Supplementary notes

  1. In 1963 the Snyman Commission was appointed to investigate the costs of medicines and related matters. The Commission’s report, which was presented 2 years later, recommended that medicines in South Africa should be controlled in terms of their purity, safety and therapeutic efficacy. The recommendations led to the drafting and promulgation of the Drugs Control Act, 1965 (Act 101 of 1965). This Act, which was aimed at controlling medicines for human use through the establishment of a Drugs Control Council, came into operation in 1966. The regulations to Act 101 were published in December, 1967. All medicines coming on to the South African market from 1966, and the introduction of the registration procedure in 1968, required registration. Those medicines on the market prior to 1968 were known as the "old medicines" category.

Brief details of some of the most important amendments to Act 101 follow.

Its provisions were wide-ranging. They included the following points.

It was at the time of the promulgation of this Amendment Act, at the beginning of 1998, that this review was undertaken.

In summary, drug regulation in South Africa was introduced in the mid-1960’s, in common with developments in many other countries at the time. Then followed a period of approximately 15 years, during which fairly regular amendments were made, on average every 2 years or so. Between 1981 and 1991, however, little appeared to change. It is possible that during this time inadequacies in the legislation were left to find their own level, and/or that procedures and systems within the regulatory authority were consolidated. Two noteworthy changes in 1991 were the removal of the disqualification for Council members to have an interest in the sale of medicines, and the abolition of the Medicines Control Appeal Board. The extensive amendments of 1997, the first after the election of a broad-based government in 1994, were aimed at implementing some of the aspects of the National Drug Policy, as mentioned in Section 3.2 below, and in removing some of the anomalies in earlier legislation. They were also directed at eliminating some negative practices and perverse incentives that had developed in the marketing and use of medicines over the years.

    Remuneration has never been the principal motive of these experts in working for or in the Council; the current remuneration of a Council member and the fee paid for the compilation of a report (R73 per hour) are very much less than what a similar expert might expect to receive if undertaking comparable work for a pharmaceutical company. Instead, one finds that (again, as in many other countries) these experts have been motivated by a sense of public duty, by scientific interest in the topic and by the educational value of participating in the work.

    The success of drug regulation and policy can be measured in various ways. Is there a backlog of ongoing work? Are acute matters dealt with sufficiently promptly? Are the standards of quality, safety, efficacy and truth which the public interest demands being met?

Ongoing work: The Review Team were provided by the Directorate: Medicines Administration with some data showing the periods within which new drug applications or other matters are dealt with, but the data lacked detail. From the data provided, however, it appears that the number of applications has increased substantially since 1992, and the duration of processing times has also increased. This was confirmed in submissions from the industry.

Where these have been introduced in other agencies, it appears that they have had a positive effect on improving efficiency without compromising the quality of decisions taken.

The Review Team identified some of the possible reasons for the variability in processing times. Some applications slip behind because a particular external assessor retains a file for an unreasonably long period, and the system has no reserve capacity to correct such a problem by transferring the work to another assessor. It can also happen that because of overburdening of the Council's agenda applications have to be delayed until a subsequent meeting. Analogous problems arise with applications for modification of a license, which are very numerous, and the handling of applications for generic products. Processing is often erratic because of shortage of capacity, competition from other activities and the strong pressure exerted by some applicants - sometimes directly on assessors - to secure priority. This last factor is compounded by one of the performance measures used to assess MCOs - files "finalised" (= approved) is used a criterion for performance appraisal, without considering the complexity of quality of either application or evaluation.

The Review Team identified a number of backlogs in the system. It was estimated that there is a backlog of between 400 and 800 current applications. There are also substantial backlogs in assessing older (pre-1965) drugs (possibly 4000 or more) and in entering data into the administrative system. As well, the process of entering registered products on the new database (based on the WHO/SEAMED software) is significantly behind schedule, due to lack of resources and the transfer of staff. It is important to note that the problems do not relate only to handling the existing workload; the capacity is lacking to face the current and apparently continuing increase in applications of all types, which seems likely to increase delays still further.

