Posted 03 November 2014
The South African Health Review (SAHR) 2013/2014 was launched in Pretoria on 29 October 2014. Now an officially accredited peer-reviewed journal that chronicles the development of South Africa’s health system, the South African Health Review offers current, evidence-based insights into the status of integration of policy and implementation in a range of healthcare structures, protocols and processes.
One of the chapters addresses Health Policy and Legislation, authored by Andy Gray and Yousuf Vawda. The complete chapter can be accessed here. A highly pertinent part of this chapter is that addressing Medicines and Related Substances Act.
This is reproduced below.
Medicines and Related Substances Act
Although a draft of the proposed Medicines and Related Substances Amendment Bill was published for comment in March 2012, this Bill has not been issued in final form, nor does it appear to have been tabled in Parliament, despite being approved by the Cabinet on 18 September 2013.38,39 Without the passage of this enabling Bill, or the promulgation of the 2008 Amendment Act, the creation of the South African Health Products Regulatory Authority (SAHPRA) cannot proceed.40 The reasons for the delay of this Bill, which appears now to be somewhere between the tagging mechanism and the First Reading stage before referral to the National Assembly Portfolio Committee on Health, are unclear.
To some extent, it may merely be a casualty of the run-up to the 2014 election, but there remain concerns about the viability of the proposed regulatory structure. One of the key definitions in the proposed Bill is that of a “health product”, which is defined as “a medicine, Scheduled substance, medical device, IVD, cosmetic or foodstuff”. The 2008 Act had defined “IVD” as an “in vitro diagnostic medical device”, meaning “a medical device, whether used alone or in combination, intended by the manufacturer for the in-vitro examination of specimens derived from the human body solely or principally to provide information for diagnostic, monitoring or compatibility purposes”. The circular reference would indicate that the 2008 Act will also need to be promulgated. However, more importantly, the definition of a “health product” shows the breadth of the regulatory scope envisaged for the new regulatory authority.
The regulatory approach to complementary medicines has been highly contested for many years, not least since the publication of the 2002 notice by the Medicines Control Council (MCC), which was referred to by some as a “call-up” notice, with a much abbreviated requirement for information, and by others as merely an information-gathering exercise.41 In November 2013, the Minister finally published amendments to the General Regulations to the Medicines Act, which promised to provide much-needed clarity in this regard.42 The Regulations, which came into effect on the date of publication, defined complementary medicines (CMs) in relation to three elements, all of which would need to be met: “complementary medicine” means any substance or mixture of substances that (a) originates from plants, minerals or animals; (b) is used or intended to be used for, or manufactured or sold for use in assisting the innate healing power of a human being or animal to mitigate, modify, alleviate or prevent illness or the symptoms thereof or abnormal physical or mental state; and (c) is used in accordance with the practice of the professions regulated under the Allied Health Professions Act, 1982 (63 of 1982)”. At the same time, the Medicines Control Council published final guidelines on the assessment of complementary medicines in relation to quality, safety, and efficacy.43 Two additional draft guidelines were published for comment at the same time, dealing with the fees to be charged for complementary medicine applications and the use of the electronic Common Technical Document (eCTD) for such applications.44,45 Some weeks later, a rather dated document entitled “Roadmap for registration of complementary medicines” was also placed on the MCC’s website.46
One of the clearer statements in that document related to the status of the 2002 notice: “On 22 February 2002 the Council published a notice in Government Gazette No. 7282, R. 204 solely for the purpose of an audit of products already on or about to enter the market at that time, for a period of 6 months. The intention was that the audit should have been completed in respect of those products available on the market by 22 August 2002. Nevertheless, submissions dealing with the subject matter of the 2002 notice continue to be made to the Medicines Control Council”. Further, it made the intention clear: “The 2002 notice has led to much uncertainty amongst importers, manufacturers, wholesalers, retailers and consumers regarding the legal status of these products, as companies who submitted such applications were often under the misconception that these submissions were serving as applications for registration rather than simple notifications. Government Gazette Notice R. 870 of 15 November 2013 calls for the legislative control of all these complementary or alternative medicines”.
