Regulatory authorities allocate resources to evaluate the registration of pharmaceuticals to ensure the health and well-being of patients through assessing the efficacy, safety, and quality of new, re-formulated, and multiple-sourced medicines [1]. Similarly, manufacturers have a vested interest in registering and selling medicines within the shortest time. The latter is because revenue generation to cover manufacturing, distribution, and research and development costs are only recouped through subsequent sales [2–5]. In most settings, registration of medicines and marketing authorisation approval is a prerequisite imposed by regulatory authorities on pharmaceutical manufacturers intending to market and supply medicines for human use to the public in a country [3].
In South Africa, medicines are registered by the South African Health Products Regulatory Authority (SAHPRA) in terms of Section 15 of the Medicines and Related Substances Act 101 of 1965 (Medicines Act) [1, 5]. After registration, manufacturers are required, in terms of Section 22G of the Medicines Act, to enlist the Single Exit Price (SEP) of a registered medicine at the National Department of Health (NDoH) before such a medicine can be sold in the private sector [6, 7]. Schedule 0, e.g., paracetamol in small quantities, and veterinary medicines, e.g., florfenicol injection, are excluded from this price listing requirement. Medicines registered for human use and subsequently supplied to Government facilities for use in the public sector follow a different tender process based on the South African Essential Medicines List [8]. It is common for medicines to reach the market and be sold in the private sector, under certain conditions, without SAHPRA registration [9, 10]. This is allowed in Section 21 of the Medicines Act, which provides access to medicines on a named patient basis over a specified period [9, 11]. Sometimes these medicines eventually become registered. Generally, it takes no more than thirty working days for the NDoH to process a submission intended for listing the SEP [7]. Immediately after enlisting the SEP, nothing prevents the manufacturer from selling the medicine to the general public, subject to any co-payment if not currently listed within private insurance scheme formularies; alternatively, patients do not have private insurance. However, despite this allowance, delays in patient access to medicines are observed the same way as in other countries [12].
The reasons for the lack of immediate patient access to medicines after registration include the on-selling of the dossier of the registered medicine to another manufacturer, delays in approval of post-registration amendments to registration dossiers [3], and price erosion [13]. Price erosion occurs when the pharmaceutical company is forced to reduce the price of medicines below the price that was envisaged before the registration [14]. This is mainly applicable to multiple sourced (generic) medicines, where companies can compete on price to be listed in the formularies of health insurance schemes or government databases. The latter depends on whether the company is identified as the preferred supplier after going through the government tender or negotiations with insurance companies, including the medical aid schemes.
The implications of market delay factors are that once the medicine has been granted market access, allocated a SEP, and declared ready for sale, the manufacturer might decide to terminate its plans to market the medicine to avoid revenue losses [3].
Additional access delay factors also involve medical insurance schemes. Medical insurance schemes either do not or only partly reimburse certain medicines, creating access problems for specific segments of the population [7, 12]. This results in patients being exposed to out-of-pocket co-payments for the shortfall amount required in order to access partially reimbursed medicines. Further, this partial reimbursement of medicines by medical insurance schemes can lead to limited access to registered medicines, particularly among members who cannot afford the full co-payment [2, 15].
The time lag taken to sell a medicine after registration is referred to as Time To Market (TTM) [12]. According to the European Federation of Pharmaceutical Industries and Associations (EFPIA), the “Patient W.A.I.T.” (Patients Waiting to Access Innovative Therapies) indicator provides a benchmark of the rate of availability and waiting times for new medicines [12]. Generally, the Patients W.A.I.T. indicator accounts for medicine access delays, some of which are due to the regulatory agency responsible for medicines registration or the pharmaceutical manufacturer [12].