Acute problems: Because capacity is not sufficient even for routine work, there is in fact no reserve to handle an acute problem, e.g. a drug safety issue or a request for advice from the Minister of Health. Where such a matter has to be dealt with by the Council for either medical or political reasons, other work simply gets delayed. It seems likely that a Council Chairman may have difficulty in setting the right priorities in this respect; in other organizations of similar type, a Secretariat may be better placed to guide the Chair and the Committee in such situations, but this will still not solve the fundamental capacity problem. This is therefore both a procedural problem and one of capacity.

Maintenance of standards: In so far as drugs are dealt with and the necessary technical reports are compiled and are considered in the Council, the standards of assessment attained have at times during the last three decades and at their best approached or attained those of similar bodies in, for example, Australia, The Netherlands and Scandinavia. One cannot conclude that this relative success has been maintained in recent years. Some of the reasons have been noted above: a constantly overstretched organization cannot be expected to work to consistently high standards. Other particular reasons for variable or slipping standards seem to include:

The isolation of South Africa prior to 1994 appears to have contributed to the development of somewhat idiosyncratic approaches to standards for registration of products. A particular example is the development of standards required for establishing bioequivalence of products, where South Africa has relied very heavily on the use of dissolution data rather than formal bioavailability studies. This is internationally acknowledged to be a difficult and contentious area of drug regulation but equally, international standards have been developed; to date South Africa has not adopted them.

The Team cannot draw conclusions as to whether pharmaceutical assessments are adversely affected by the presence of industrial experts in the Committee concerned; they appear to be highly expert, and the Team's concern in this connection relates to a matter of principle rather than of quality - it is hardly desirable that an expert attached to a firm be involved in the assessment of a file submitted by his own company or by a competitor. Recommendations on this matter are made in Section 5.9.

Taken as a whole, then, the South African drug regulatory system seems to have been capable in the past of carrying out its work and achieving at times the high standards which public health demands; however, significant delays and faults now occur because its capacity is either marginally sufficient or insufficient, and because procedures are not optimal.

    In particular, the Review Team has considered it inadvisable to consider in detail the recent and ongoing controversy, relating to the drug Virodene. This case and other crises illustrate the lack of clarity in the present system.

    A common concern raised in submissions from pharmaceutical manufacturers, external groups and Committees of the Council was the difficulty in day-to-day communication with the Directorate. A simple solution to this would be the appointment of a dedicated liaison officer as the designated contact person - this would also solve the problem of individual MCOs being "pursued" about individual applications by industry. Such a person might also handle enquiries from the general public and media.

    A particularly regrettable aspect of the present situation is that the regulatory body only comes into the professional and public view when conflicts arise, e.g. as recently with respect to Virodene. By ensuring development of ongoing communication, the regulatory agency can put its long-term performance in the public interest at centre-stage, thus ensuring that incidental controversies are put into perspective.

    Characteristic of the inadequacy of current data handling is the unrealistic amount of paper provided for Council and Committee meetings, some 20-30 times greater than that customary for Council members in other countries and far in excess of what one can realistically expect members to study in advance. The courier or mailing costs of distributing massive documentation to numerous addresses are unrealistically high.

Partly as a result of inappropriate agenda preparation and partly as a result of the confusion of roles and responsibilities, a "between meetings" decision making process has evolved. This is common in many MRAs and is usually carried out by an Executive of the main decision-making body. In order for it to function effectively, it requires careful standardisation of the process, with appropriate communication of decisions taken. In the South African system, although there is a formal Executive of the MCC, it does not appear to meet regularly; decisions taken between meetings seem to be taken by the Secretariat with input from the Chairman of the MCC, plus other members of Council as needed, and there appears to be no standard process for communicating these decisions to the MCC as a whole.

Overall the processes used in the South African regulatory system appear to be complex, administratively inefficient and involve many committees, with what appear to be numerous "loops" around the process without clear purpose or need.

