's workplace or home, is the Remote Automated Dispensing Units (RADUs) (Toit, 2017). However, only a few of these units are currently being piloted in South Africa, and it is too early to comment. In terms of future service delivery, the aim of this type of model is also to create a controlled method whereby chronic disease patients can, for example, have screening tests performed when they collect their chronic medicine parcels (Toit, 2017). This could be an opportunity for community pharmacies within the private healthcare sector to introduce an affordable model or service package, which could be purchased within the NHI system to improve access to medicines and healthcare (Toit, 2017).

The Standard Treatment Guidelines and Essential Medicine List (STGs-EML) have been developed in South Africa to ensure medicines are available which are safe, effective, and cost-effective, and promote the rational use of medicines (Gray et al., 2015; NDoH, 2015c; Sooruth et al., 2015; Perumal-Pillay and Suleman, 2016, 2017b). STGs-EML have been developed for all levels of healthcare, namely PHC (focusing on nurse-initiated treatment), hospital level guidelines for pediatrics and adults, and a tertiary/quaternary EML for specialist level (Pharasi and Miot, 2012), through their respective Expert Review Committees (ERCs). The ERCs are under the direction of the South African National Essential Medicines List Committee (NEMLC), and consist of key stakeholders relevant for their particular level of care, such as cardiologists for hospital level and nursing prescribers for the PHC level (Leong et al., 2015).

Key principles used in the development of the STGs-EML include evidence-based decision making, with criteria based on efficacy, safety, affordability, cost-effectiveness, and implications for practice. Evidence and final medicine selections are peer reviewed to enhance the robustness of decision making. The STGs-EML are reviewed by the ERCs on a three-yearly basis, with two opportunities in the process for South African healthcare workers to provide comments. Previously published in book format after the three year review process, completed chapters are now released on a mobile phone application, the EML Clinical Guide, allowing health care workers and patients immediate access to the latest medicines and guidelines in the public healthcare sector. This mobile application is now the primary reference source for healthcare workers to access the STGs-EML (Lancaster, 2016) with the increasing use of smart phones in South Africa. This is expected to enhance adherence to current guidelines, which has been variable in practice (Sooruth et al., 2015; Matsitse et al., 2017).

Recommendations for new medicines to be placed on the STGs-EML are received by the ERCs from provincial PTCs within hospitals or from ambulatory care clinics through their district PTCs. A recent comprehensive publication by Perumal-Pillay and Suleman documented that in recent years the number of suggested medicines for PHC facilities within the PHC STGs-EMLs has increased whilst the number has decreased for adult and pediatric EMLs (Perumal-Pillay and Suleman, 2016). Comprehensive interviews with key members of the NEMLC ascertained that the processes have changed over the years to become predominantly evidence-based (Perumal-Pillay and Suleman, 2017b). The quality, safety and efficacy of new medicines for potential inclusion are typically considered first followed by cost considerations (Perumal-Pillay and Suleman, 2017b), although affordability is still a major area for sustainability and access to all.

The development of guidelines with all key stakeholder groups can include criteria for use as well as criteria restricting the use of medicines to defined populations, including potential rationing criteria. The goal of the STGs-EML is enhanced by developing a well thought out and evidence-based list of key medicines, which is peer reviewed, to meet the needs of the population, similar to other countries including Spain, Sweden, and the United Kingdom (Norman et al., 2009; Gustafsson et al., 2011; Bjorkhem-Bergman et al., 2013).

Other healthcare systems have faced similar challenges to South Africa in terms of limited budgets and increased demand for healthcare (Jakovljevic et al., 2016). This has resulted in policies to enhance cost-effective prescribing among Western European countries, including enhancing the use of generics (Godman et al., 2014), to help maintain universal and comprehensive healthcare across populations. This is in contrast to Central and Eastern European (CEE) countries with high co-payments, with more limited public spending (Jakovljevic et al., 2016). Such divisions have resulted in for instance appreciably lower use of biological medicines to treat inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases among CEE vs. Western European countries (Putrik et al., 2014a,b; Kostic et al., 2017). The ongoing measures in South Africa, including chronic disease management programmes alongside NHI initiatives, should help address concerns seen among CEE countries.

With the implementation of NHI, the NDoH will be appointing a MAC on Health Technology Assessment (HTA). This multi-disciplinary committee will provide recommendations to the Minister of Health on the prioritization, selection, distribution, management and introduction of interventions for health promotion, disease prevention, diagnosis, treatment, and rehabilitation (NDoH, 2017c). Part of this will include the creation of a South African HTA Agency (NDoH, 2017c). The MAC-HTA will be involved in both investment and disinvestment decisions, similar to agencies in other countries (Parkinson et al., 2015; Guerra-Junior et al., 2017).

