These articles  are by Health-e News Service and were  first published in What’s New Doc and on the Health24 website.

Nathan Geffen, Treatment Action Campaign treasurer, said that since the 1998 purge of MCC chairperson Peter Folb, registrar Johan Schlebusch and his deputy Christel Bruckner the quality of the MCC’€™s work has declined dramatically.

‘€œThere is a huge backlog of medicines that need to be registered and there is no clear results following the recommendations by Precious Matsoso’€™s task team,’€ said Geffen. Geffen was referring to a technical task team set up last year by then health minister Barbara Hogan to investigate National Drug Policy.

Geffen authored  Debunking Denialism, which among others chronicles how the MCC’€™s poor functioning has opened the floodgates for all kinds of quack remedies and questionable drugs.

‘€œThe MCC is an important institution, but it does not have the resources to do its work, it needs more money and people,’€ said Geffen.

MCC registrar Mandisa Hela initially agreed to answer a list of questions and to be interviewed, however, she later failed to return several calls and messages to her cellphone, her assistant in Pretoria and her e-mail. MCC chairperson Peter Eagles also failed to respond to the questions.

A senior source in the health department said the questions posed by What’€™s Up Doc were ‘€œspot on’€ and cut to the core of many of the challenges facing the MCC. But those who spoke to What’€™s Up Doc on condition of anonymity also agreed that Hela was working tirelessly to improve the situation at the MCC and that she had made great strides.

However, there was also agreement that many challenges still remained. Several sources spoke of a time when the corridors in the MCC’€™s second floor offices in the Hallmark building in Pretoria were clogged with overflowing cardboard boxes containing thousands of applications for registration, many of them for so-called complementary medicines. One source remarked to Geffen that there were about 20 000 alternative medicine applications sitting with the MCC unprocessed and with no plan to process them.

Some of this mess has now been cleared and order has been restored on the surface. Insiders said the new sense of urgency was also due to the involvement of Hogan’€™s former special advisor Dr Nicholas Crisp, who is now overseeing the establishment of a new Medicines Regulatory Authority, in line with the changes to the Medicines Act.

What’€™s New Doc contacted several drug companies and offered them an opportunity to comment on the functioning of the MCC. Aspen was the only company who agreed to the respond. All the others either failed to respond or declined to do so.

Stavros Nicolaou, Senior Executive Aspen Pharmacare said ‘€œthe Department of Health has commenced a process aimed at clearing the Medicines Control Council backlog and improving approval timelines.  Whilst these are early days, initial progress with the process is encouraging and we look forward to completion of the process.’€

Val Beaumont, Executive Director of Innovative Medicines SA said they were comfortable that South Africans were being protected from sub-standard medicines. ‘€œWe are comfortable that scheduled medicines in South Africa are being checked for safety and that standards set by the MCC are world-class,’€ she said.

Beaumont said there was a problem with the speed at which things are done, but that they had a sense that the backlog was being cleared. ‘€œWe are really seeing a sense of urgency and focus for the first time in years,’€ said Beaumont.

Kirti Narsai, head of scientific and regulatory affairs at the Pharmaceutical Industry Association of South Africa said they were positive about the facts that the MCC was dealing with the challenges and said some patience needed to be exercised.

There is no clear picture on what the actual backlog is. In a 2008 briefing to Parliament’€™s portfolio committee on health, Hela revealed that the backlog for registration in 2003 (the number of applications received but not registered in that year) amounted to 28%. Those not registered for 2004 were 31%, not registered for 2005 were 53%, not registered for   2006 were 80% and not registered for 2007 were 98%.

Hela said at the time that there had been an increase in the number of applications and that the reason for the backlog was because the MCC was functioning as it was in 1965.

She explained that this meant the numbers of evaluators and committee members was still at 1965 levels.

Hela said at the time that the large backlog had also resulted from the previous inefficiency of the system.

She said the MCC had to maintain a fine balance as the evaluators were doing the work in their spare time, and would leave if too much pressure was exerted.

She also said the MCC had found was that there were many duplicate applications of generics under different names. That was part of the problem of differential pricing, and the different names would be registered so that the manufacturers could direct different products to different markets. She said the MCC had asked the industry to make this clear, so that only one application needed to be evaluated, and the rest would be administrative.

A report compiled in 2008 by Tshabalala-Msimang’€™s advisor Professor Ronald Green-Thompson highlighted the extent to which applications for generics were clogging up the system. I have The report that illustrates clearly a point that has been highlighted by Hela on the ‘€œtsunami of generics’€.   Very few of the dossiers in the system are New Chemical Entities (NCE), in other words, many are simply versions of the original.