    The question of how members of Council Committees are appointed is raised in the Terms of Reference for the Review. In the past, it seems that Committees were able to recruit new members as they saw fit, and this was carried out by the Chairs of each Committee, based on personal knowledge of the skills and expertise of the person concerned. This approach resulted in a fairly limited number of groups being involved, concentrated at a small number of tertiary institutions. Since the current government came to power, a more formal process for appointing Committee members has been introduced, requiring a Committee of Council (the Nominations Committee) to review possible appointees, to ensure that due consideration of the need for transformation is included in the appointments. This has had its difficulties; there has been perceived conflict between the need to appoint members with appropriate expertise and the need to ensure that previously under-represented population groups are included in the Committees.

    Such rules are sufficiently flexible to enable committee members and experts to engage in industry-support projects so that they remain active in medicines research, but require them to refrain from any participation in debates or assessments involving the drugs or firms with which they are working. Long-term consultancy appointments to pharmaceutical companies are regarded as incompatible with work for the medicines control authority. Especially strict rules usually apply to the Chairman of an authority or committee, e.g. prohibiting acceptance of industrial support for his university unit.

    The Team has identified two possible reasons for the increase in workload. One is that South Africa is "catching up " with other countries in terms of the evaluation of NCEs and major new uses of registered products; the other is the large volume of applications for generic imported products.

    . One factor affecting the remuneration of clinicians has been the introduction of limited private practice (LPP) for clinical academic staff. This was introduced 5 years ago as an alternative to the substantial salary increases that were under negotiation at the time. It allows academic staff in the medical schools the opportunity to utilise up to 20% of their normal working time to treat private patients. In some instances, structures and mechanisms were developed within a medical school so that time allocated to this purpose and the disbursement of the funds were under some degree of supervision (so-called internal LPP). Where this approach could not be, or was not, implemented, academic staff practised from private rooms and in some cases set up their own private practices (so-called external LPP). The effect of this situation on their teaching and service responsibilities was variable, but in some cases resulted in staff not being available in the afternoons. Income became an issue of concern, with the possible result that commitment to lower-paid activities, such as work associated with the MCC, lessened.

    . Such pressures on university finance are not unique to South Africa: they are worldwide, as universities increasingly find themselves obliged to restrict themselves to their core teaching and research activities, and to identify remunerative activities to swell their funds (including, for example, work for the pharmaceutical industry).

    . South Africa has an unusually wide range of medicines of this type to deal with, in view of its multiracial composition; some 25000 products appear to exist. The situation has not yet been comprehensively tackled and several contacts describe the market as "chaotic". A proposal to deal with the situation was drafted for the MCC in 1997 but up to February 1998 it had not been discussed. Representations from manufacturers of products in this case reflect a marked division of opinion as to whether they would like to see them registered under medicines legislation, handled under a separate law, or rendered exempt from regulation.

    . Another result of the "closed shop" approach has been that new Committee members appointed from outside the traditional groups generally have very little knowledge of drug regulatory processes. There has been no systematic attempt made to provide them with orientation to the MCC or its Committees, and as a result, they cannot and do not function adequately as members of the MCC for several meetings. This is clearly a waste of valuable time and expertise and could be resolved very easily by introductory workshops and documents.

New MCOs in the Directorate have faced similar problems. Although there is some orientation and basic training provided, it is not adequate given the complexity of the roles and responsibilities that MCOs undertake. An example of effective training however is the programme currently running in the Medicines Control Sub-Directorate - Inspectors spend a week every quarter in training, with appropriate practical exercises and visits being a key part of this effort.

    It would appear that in the past international contacts and travel have been based on a few people attending high profile meetings (such as the various ICH meetings) that have not necessarily been of the most relevance to the needs of South Africa. As discussed in more detail below and in the main text, there is clearly a need to maintain and develop international contacts in some areas (such as in the exchange of evaluation reports, and inspection reports via the PIC group) but these should be in the context of an overall assessment of the needs of the MRA. One possibility that might be explored for the future MRA is exchange of staff with other agencies, as way of acquiring appropriate expertise.

