SA Medicines Bill Approved Amid Widespread Condemnation

The controversial South African Medicines and Related Substances Amendment Bill 2008 was approved by the Parliamentary Portfolio Committee on Health this week.


Although the Bill still has to go before the full Parliament in September, it is expected to be passed into law.


The amendment establishes a new State regulatory authority, the South African Health Products Regulatory Authority, replacing the Medicines Control Council (MCC). The MCC is currently the national competent authority for the approval of new medicines to be marketed in South Africa.


The controversial aspects of the new law are its granting of ultimate decision-making authority to the Minister, its changes to the appeals process and ultimate authority on marketing decisions.


Under the new section 15 "Certification and registration of products", the Minister can choose to refuse approval of a new drug for marketing, after it has passed clinical trials and has been cleared by the Regulatory Authority. The Minister can refuse to register a product if it is considered contrary to the "public interest" - in this decision the Minister is to take account of:

1. public health interests;
2. economic interests in relation to health policies;
3. strategic interests in relation to health policies;
4. the need and desirability for such produch; and
5. generally whether the public would be best served by such registration.

The amendment to section 24 and new section 24A establishes a new appeals process which allows opposition on any grounds (not just scientific) to the decision of the Regulatory Authority or the Director-General. But it appears that the amendments do not provide for appeal against the decision of the Minister.

The Bill has been strenuously opposed by pharmaceutical companies and patient groups alike. It is described as replacing the role of the regulatory authority with an appeals process and a Ministerial decision. Critics have suggested that this leaves the process vulnerable to abuse, mis-use by competitors and interference from policy positions.

In particular, South Africa's track record on the approval of anti-retrovirals is very worrying if this system goes ahead. At the XVI International AIDS Conference 2006, the UN Special Envoy criticised South Africa's approach to prevention and treatment, and others called for the resignation of the Health Minister, Dr Manto Tshabalala-Msimang. The Health Minister had insisted that the South African display include garlic, lemons and African potatoes (pictured at right). Soon after the international meeting and with ongoing public pressure, South Africa appeared to respond with a change in policy but with the removal last year of more progressive Deputy Health Minister, Nozizwe Madlala-Routledge. AIDS activists called the sacking "a dreadful error of judgment." Earlier this month the Health Minister declined to attend this year's XVII International AIDS Conference in Mexico City.

Dubbed as Dr Beetroot, Dr Garlic and worse, there is a dedicated "SackManto" website and in 2007 scientists wrote a joint letter of protest to President Mbeki. But he has continued to give the Health Minister's position his full support.

Treatment Action Campaign (TAC) former chairman, Zackie Achmat, has stated that the new structure will compromise the independence of the Regulatory Authority and "will leave it vulnerable to political interference." TAC has opposed the Bill and has declared it will take action to prevent the Bill becoming law. Many groups are said to be prepared to take legal action if the Bill is passed into law in September in what is described as one of the most important pieces of health legislation in South Africa in recent years.

Thailand - Compulsory Licensing Will Continue

The Public Health Minister, Chavarat Charnvirakul (pictured right), has declared that compulsory licensing of essential medicines will continue in Thailand, despite ongoing pressure from international pharmaceutical companies.

The announcement comes after months of speculation as to whether the health policy would continue, with the election of a new government in April this year. And it follows reports of lobbying of the government by Sanofi-Aventis to purchase its product.

Wichai Chokewiwat, Government Pharmaceutical Organisation (GPO) chairman, is reported as stating that Sanofi had offered to compensate the GPO by selling its products at a discount in Thailand.

Meanwhile, The Nation has reported today that a group of 500 HIV/AIDS activists and patients have challenged Sanofi-Aventis to take its claims to the Central Administrative Court. The challenge is to put in a public forum claims made in a confidential letter to the Commerce Minister requesting a review of the enforcement of compulsory licensing of docetaxel (for which a licence was issued in January this year).