According to the report, in 2003 there were 16 applications for NCEs and 508 for generics, in 2004 27 were NCEs and 563 generics, in 2005 18 were NCEs and 490 generics, in 2006 21 were NCEs and 801 generics and in 2007 22 were NCEs and 765 were generics.  

This problem was highlighted by others who spoke to What’€™s Up Doc.

Hela said at the time that critical drugs were fast tracked and registered within nine to 15 months.

Hela was also part of a delegation which presented the health department’€™s strategic plan and budget to the portfolio committee in March this year.

According to the minutes from the Parliamentary Monitoring Group Hela acknowledged the ‘€œslowness in the registration’€ of new medicines.

She said that she was giving the matter her full attention and was working towards speeding up registration, especially of antiretrovirals.

The committee grilled Hela on the impunity with which those peddling complementary medicines operated.

She said that complementary medicines were not regulated, but that the MCC was looking into ways to strengthen the regulations.

She also said that a matter would only be followed up if the remedy was being dispensed on a large scale.

Sources said that some role-players with a stake in the complementary medicines market had resisted MCC attempts to cancel the so-called call up of 22 February 2002.

The 2002 directive from the health department to manufacturers and distributors of complementary medicines to submit information on their products to the department’€™s medicines regulatory body was introduced with the goal of auditing the complementary medicines market over six months.

The notice expired six months later, but manufacturers and marketers of these products continue to submit their information in terms of the expired call up with evidence that no audit ever took place.

Earlier this year the Health Products Association of Southern Africa lodged an official appeal to the decision to rescind the 2002 call-up via its legal advisors.

It feared that if recision was put into practice it would have a major impact on the complementary medicines industry effectively making approximately 15 000 products illegal.  

An industry source said that negotiations were taking place and that the HPA would have input into the notice rescinding the call-up.

Eagles and Hela also failed to acknowledge a letter sent last year by South Africa’€™s top pharmacology experts and academics warning that the market is being flooded with all kinds of quack remedies and dubious ‘€œmedicines’€.

The five-page letter warned that the information submitted continued to be accepted by the Medicines Regulatory Affairs Cluster of the health department and as a consequence these products are freely marketed without any regulatory oversight.

They said that in the absence of independent assessment it was unknown whether the products contained any active ingredients, contained toxic health metals, were possibly contaminated with bacteria or banned substances, contained scheduled substances or whether formulations were rational or safe.

However, others have said that the Simply Slim case showed why the matter was urgent. After being ordered by the MCC to remove the product from the market, the manufacturer simply revised it and returned it to the shelves, in defiance of the MCC.

‘€œThere is no evidence before the MCC that any work has been done on this product, it’€™s unbelievable,’€ a source said.

In February the diet pill was recalled with immediate effect for safety reasons.

Beeld newspaper had reported that the slimming product, which claims to be 100 percent herbal, contained sibutramine.

According to health regulations, any pill containing sibutramine must be registered as a prescription medicine and must contain no more than 15mg sibutramine.

Tests showed Simply Slim contained 27mg of sibutramine. Side effects of sibutramine include an increased risk of heart attacks and strokes.

An industry source who asked to remain anonymous expressed concern over the current backlog in the registration of medicines. ‘€œThere are huge backlogs and long delays, up to 40 months,’€ he said. The international average for the registration of drugs is between 20 and 22 months.

The MCC has also come under pressure from those who have an interest in seeing antiretrovirals registered. Earlier this year HIV stakeholders called on the MCC to speed up the registration of the critical anti-HIV medication or face legal action.

The Southern African HIV Clinicians Society sent an appeal to the health minister to intervene and address the MCC registration process which they described as the single biggest obstacle to getting affordable access to medicines. They claimed that some drug dossiers had been in the MCC pipeline for years.

President of the Society Dr Francois Venter warned at the time that the drugs on the list included all fixed dose combinations especially those that will be on the state’€™s first line regimen.

A new Medicines Control Council was recently appointed with a number of new members. However, sources pointed out that the maximum period for membership of the MCC as per legislation is 10 years.   Three of the people including the chair Peter Eagles have done 10 years and have been appointed for a third term.

Health-e  managed to speak to Mandisa Hela more than a week ago. During the telephone conversation Hela agreed to answer a list of questions via e-mail and agreed that the journalist could follow-up with a telephonic interview. However, Hela failed to respond to several attempts to reach her via her cellphone, her assistant in Pretoria and e-mail. These are the questions:

1.         How is the campaign to clear the backlog going? Can you supply some figures on what the state of the backlog is and the inroads you have made? On average, how long does it take for a drug to be registered? What is being done to clear this backlog? When are you hoping to get on top of the issues and are some categories of medicines receiving priority treatment? How did we get to a point where you faced a massive backlog and how did you solve it?