    International and regional initiatives are still based entirely on the existence of competent national agencies and their ability to contribute to joint efforts; this is for example the case in the European Community, where the centralized agency in London merely complements the work of national agencies and handles only a very small proportion of the work undertaken to assess specific drugs. South Africa can and must render its own system much more efficient by benefiting from foreign and international initiatives but it is faced with many purely national issues, including the products of national producers and importers, the massive challenge of complementary and African traditional drugs, national patterns of use of medicines and widespread conduct of clinical trials involving its nationals.

    A good example is the successful replacement of the Central Medical Stores of Uganda by the National Medical Stores in 1993. A new body is entitled to decide selectively which of the elements in the earlier body (procedures, members of staff, advisers, assets) it wishes to adopt. Other parties are more inclined to approach a new body without prejudices dating from past experience.

    In recent years, for example, the United Kingdom, Sweden and The Netherlands have made their agencies autonomous. They prove readily capable of covering their costs, but if their entire budget is paid by industrial applicants industry acquires too dominant a position, sensing that it is in a position to influence policies and standards. While an agency must be fair to applicants, its essential duty is solely to the community and to public health.

    It is true that even the existing/former MCC had a purely technical task defined by law, but a series of events show that it has sought to assume in addition a role in the determination of medicines policy. Naturally, any agency may in the light of its experience make representations on policy issues to the Minister concerned, and will sometimes be asked for its opinions on these matters, but this does not alter the fundamental division of responsibility.

    Much work can for example be eliminated by setting uniform texts for the data sheets/package inserts for closely similar groups of drugs (beta-blockers, thiazide diuretics, most benzodiazepines). Similarly, the requirement of "efficacy" as set in the law will require special interpretation where one is dealing with vitamin supplements (which are not pharmacologically active in the normal sense) or fixed combination drugs (where it is necessary to look to the effect of each individual component as well as to that of the total mixture). Guidelines on such matters prove as helpful to applicants as they do to the agency itself. Some guidelines have been created by the current MCC and others can be based on texts used abroad, adapting them needed to South African requirements.

    In order to conform formally to the requirements of the existing Act 101, so long as this has not been amended, the Board may initially need to bear the title of Medicines Control Council.

    The Review Team sees this purely as a review procedure which can be applied once only to any particular decision. Once the decision has been reaffirmed or revised, it will not be questioned again by the Board.

  1. Such tasks can include approval of minor modifications to packaging or texts, or assessment of new data submitted to meet minor objections to registration. A strengthened Secretariat might later prove capable of assessing applications for generic products or parallel imports (see Figure 1, main text.)

    2. It is clear that communication must be limited to technical matters, avoiding statements on policy and ensuring that there is no breach of confidence. An underlying aim of this communication with the exterior must be to restore and develop confidence in the regulatory process by demonstrating that it is fully serving the public interest. One means of promoting confidence will be regular communication with the professions, e.g. by means of an information bulletin, e.g. as part of a government drug information service (see Section 6.3.); some excellent foreign bulletins issued by national agencies, e.g. as in Sweden and the United Kingdom, provide models.

    In order to conform formally to the requirements of Act 101, it may be necessary that this position should initially bear the title of Registrar until provision is made for the title to be changed.

    Bearing in mind that this group will in essence take decisions on all matters relating to scientific medicines it needs to have sufficient capacity in the three main disciplines (pharmaceutical, pharmacological/ toxicological, clinical) and certain others (statistics, bioequivalence). A total committee of some 12 persons, meeting every 6 weeks is likely to prove sufficient, although more frequent meetings may be necessary in the initial stages.

Technical support will be provided (a) out of house by clinical and pharmaceutical committees/assessors attached to universities as at present (providing peer-reviewed assessment reports on applications) and (b) in-house by the Technical Support Group within the Secretariat (undertaking pre-screening of applications as well as follow-up work after the Committee has considered the application, e.g. supplementary data or modification of package inserts).