Importantly, the regulation of complementary medicines did not entail an amendment of the Act itself, but relied on the current provisions in sections 14 and 15, and the standard approach to assessing quality, safety and efficacy. In the same way that the specific requirements for data vary between new chemical entities (which are assessed on all three criteria) and generic medicines (which are only assessed on quality, with an additional requirement to show interchangeability), a specific set of criteria has been established for medicines that meet the definition of “complementary medicines”. Critically, these would be restricted to medicines “associated with those disciplines regulated by the Allied Health Professions Council of South Africa (AHPCSA). These are commonly known as Homeopathic medicines, Western Herbals, Traditional Chinese medicines, Ayurvedic medicines, Unani-Tibb and Aromatherapeutic medicines/oils”. Specific reference sources and lists of substances were prescribed for each complementary category. One of the pressing tasks will be to identify products that are on the market currently, which may have a registry number issued in terms of the 2002 audit, but do not fit the new definition of a CM, and should therefore either be registered as medicines or removed from the market.
A risk-based approach, differentiating between high-risk and low-risk health claims has been adopted. Examples of “high-risk” claims listed include “Treats/cures/manages any disease/disorder”, “Prevention of any disease or disorder”, “Reduction of risk of a disease/disorder”, “Aids/assists in the management of a named symptom/disease/disorder”, “Relief of symptoms of a named disease or disorder”, and “Treatment of proven vitamin or mineral deficiency diseases”. In order to justify such a claim, applicants would be required to submit clinical data, drawn from at least two of the following four sources: recognised Pharmacopoeiae, recognised monographs, three independent written histories of use in the classical or traditional medical literature, or citations from other in vivo or in vitro studies, case reports or other sources. Lower requirements have been stipulated for low-risk claims, defined as “General health enhancement without any reference to specific diseases or conditions”, “Health maintenance, including nutritional support”, or “Relief of minor symptoms (not related to a disease or disorder)”. This statement from the guideline is self-evident, but may prove difficult to apply: “The evaluation of high-level claims (i.e. for the use of medicines for serious illnesses) requires an assessment of the differential between the benefits of a medicine and the risks of its use.
There is no simple measure for this: the acceptable level of risk varies with the nature of the benefits, the risk from taking the medicine and the risks of untreated (and undiagnosed) diseases. Generally, the more serious and life threatening the untreated disease and the greater the benefit, the higher is the level of acceptable risk. The benefit-risk profile is also affected by the availability of accepted (proven) treatments, the risk profile of those accepted therapies, and the risks of foregoing treatment where such a medically acceptable option is available. A benefit-risk profile should be determined for every complementary medicine – even for so-called “minor conditions”.
However, regardless of the specific requirements in terms of safety and efficacy, all CMs will be subject to compliance with current Good Manufacturing Practice. Detailed guidance on the approach to assessing the quality of CMs is provided.
As with the implementation of the initial Act from 1967 onwards, this process will take years to implement. The new General Regulations therefore stipulate that all CMs that are as yet unregistered must include the following disclaimer on their labels: “This medicine has not been evaluated by the Medicines Control Council. This medicine is not intended to diagnose, treat, cure or prevent any disease”.