In Europe, patient access to new medicines is highly varied. The average delay between market authorisation and patient access can vary by a factor greater than seven-fold, which means on a ratio scale, it can take one country 100 days for patients to access medicines after marketing authorisation has been granted relative to another country which may take over 700 days [12]. Across Europe and even within a country, significant variations exist in the speed of patient access to different medicines. In Northern and Western Europe, it can take up to 100 to 200 days for patients to access medicines after marketing authorisation is granted, whereas it takes between 600 to 1000 days in Southern and Eastern European countries [12]. The total time to patient access in Canada after regulatory approval and market authorisation continues to increase [16]. In 2019, the average market access delay timelines were taken up by Health Technology Assessments (HTA) and pan-Canadian Pharmaceutical Alliance (pCPA) negotiation processes, which contributed 236 and 273 days, respectively [16]. In Bulgaria, marketing delay periods currently exceed 365 days despite efforts to reduce them [17].
In Africa, Southern African Development Community (SADC) countries are reported to experience delays in patient access to medicines [3]. However, the extent of this delay is not yet quantified.
Regulatory authorities grapple with challenges in acquiring and retaining scarce and costly resources necessary to ensure expeditious registration of medicines, a regulatory process that leads to the granting of market authorisation of medicine [1, 3]. The authorities should ensure that these resources are not misused and that the desired outcomes, which serve the broader health interests of the population, are achieved and that consumers gain from the outputs of the work of regulatory agencies [5, 18]. Consequently, given the resources required by regulatory agencies to undertake their evaluations and typically more tasks than available personnel, it is reasonable to expect all registered medicines to be made available for sale and supplied to patients in the shortest possible time post-registration. However, the ultimate availability of new medicines will depend on various factors. This includes potential reimbursement by health authorities or health insurance companies based on their proposed price, envisaged value, and likely budget impact [19–20]. This is because there is increasing concern regarding the value and budgetary impact of new high-priced oncology medicines or those to treat orphan diseases, which account for most new medicines being researched [20–23].
Consequently, given limited information currently available in South Africa, we sought to determine the number and nature of registered medicines that are available in the private market in South Africa after-market authorisation is granted by the regulatory agency SAHPRA. This is because the selection of medicines procured in the public sector in South Africa is principally pro-generic, i.e., once available as lower cost multiple-sourced medicines, precludes the listing of many new premium-priced medicines, especially those with marginal health gains [8, 24]. This includes medicines such as long-acting insulin analogues until there are appreciable price reductions through bio-similars [22]. The study further aimed to establish the time it takes to start dispensing these medicines in the private sector after they have been registered. We also sought to explore the possible relationship between the types of registered medicines and those dispensed, including new patented medicines, new formulations, or minor changes in the molecule to extend the patent life, such as esomeprazole versus omeprazole referred to as 'evergreening'. We believe this is relevant because South Africa is in the process of implementing Universal Healthcare Coverage (UHC) policies, which seek to improve access to equitable healthcare and reduce the current differences in care delivery between the public and private sectors [25]. This is in line with one of the Sustainable Development Goals, 3, adopted by the United Nations [26]. However, the work performed by regulatory agencies in South Africa must be targeted to help ensure that the actual healthcare needs of the country’s population are met within the limited and scarce resources currently allocated to regulatory agencies in South Africa. As a result, resources should be prioritised where possible to assess the medicines that help address the current burden of disease rather than directed towards assessing medicines that are never launched. We are not sure this is currently the case, with applications for generics seeming to have a higher priority given pressures to procure and prescribe multiple sourced medicines, certainly in the public sector [27]. This is a concern if such activities lead to appreciable delays in patients accessing new originator medicines that can improve their health within acceptable costs. At the same time, preference is given to licensing multiple generic medicines, especially if a number of these are never launched with prices reduced due to increasing competitors.
Given this, the research questions are: Firstly, is there a relationship between registered and dispensed medicines and their Anatomical Therapeutic Chemical (ATC) classifications, which can identify the likely disease area for treatment? Secondly, what is the time typically taken to dispense medicines post registration at SAHPRA? Lastly, what proportion of multiple-sourced and originator medicines were registered in South Africa between 2014–2019? The findings can be used to suggest future priorities at SAHPRA to improve their efficiency and reduce time spent on appraising medicines that never reach the market. As a result, it helps positively impact the public health of patients in South Africa and the broader.