The Expert Technical Committee will designate these external groups and assessors and provide them with guidelines for assessment and the compilation and peer review of reports, including time scales within which the work should be completed. External assessments will primarily be required for clinical and pharmaceutical data; toxicological and pharmacological data can generally be reviewed by the clinical assessors but in the case of new chemical entities not previously approved by any reputable foreign agency it will be wise to provide for separate expert assessment by one or more pharmacological/ toxicological/ teratological reviewers, and such reviewers should be identified by the Committee.

For new medicines based on well-established components, applicants will be entitled to submit bibliographic evidence of efficacy and safety rather than new and original scientific work.

For new generic products the most essential component in assessment will be their interchangeability with existing products. Although the Committee will have a member specialized in therapeutic equivalence it would be advisable to relieve the burden upon him by identifying at least two external assessors capable of making evaluations in this field, which the Committee member concerned can then review. As pointed out in an earlier note, much of this task might later be handled by a technically strengthened Secretariat.

  1. To take decisions on non-orthodox medicines belonging to a large number of different schools and philosophies, the group will have a very varied composition, perhaps with two representatives each from major areas such as homeopathy, herbal products, African traditional medicine, non-African traditional medicine and food supplements. Experts from other schools should be invited ad hoc to participate according to the business to be transacted.

Technical support will be provided (a) out of house by committees/assessors attached to the various schools (providing peer-reviewed assessment reports on applications) and (b) in-house by a Technical Support Group within the Secretariat (undertaking pre-screening of applications as well as follow-up work after the Committee has considered the application, e.g. supplementary data or modification of package inserts).

  1. Like ETC1, ETC2 will compile guidelines for external assessment to ensure that external reports meet their purpose, are appropriately presented and are peer reviewed before submission to the Committee.

Just as ETC1 in dealing with scientific medicines can assess certain familiar drugs on the basis of bibliographic data (standard textbooks) rather than requiring original investigations, so many complementary and traditional medicines can and should be accepted by virtue of their familiarity without full assessment. This is particularly important in view of the fact that many components are common to a large number of complementary products. The most efficient approach will be the establishment of a list of those components considered to be acceptable in traditional or complementary remedies and the doses or concentrations in which they are generally accepted to be safe. The list can be established by the Technical Committee concerned, subject to approval by the Board. Until such a list has been established for South Africa, it is suggested that the list accepted in Australia be employed. This and analogous approaches in other countries will be of great value in establishing the definitive list for South Africa.

    Such guidelines have been issued by other agencies and can form a starting point for developing a document appropriate for South Africa. As a rule claims should relate to symptoms rather than diseases; no reference should be made to resistant conditions, major infectious diseases, asthma, cancer or epilepsy.
    Appropriate manufacturing standards will also need to be established. Conventional GMP standards may be appropriate for some products in this area, but may not  be appropriate for all.

    The procedure needs to be restrictively defined. A new drug which according to the literature bears much promise for the treatment of an epidemic or hitherto untreatable condition is likely to qualify; a variant on an existing class of drugs, claimed by its originator to possess certain advantages as regards the cost/efficacy or efficacy/risk ratio is not. Various foreign models for fast-tracking procedures already exist.

    A new and truly promising drug for AIDS, with which little clinical experience has been gained, might for example be released in this manner for a specified period, one condition being the close involvement of experts designated by the Authority in its further clinical study, so that the release can be either extended or rescinded as soon as further evidence justifies this step.

    Examples would be (i) texts setting out the duties of applicants and registration holders. These are defined in much more detail in some other national texts than in South African practice. Typical is the need for a registration holder to notify the agency within a short and precisely defined period of time if his product experiences new problems or if foreign regulatory action is taken against it. (ii) The Notes for Guidance of Applicants relating to particular therapeutic classes of drugs as issued by the European Community. (iii) Bioequivalence standards issued by the United States FDA, or by WHO. (iv) Lists of acceptable components and claims for complementary drugs as issued by various regulatory authorities, as in Australia. (v) Rules relating to bibliographically documented applications for well-recognized drugs, as issued by the European Community (Directive 65/65 Section 4.8.(a)(ii) with modifications). Naturally, existing standards issued by the previous MCC in South Africa can also be adopted, if necessary after amendment, by the new Medicines Regulatory Authority.