2.         There has often be criticism that South Africa insists on testing drugs that have already been registered by the FDA in the US and other regulatory bodies in Europe. Can you explain why it is necessary for SA to re-assess these drugs and why it is not a waste of time and resources?

3.         There are numerous complaints of medicines waiting years for registration, eg. Atripla. This is now affecting the ARV tender, because until Atripla is registered, generic equivalents of it are unlikely to be registered.

4.         What are you doing to improve the efficiency of the Medicines Regulatory Authority?

5.         What skills are in shortest supply and which of the expert committees are able to make headway and which are struggling to get through the amount of paperwork required?

6.         What is going to happen with complementary and alternative medicines – will new regulations be prepared; will new primary legislation be needed; what can be done in the meantime to protect vulnerable patients against exploitation and risk (e.g. from Simply Slim type operations)?

7.         There are a plethora of charlatans offering unregistered medicines for not just AIDS, but a range of medicines. What is being done to strengthen the Law Enforcement Unit to reduce these illegal activities?

8.         What is being done about the 2008 Amendment Act and the establishment of SAHPRA – will the existing Act be sufficient or will Parliament have to pass new legislation; will the necessary people be found to create the new Authority, and how will the transition be handled?

9.         The 10-point Plan mentions a review of the NDP (1996) – how and when will that be tackled properly?

10.   Can you explain why it took so long for the new members of the MCC to receive their letters of appointment? There was a time where we had no MCC in office?

11.   Pharmaceutical companies are upset because registration takes so long. They claim that they at times wait so long for registration that their patent rights are almost expired by the time they receive registration. This means their window period to make a profit is reduced and they have to make up their losses elsewhere ‘€“ in the end the consumer pays. What is your comment on this?

12.   Doctors are concerned that new, important drugs, especially for ICU and cardiovascular patients, take very long to be registered and lives are being endangered because of the delays ‘€“ this while these drugs are registered across Europe and the US? Why is this happening?

13.   How strict are you about the registration of bio-equivalent generic ingredients in light of the high number of poor quality generic ingredients (from China and India) flooding African markets? Is this a priority for the MCC?

14.   Section 4 of the Medicines Act states that:
“A member of the council or of a committee . . . shall declare his or her commercial interests related to the pharmaceutical or health care industry and shall recuse himself or herself from any discussion or decision-making to which the said interests relate or may relate.”
Do members of committees or of Council routinely recuse themselves as prescribed by the Act? Is there any record of Professor Eagles having recused himself from discussions or decision-making (in Council or the Complementary Medicines Committee) relating to products sold by Clicks while he was still a non-executive director of Clicks? Why do members of committees or Council not routinely recuse themselves when possible conflicts of interest may arise?

15.   What was the outcome of the investigation into the allegations that the late Advocate Mulaudzi accepted a bribe? Is it possible that other members of the MRA are involved in corruption? [The wife of a Council member apparently runs/owns the laboratory used by the MCC for testing. Is this true?]

16.   The 2003 Medicines Act includes registration of medical devices. How many devices have been registered in the last (nearly) 7 years? [No regulations have yet been published for registration of devices. Why not?]

17.   How can manufacturers and other members of industry decide for themselves that a product is a complementary medicine and therefore only needs to comply with the abbreviated complementary medicines call up process? Who double checks the claim that a product is a complementary medicine is in fact a complementary medicine, and hasn’t already been called up for registration as a conventional medicine? [Simply Slim refers]

18.   Is it true that some generic medicines are registered without any bioequivalence studies having been done comparing them to the South African reference product? Please explain.

19.   Is it true that some medicines are registered even though the documentation may only have been given to Council members on the same day of the meeting? How do the members manage to apply their minds to such documentation (often running to hundreds if not thousands of pages)? Please explain.

20.   Some members of the MRA have very close relationships with representatives of the pharmaceutical industry. How are these relationships monitored? Does the MRA see its primary task as serving the industry or serving the South African public?

21.   What has happened to the many millions of Rands the MCC has been paid since 2003? Why isn’t this money being used to employ more staff or to pay more academics to assist in the various committees?

22.   It is said that there is a member of the Complementary Medicines Committee who uses a SCIO machine on members of the public. SCIO is unproven and is a device that is not registered. How can the MCC have such a person as a member of one of its committees? (www.scio.co.za)

Timeline

1965

The Medicines and Related Substances Control Act ‘€“ the Medicines Act ‘€“ is passed establishing the Medicines Control Council.