Unusually, the amended General Regulations also included a riskbased set of deadlines. Those related to labelling, package inserts and patient information leaflets would come into operation three months from the date of publication of the amendment. With specific reference to the CM category (the new Category D medicines), those which fell in the pharmacological classifications of antiviral agents, oral hypoglycaemics, cardiac medicines and cytostatic agents would be called up immediately for registration. Accordingly, any CM in such categories that was already on the market would need to have an application for registration submitted within six months from the date of publication of the Regulations. Any new CM in such pharmacological classifications that was brought to market after the same date would first need to be registered. Delayed application of the same rules was specified for other pharmacological categories: by 24 months for CMs in the pharmacological classification slimming preparations, male sex hormones, female sex hormones and androgen-oestrogen combinations claiming sexual stimulation and sexual dysfunction benefits; and by 30 months for any CMs claiming immune stimulation (or similar expressions), medicines acting on the muscular system, and vitamins claiming to be sport supplements and exceeding the upper limits for vitamins and minerals as published by the MCC. Finally, it was stated that the entire process, for all remaining pharmacological classifications, would be completed no later than December 2019. Although vitamins were mentioned in relation to sports supplements, they did not appear to meet the definition of complementary medicines. This view was further supported by the inclusion of new inscriptions for both vitamins and probiotics in amended Schedules published by the Minister in February 2014.47
Although this regulatory scheme does not deal with the very challenging issue of African Traditional Medicines, it would appear to provide the means to tackle the ever-expanding and out-ofcontrol CM market, using a risk-based approach that draws on the experience of a number of other regulators, notably the Australian Therapeutic Goods Authority. Whether the MCC inspectorate (or its successor in the form of SAHPRA) has the means, capacity and will to implement these Regulations remains to be seen. Three workshops were arranged in February 2014 to enable the regulator to explain the new guidelines to the CM industry.48
The existing provisions of the Act were nonetheless sufficient to declare an unregistered product claiming to be an effective anti-malarial (Nordman Artemesia Anti-malaria Capsules) as undesirable.49
In addition to the vexed issue of CMs, the amended General Regulations addressed a number of problems that had emerged since the last set was published in 2003. Some were simply typographical errors, such as tidying up the requirements for registers to be kept by all sellers of specified Schedule 5 substances. Others addressed areas of concern, such as the requirement that anyone entering or leaving the country could only do so with 30 days’ supply of medicines for personal use. This was replaced with a three-month quantity for those entering the country only. In addition, the control over clinical trials was extended to those involving animals.
Without much fanfare, an important concession was granted in relation to holders of dispensing licences in October 2013.50 Provided that the holders of such licences paid the annual fee, they would remain valid until suspended or revoked by the DirectorGeneral, instead of being renewable every three years. By contrast, licences to manufacture and to act as a wholesaler or distributor of medicines would remain valid for only five years.
The Medicines Act also includes the regulation of prices in the private sector. In January 2013, the Minister stipulated that single exit prices in the private sector could be increased by a maximum of 5.8%.51 On 1 February 2013, the Director-General issued final guidelines on the submission of pharmacoeconomic analyses in relation to medicines, but their application remains voluntary until further notice.52 It is unclear whether any such submissions have yet been submitted, or whether the Department has made any determinations on the basis of such submissions. The degree to which the medical schemes will accept or act upon such determinations has also been questioned.53 In September 2013, the Minister of Health issued a notice calling for submissions in relation to the single exit price increase for 2014, also providing a hint at the weighting to be applied in relation to local consumer price inflation and the exchange rates relative to the Euro and US dollar.54 One of the unintended consequences of the single exit price system has been the apparent ban on any donation programmes in the private sector. In that regard, an MCC notice of section 36 exclusions issued in June 2013 was significant.55 It exempted a particular product from the application of section 22G(3)(a) of the Act and General Regulation 6, but “solely for the sale at no cost to one A Vahed at the prescribed dose of his treating Physician”. This is a clumsy and time-consuming solution to the problem, requiring a unanimous recommendation from the MCC for reaching a decision. In May 2013, the Registrar used the same mechanism to extend the exemption of Schedule 0 medicines from the transparent pricing system, including the ban on bonusing, for a further three years.56 In January 2014, the Minister of Health stipulated that the maximum increase in the single exit price for 2014 would be 5.82%, and the Director-General published the requirements for applying for such an increase.57,58 The low maximal increase in the single exit price was immediately criticised as not taking ongoing exchange rate fluctuations into account, which elicited a response from the Department indicating that extraordinary increases in 2014 might be considered and that the formula for determining such increases might be reconsidered.59 However, allowing more than one increase in a single exit price cycle would require a change in the Regulations.
In September 2013, two sets of Schedules to the Medicines Act were issued by the Minister.60,61 The first of these was significant, as it listed substances in each of the schedules to be prescribed by various categories of emergency personnel, dental therapists and optometrists. These were the first such listings in the Schedules, allowing for the application of Section 22A of the Medicines and Related Substances Act, as had been in place since 2003. However, while other applications for similar listings were in progress, no movement had yet been made in relation to nurses, the most common non-medical prescribers in the health system. A draft guideline for such applications was published by the MCC in October 2013.62