An additional consideration is the format of applications. The current format is based on the dossiers accepted by the European Union countries, supplemented by a number of Annexes specific to South Africa. The Review Team has noted comments that some Annexes require much duplication of information, and whilst not having a strong view on this matter, suggests that the question of the optimal format for applications for the registration of medicines should be reconsidered by the new Board of the MRA in due course, particularly in the light of appropriate use of information technology. Wherever possible and appropriate, international standards for document presentation should be considered.

    . This confidentiality provision is deliberately formulated to reflect the situation internationally as of 1998. Many older laws in fact contained similar provisions, but in the course of the years they were often broadly interpreted so that some agencies regarded the entire contents of an application, and sometimes even the fact that it had been lodged, as confidential. With the development of Freedom of Information concepts, and demonstration of the risks resulting from concealment of toxicity data or adverse reaction reports, it has been widely acknowledged that the only valid commercial secrets relate to the mode of preparation of a drug, especially since these are unlikely to enjoy patent protection.

    For both purposes, good and well-tested foreign models exist. Oaths of secrecy which are normal in the Civil Service may need to be supplemented by more specific commitments relating to this field.

    A major agency may be considered at the present day to have a duty to contribute something to the development of regulatory standards at the regional and global level, thus relieving the burden which regulation imposes on countries at a lower level of development. This is one aspect of South Africa's participation in SEAMRAC. At the same time, links with other experienced agencies and with certain international bodies often render it possible to acquire foreign data and methodologies at little or no cost. Specific links with experienced agencies in Australia, Canada, the USA and northern Europe can result in mutual assistance both on matters of principle and issues involving particular drugs; written agreements and/or personal contacts can prove helpful. Exchange of assessment reports may be agreed with specific foreign agencies or through a multilateral agreement such as PER, provided this has been shown to be working effectively. In all these matters, mutual trust, often established on a personal basis by a leading member of the control agency itself, is at least as important as any official approach and sometimes much more effective.

    The Inspectorate, though part of the Directorate/Secretariat complex, already has a fairly distinct identity and task. Its 12 members, divided over four "business units" are responsible for:

There are also some related tasks, notably handling complaints about the sale of unregistered drugs, handled incidentally and as time permits. One task which is likely to grow is the control of drug advertising, which is to be the subject of a national ethical code.

The major task of inspection of factories is entirely separate from the Inspectorate of Pharmacies, which is maintained by the Pharmacy Council and does not fall under the Department of Health. Suspension of manufacturing licences, hitherto a task for the Pharmacy Council, moves under the newest legislation to the Inspectorate. Inspections are carried out both in South Africa and at certain foreign manufacturing plants exporting to South Africa. Application has now, after a remarkable delay, been made for membership of the Pharmaceutical Inspection Convention, which will render it possible to obtain and rely on inspection reports by member countries; this may be expected to eliminate the need for some, but not all, foreign inspections. India, for example, is not a P.I.C. member and is widely recognized to have an entirely inadequate national inspectorate; it exports heavily to South Africa and many Indian manufacturing plants are of poor standard; until some alternative arrangement can be found the public health interest will require that South African inspectors examine certain plants there. Where foreign inspections are necessary, it is customary for the firm to be required to pay the expenses involved as part of the overall fee.

Within South Africa, inspection of factories is well organized on the basis of a three-monthly cycle, involving both the inspectors based in Pretoria and others in the regions. The standard of the inspectors appears to us to be high, and the group is well managed, well trained and motivated. Any future modifications might relate to the provision of some legal capacity to handle law enforcement, the development of a summary procedure to deal promptly with advertising offences (where formal prosecution may take two years) and better integration of regional inspectors, who can easily suffer a degree of isolation.

One of the Terms of Reference of the Review Team was to consider whether pharmacy qualifications should continue to be mandatory for appointment as an Inspector. The Review Team does not have strong views on this matter; in some areas, industrial chemistry may well be as useful a qualification. The key issue, as has been noted previously, is the provision of adequate training to any person appointed as an inspector irrespective of previous qualifications or experience.