1960s and 1970s

Every category of medicine for treating major diseases is called up for registration.

1972

Johan Schlebusch joins the MCC starting as an inspector (medicine controller).

1981

Professor Peter Folb appointed chairperson of the MCC. He is a leading international expert on drug safety and an outstanding scientist.

1984

Schlebusch appointed registrar of the MCC.

1991

The MCC tries for the first time to regulate medical devices and complementary medicines.

1994

US Congress passes the Dietary Supplement Health and Education Act that deregulated the supplement industry, making it easier to sell diet remedies and other dubious products alleged to improve health.

1996

Then Director General in the health department Dr Olive Shisana chairs a meeting of alternative practitioners to discuss their concerns. The concern was that such a meeting fell under the MCC and not the health department. The health department was thought to have undermined the MCC’€™s authority by hosting this meeting and rumours were flying that change was in the offing.

The sellers of complementary medicine seized on this time of uncertainty and illegal medicines started pouring onto the market.

Drug policy is published for the first time in South Africa.

1997

MCC convinced Shisana to change her mind and Schlebusch mooted a plan that would have brought the market back under control. The plan never saw the light of day.

1997

Wide-ranging changes to the Medicines Act introduced which the pharmaceutical industry opposed, resulting in years of litigation.

The MCC stood firm against Mbeki on the false AIDS medicine Virodene. The MCC suspended a clinical trial of Virodene which had proceeded without the approval of an ethics committee or the MCC.

1997

Precious Matsoso joins the MCC.

1998

Folb was not re-appointed after his term of office expired. Schlebusch and his deputy Christel Bruckner, both who had been with the MCC for over 20 years, were dismissed. Professor Helen Rees replaced Folb and Matsoso replaced Schlebusch.

2001

A CCMA award reinstated Schlebusch and Bruckner and the labour court made it an order of the court. The department reached a monetary settlement with Schlebusch, but continued to refuse to reinstate Bruckner in an appropriate position. She bought a contempt of court against the department, minister and director general.

2002

The MCC publishes a notice in the Government Gazette superseding all previous calls for registration of medicine in the same class ‘€“ the previous call-up notices for herbal drugs (1973), special foods for which a claim was made (1974), products using the terms medicated, medicinal, medical use etc (1978), and vitamins and minerals (1985) were superceded. This allowed quacks to claim that their concoctions were ‘€œregistered’€ with the MCC as they had lodged an application.

2003

The court sentenced Dr Manto Tshabalala-Msimang and Dr Ayanda Ntsaluba to 15 days in prison for contempt (re the Bruckner matter), but the sentence was suspended. Bruckner was reinstated and is still there today, but is not assigned any substantive work.

Peter Eagles appointed chairperson of the MCC.

2004

Matsoso leaves the MCC and joins the World Health Organisation.

The Code of Practice for the Marketing of Medicines is published for the first time in terms of the drug policy. This has never been finalised and leaves the door open for some of the marketing practices seen today with complementary medicines.

2005

After repeated calls the MCC’€™s registrar Dr Humphrey Zokufa claims they are investigating the operations of German vitamin seller Matthias Rath. These claims were exposed as being untrue when the Treatment Action Campaign went to court. It turned out that there was no investigation into Rath’€™s actions, including his unethical clinical trials.

Zokufa leaves the MCC in November and becomes CEO of the Board of Health Care Funders.

2006

It emerges that health department director general Thami Mseleku has been appointed interim registrar as a stop gap measure to avoid any further delays in the registration of medicines.

The acting head of pharmaceutical planning in the health department, Mandisa Hela is later appointed registrar, a position she still holds.

2008

The health department proposes the introduction of regulations dealing with the registration of complementary and alternative medicines differently from scientific medicines.

The Medicines Act is revamped, but had not yet been brought into force.

The new Act is passed but not implemented. This will pave the way for the establishment of a new authority, more independent of the health department.

Barbara Hogan is appointed health minister. She sets up several task teams, one which has the task of examining the legislation and problems linked to drug regulation It is headed by Matsoso and includes several well respected experts in the field, including Folb.

• Some of the information has been sourced from Debunking Denialism by Nathan Geffen (Jacana 2010)

Rath and the MCC

Former president Thabo Mbeki and his health minister, the late Dr Manto Tshabalala-Msimang will be remembered for their destructive response to South Africa’€™s AIDS epidemic. They caused massive confusion among people living with HIV, by casting suspicion over the toxicity to antiretrovirals opting to rather promote untested, so-called natural remedies.

On at least two occasions the MCC came under huge pressure with political meddling obvious for all to see.