Improved access to medicines will in future be strengthened in terms of efficiency by the use of innovative technology to support the selection of medicines, formulary management, standard treatment regimens for prescribers, rational medicine use interventions, and adherence support. An integrated online platform, Essential Medicines Electronic Access (EMelA), currently under development will be integrated with various electronic platforms, including electronic prescribing and dispensing tools, patient management systems and stock management systems (Figure 5).

Alongside these changes, there will be ongoing programmes to enhance compliance to the STGs. This includes possibly educational and other activities including pharmacists and other key stakeholders where there are concerns with prescribing, which is likely to include academic detailing similar to other countries (Costa et al., 2016). Ongoing research programmes will include seeking ways to further improve compliance to prescribing guidance to improve future care where there are identified concerns (Sooruth et al., 2015; Matsitse et al., 2017). Instigation of electronic prescribing and monitoring of prescriptions against agreed guidance will also enhance future adherence to prescribing guidance, as seen for instance with the “Wise List” in Stockholm County Council in Sweden (Gustafsson et al., 2011; Bjorkhem-Bergman et al., 2013; Eriksen et al., 2017).

With growing numbers of patients accessing treatment for HIV, TB, and NCDs, adherence increasingly becomes a challenge for all patients with chronic diseases (Rampamba et al., 2017). Despite South Africa having the largest ARV treatment programme in the world, with generally better adherence rates in sub-Saharan Africa compared with North America (Binagwaho and Ratnayake, 2009), challenges such as declining retention in care rates, and increased drug resistance due to poor adherence among some patients and poor programme performance are evident (Awolola et al., 2014; Baloyi et al., 2014; Ramdas et al., 2015; Vagiri et al., 2015).

To address these concerns, the South African NDoH recently introduced their National Adherence Guidelines for Chronic Diseases including HIV, TB, and NCDs to enhance treatment adherence, working towards Vision 2030 of the National Development Plan (Republic of South Africa, 2012; NDoH, 2016). These guidelines aim to strengthen access to appropriate services in order to improve clinical outcomes, and for people with chronic diseases ensure linkage to care, retention in care, and support, to enhance their adherence to treatment (NDoH, 2016), with enhanced adherence improving outcomes (Ho et al., 2009; Corrao et al., 2011; Abegaz et al., 2017).

Overall, the aim is to introduce a minimum package of interventions to ultimately support linkage to care, adherence and retention in care, to improve future patient outcomes. This includes standardized education counseling on hypertension, diabetes, TB and HIV, including child and adolescent disclosure counseling. In addition, alternative repeat prescription collection strategy options (see section Access to Medicines), early tracing and retention in care as well as integrated management of chronic conditions involving multi-disciplinary groups. This will include patient adherence plans and pamphlets, adherence information, training files, standard operating procedures, fast track initiation counseling, and the setting of treatment goals (Toit, 2017).

There are ongoing programmes within hospitals in South Africa to instigate antimicrobial stewardship programmes (ASPs) to reduce AMR (Brink et al., 2016; SAASP, 2017), which is a growing problem worldwide (WHO, 2014, 2015; Hoffman and Outterson, 2015; Mendelson and Matsoso, 2015; NDoH, 2015a,b). Antimicrobial stewardship refers to coordinated interventions designed to improve and monitor the appropriate use of antibiotics by promoting the selection of the optimal antibiotic agent(s), dose, duration of therapy, and route of administration. The large burden of infectious diseases in South Africa has necessitated the following specific antimicrobial stewardship goals: optimizing therapy for individual patients, preventing overuse and misuse of antibiotics, and minimizing the development of resistance at patient and community health levels (NDoH, 2015a,b).

This increasingly includes utilizing existing resources of pharmacists, registered nurses and other healthcare programmes to co-ordinate anti-infective management programmes and subsequently improve patient outcomes (Schellack et al., 2016; Goff and Mendelson, 2017). Major shifts in policy toward combatting AMR within the South African healthcare environment culminated in the NDoH's publication of South Africa's Antimicrobial Resistance National Strategy Framework 2014-24, published in October 2014 at a Ministerial Antimicrobial Resistance Summit to retain the effectiveness of available antibiotics (NDoH, 2015a) This is a multidisciplinary, intersectoral strategy combining human health, animal health, and environmental health sectors, which is implemented through the MAC on AMR. One of the strategic objectives of the framework was to “promote appropriate use of antimicrobials in human and animal health” through ensuring access to safe, effective and affordable antimicrobials, institutionalizing ASPs across sectors, and addressing the use of antimicrobials in animal health and crop production. This Committee is currently developing a series of guidance documents regarding the governance structures necessary at each level of care, the monitoring of antimicrobial use and resistance at the healthcare level, and the appropriate use of antimicrobials at all healthcare levels, in human and animal health (NDoH, 2015a,b).

Parallel to this, and as part of the country's drive towards quality healthcare service delivery, specific antimicrobial stewardship, and infection prevention control norms and standards were finalized and published for public comment in the Government Gazette, with a view to becoming enforceable regulations in the future. The terms of reference of provincial AMR committees have been developed, and these committees are currently in the process of being established.