    It may be noted that the need to develop an overall policy with respect to drug information and rational use of drugs was expressed in the National Drug Policy document of 1996.

    This approach is not popular with companies, but it proves highly effective. There is much experience with it in the Netherlands, where it has become the norm.

    Much internationally acquired know-how is usefully brought together in:-
    Dukes M.N.G. (Ed.) (1993): Drug Utilization Studies. Second Edition. WHO Regional Office for Europe, Copenhagen.

    . Although some countries today maintain no more than a notification system for clinical drug trials, in the belief that little or no risk to public health is involved, there is in South Africa good reason to maintain the current system of some central assessment and registration of trials. There is a detectable belief in the multinational pharmaceutical industry that it is simple and cheap to conduct drug studies in African countries which might raise objections elsewhere; the relatively high academic standards of South Africa make it doubly attractive to set up investigations in this country. Both ethical and scientific safeguards are therefore necessary in the public interest.

    The Review Team noted that certain provisions concerning research on human subjects and national and local ethical appraisal are included in the provisional draft of the new National Health Bill, drawn up in December 1997.

    An argument for continuing to accord responsibility for trials approval to an MCO in the MCC secretariat is that the clinical pharmacologist in question is close to the drug approval process, and that the MCC is constantly evaluating the outcome of trials submitted to support new drug applications. On the other hand, approval of a trial protocol can never provide a guarantee that if it is conducted as proposed it will meet the standard required for drug approval.

An argument for transferring all responsibility to the Medical Research Council is that this would provide an opportunity to apply consistent ethical and scientific standards nationwide for the conduct of clinical drug trials. On the one hand, the scientific assessment could be conducted by the present Clinical Pharmacologist who would be transferred financially to the MRC but could remain located in Pretoria to ensure continued contact with the MCC. In parallel with this, the MRC could seek to develop closer contacts with institutional Ethics Committees throughout the country in order to promote the development of more uniform standards for drug trials.

An important consideration in deciding the optimal approach however will be the amount of pharmaceutical industry support received by the MRC. As it receives significant funds from the private sector, any potential conflicts of interest will need to be carefully assessed.

  1. Salient elements in this could be:

  2. See for example the WHO handbook:-

    3. Drugs and Money (6th Edition 1991; 7th Edition in press); WHO Regional Office for Europe, Copenhagen, Denmark.

    . The decision to establish a control system for medical devices and materials was taken in or about 1995. For this purpose a single pharmacist was transferred to the Medicines Directorate as the first step in creating a staff of seven persons. In fact no support staff has been provided and the pharmacist concerned only has some support from a small working group, which includes some industrial experts. The group has, among other things, recommended that the European Community's regulations of 1993 be adopted.

    . The Review Team recognizes that this approach represents a fundamental change of policy, since the intention to regulate medical devices has been an element of policy since Act 101 was passed in 1965.

    . There are many valid and well-tested models for medicines legislation; that based on the Directives of the European Community, as enacted since 1965, deserves serious consideration.

    . Low fees and high quality reviews appear to have been an incentive for industry to "try out" new applications in South Africa. If the application was approved, they had a new product on the market ; if not, they were given valuable advice about deficiencies in the dossier that could then be rectified before submitting it to another MRA - for virtually no cost. Therefore there have been a number of premature applications to be processed, contributing to overloading the system. Low fees have also had the potential to encourage applications from small companies with inadequate standards, again leading to increased workload for the system in processing them.

    . Draft Terms of Reference for financial analysis.
    To determine:-

  1. The current Committees of the Council will need to be reviewed, and their functions gradually transferred to evaluation groups. It may be of value to consider transferring some of the current members of the various committees to a multidisciplinary group specifically constituted to assist in clearing the backlog of applications. Members of some Committees (e.g. the Complementary Medicines Committee) might be expected to take on key roles in similar areas in the new MRA. Other committee members might take on the task of developing evaluation groups in tertiary institutions.

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