The first involved German vitamin seller Dr Matthias Rath who arrived on South Africa’€™s shores in 2004. His mission was initially to repeat the success he had achieved in Europe and the United States, where he sold his untested remedies to mostly elderly people as prophylaxis against cancer and other lifestyle diseases.

On several occasions Rath had been repudiated by international scientists and research bodies either for quoting their work out of context or for making false scientific claims to back his products. Setbacks, sanctions and repudiations from highly regarded scientific journals, research foundations and courts were mostly met with disdain and long, rambling epistles to his followers.

He managed to establish his products in South Africa despite the fact that several countries were opposed to their distribution for not being classifiable as nutritional supplements, medicines or foods.

Rath used his tried and tested tactics in South Africa. His massively funded campaign centred around unsettling desperately ill people’€™s beliefs in one system, in this case antiretrovirals and Western medicine, while offering an alternative, his VitaCell multi-vitamins, coupled with what he described as good nutrition.

This message found favour with Tshabalala-Msimang, who had taken it upon herself to promote a mix of beetroot, African potato, garlic, lemon and olive oil as alternatives to ARVs with gospel-like fervour, despite international derision.

Even when a shipment of VitaCell, the multi-vitamin Rath had earmarked for distribution, was impounded by port authorities in Cape Town on the grounds that it was not classified or registered, he managed to find a loophole. In the opinion of the port authorities,

Rath required a letter from the MCC to confirm the product’€™s status as either a medicine or foodstuff. A Rath employee made contact with the deputy director of the Food Control Directorate in the Health Department, Antoinette Booyzen, claiming that Rath was intending to bring a multi-vitamin preparation into the country with no associated claims and without any medical endorsement by a doctor.

Booyzen ruled that because the levels of nutrients contained in the product were low and no associated claims were made, VitaCell was a foodstuff and did not fall within the ambit of the MCC. She then released a letter signed by herself on behalf of the director general Thami Mseleku confirming this. This letter paved the way for VitaCell to enter South Africa.

When a journalist later contacted Booyzen, she was shocked to learn that the dosages initially indicated to her by Rath and those claimed on the bottle were different. In fact, the dosages on the bottles being distributed were mostly double those given to her. The bottles had clearly been re-labelled at some stage, with the original label indicating lower levels than the later one. Rath had also failed to share with Booyzen his true intentions ‘€“ that he would be marketing VitaCell as an alternative to ARVs. Later it would be revealed that his foot soldiers were advising patients to take very high dosages.

Rath fired his first public salvo on World Aids Day, 1 December 2004, when he placed a full-page advertisement in the Mail & Guardian. It slammed ARVs as toxic and accused the Treatment Action Campaign and MCC of being ‘€˜Trojan horses’€™ for the ‘€˜drug cartel’€™. It was the first of many similar attacks.

According to sources attempts by the MCC to react to Rath’€™s accusations were blocked by the minister and her DG.

Rath later placed a double-page advertisement in a Durban newspaper, boldly sharing details of ‘€˜clinical trials’€™ that he had conducted in Khayelitsha, claiming results were so significant that they had to be published without delay. In the advertisement, he alluded to blood tests and clinical examinations, yet no ethics committee had sanctioned the human trial of Rath’€™s products, as required by this country’€™s scientific protocols.

A month later, a brash Rath published the ‘€˜findings’€™ of the Khayelitsha ‘€˜trials’€™ in the New York Times and International Herald Tribune. Two weeks thereafter, South African members of parliament found an information pack from the Dr Rath Health Foundation Africa in their pigeonholes with the same details.

After much pressure the MCC did announce in April 2005 (three months after being told) that it was investigating Rath’€™s claims. MCC registrar Humphrey Zokufa, a trained pharmacist, announced that the Council would act with ‘€˜a sense of urgency’€™ in response to a complaint laid by the TAC.

Although Zokufa and Mseleku stated on more than one occasion that an investigation was ongoing, court papers later revealed that, by Mseleku’€™s own admission, the so-called investigation entailed two telephone calls, one to Anthony Brink (at the time a Rath employee) and another to Anthony Rees (who was at the time no longer employed by Rath). Rees denied ever receiving such a phone call.

In fact, in a clear sign that the Health Department did not want the investigation to lead to anything, its chief investigator, Lionel Snyman, who was making moves to arrest Rath, was hurriedly pulled off the case. No report into the so-called investigation has ever been released.

Many believed that the MCC had failed South Africans by not investigating Rath and that they allowed political meddling.

Source: The Virus, Vitamins & Vegetables ‘€“ The South African HIV/AIDS mystery. Cullinan and Thom (Jacana 2009)