The need for pharmacist-led ASPs was demonstrated in a recent study with analysis of 47 private hospitals across South Africa revealing that close to one in every 15 prescriptions contained inappropriately prescribed antibiotics, requiring an intervention. The study highlighted the role pharmacists can play to improve future antibiotic use in South Africa as infectious disease-trained specialists are currently limited in number (NDoH, 2015a,b; Brink et al., 2016). Research is also being undertaken in public hospitals to assess the situation in this important sector (Schellack et al., 2017; Bester et al., in press).

Furthermore, the Committee is currently developing a national AMR and antibiotic use national surveillance dashboard, which includes private and public healthcare sector data. The South African Society of Clinical Pharmacy has also developed a guideline to outline the importance, role and purpose of pharmacists in ASPs within South African hospitals to improve the use of antimicrobials. This is in addition to other strategies as part of the South African government's national strategy initiative to reduce AMR (NDoH, 2015a,b).

It is also recognized that the role and functionality of PTCs needs to improve within the health system, at provincial, district, and institutional levels, in South Africa to enhance appropriate medication procurement and usage decisions to ensure sustainable financial practices that will improve patient care following the instigation of the National Drug Policy in 1996 (NDoH, 1996; Gray et al., 2015). In light of this, the National Policy for the Establishment and Functioning of Pharmaceutical and Therapeutics Committees in South Africa was published in 2015 (NDoH, 2015d). A guidance document with clearer directives on the functioning of the PTC is currently under development. PTC activities typically include dissemination of decisions from the NEMLC meetings as well as any formulary management changes at their respective healthcare institutions.

However, there are concerns with the level of reporting of adverse drug reactions (ADRs) and medication errors, as well as lack of evidence-based decision-making in formulary management (Suleman, 2010; Matlala et al., 2017a,b; Truter et al., 2017). This follows research highlighting the lack of reporting of ADRs within hospitals in South Africa, exacerbated by lack of knowledge of the processes involved (Matlala et al., 2017a; Terblanche et al., 2017a). This is perhaps not surprising with published research highlighting in South Africa that ADRs frequently develop whilst patients are in hospital (Mehta, 2011; Terblanche et al., 2017a). In addition, in a study conducted among four adult medical wards in South Africa, the authors estimated that ADRs contributed to the death of 2.9% of admitted patients (Mouton et al., 2015). The overall mortality rate was 18 per 100 admissions, with 16% of deaths ADR-related (Mouton et al., 2015). These factors have resulted in concerns regarding the current extent of pharmacovigilance activities in South Africa. However, recent studies among South African teaching and secondary hospitals have shown the benefit of pharmacists' interventions making it easier to detect adverse events, and to classify harm to a particular adverse event, to improve reporting rates and subsequent patient care (Müller et al., 2016; Terblanche et al., 2017b).

Previously, pharmacovigilance has been seen as a relatively new science in Africa (Ampadu et al., 2016). This has changed with an appreciable number of African countries now part of WHO Programmes for Drug Monitoring including South Africa (Ampadu et al., 2016). Pharmacovigilance (PV) activities in South Africa have been helped by the formation of a national PV Working Group within the Medicines Control Council (MCC) of South Africa dedicated to this (MCC, 2017), providing direction (MCC, 2012). There have also been regional initiatives to further improve PV and the reporting of ADRs (Gauteng, 2017).

However, despite these initiatives, most healthcare professionals in public sector hospitals in South Africa seem unaware of ADR reporting systems, with only a very limited number of professionals receiving training on ADR reporting, with the vast majority indicating the need for such training (Terblanche et al., 2017a). Following the recent introduction of a pharmacist-driven PV system within a public sector hospital in South Africa, the vast majority of healthcare professionals now support the system (97%), with 85% understanding the need for ADR-reporting. This is helped by 69% now knowing there are ADR forms available (up from 15.2%), with 73% now knowing to whom ADR reports should be submitted (up from 19%). Reasons for non-reporting of ADRs also decreased significantly (Terblanche et al., 2017b).

To further increase access to appropriate reporting channels, access to the national ADR reporting forms are now available on the EML Clinical Guide mobile application. Reports submitted on this application are received by the NDoH Pharmacovigilance Centre for Public Health Programmes and forwarded to the MCC. It is hoped this innovation will also increase ADR reporting as the use of smart phones continues to increase in South Africa.

A pharmacist's participation in the management of hospital in-patients on ARV treatment through the provision of pharmaceutical care has also proven to be beneficial for the identification, management and reporting of ADRs (Ally et al., 2015). This kind of research, and the implications for future activities to reduce the extent of ADRs, and their implications on patient morbidity, mortality and costs, will also be undertaken among public hospitals in South Africa to improve future patient care.