The president of the Thai NGO Coalition on AIDS, Supattra Nakapiew, is reported as stating "We want Sanofi Aventis to file a lawsuit with the Central Administrative Court because we want this case to be a test for the enforcement of compulsory licensing of life-saving drugs in the future."

Before the end of this month, a joint committee meeting of senior officials from the Public Health Ministry, Commerce Ministry and Foreign Ministry together with other interested parties (including civil society organisations and the Pharmaceutical Research and Manufacturers of America, PhRMA) will decide on solutions to access to essential medicines in Thailand and the best means by which these can be delivered.

Bird Flu Vaccine Patent

Some interesting or disturbing (depending on your perspective) news to report today as it appears that the US Government has applied for an international patent in respect of a vaccine for the treatment of influenza and in particular for the treatment of bird flu (H5N1).

The patent application was first filed with the United States Patent Office (USPTO) on February 16, 2006 as application number 60/774,923. Exactly a year later the same application was filed via the Patent Cooperation Treaty (PCT). The PCT application is numbered PCT/US2007/004506 with a corresponding publication number of WO/2007/100584.

The applicants are cited as the Government of the United States of America, as represented by the Secretary, Department of Health and Human Services -National Institutes of Health,, Office of Technology Transfer, 6011 Executive Blvd., Suite 325, Rockvillle, Maryland 20852-3804 (US) and the Government of the United States of America, as represented by the Secretary, Department of Health and Human Services - Centers for Disease Control and Prevention, 4770 Biford Hwy (K79), Atlanta, Georgia 30333 (US).

In the description of the application the applicant notes ‘The significant public health impact of Influenza A and B virus infections is compounded by the threat of emerging virus strains. Concerns exist that avian influenza virus (H5N1), endemic in poultry in Southeast Asia, may trigger a pandemic in humans should the virus evolve to spread from human-to-human’.

It goes on to state that the ‘invention provides a vaccine strategy for controlling influenza epidemics, including avian flu, should it cross over to humans, the 1918 strain of flu, and seasonal flu strains. In addition, the invention is designed to lead to a combination vaccine to provide a broadly protective vaccine'.

Whilst acknowledging the existence and availability of other patents for the treatment of bird flu, citing those owned by Sanofi Pasteur, Inc. and Chiron Corporation as examples, the applicant nevertheless proffered that there was still a concern that the production by these companies would not be sufficient to meet demands were there to be a worldwide pandemic. The applicants relied on a 2004 World Health Organization (WHO) which highlighted the need for a ‘new broad-spectrum influenza vaccine’ to treat with multiple influenza strains.

What is controversial about this particular patent application is that the new vaccine incorporates one to four genes from a H5N1 strain which was isolated from an Indonesian victim of bird flu in 2005. It goes further by also incorporates genes from flu strains in Thailand, Hong Kong and South Korea. It is worth noting that the strain that contains the genes was transferred to the WHO Global Influenza Surveillance Network (GISN) by Indonesia for characterization for public health purposes.

This is a troubling development as one of the applicants, the Centers for Disease Control (CDC) is a WHO Collaborating Centre for influenza and virus studies. The mandate of Collaborating Centres is to receive influenza viruses from donor country for public health characterization purposes. The patent application raises specific questions about the US CDC, which is a WHO Collaborating Centre for influenza virus studies. The WHO Collaborating Centres receive influenza viruses from donor countries for public health characterization purposes, and not for the purposes of making proprietary claims. The GISN’s effectiveness rests on the prompt sharing of and access to viruses from all donors. However, one wonders how many donor countries will wish to continue to share influenza viruses for research and vaccine development if it is that Governments who operate Collaborating Centres are minded to make proprietary claims over the materials which they have received as a result of the GISN system. Obviously this patent application built on the back of the GISN system of virus sharing will call into question the entire system and may very well undermine its effectiveness.

As for the application itself there are far reaching implications for developing countries especially when one considers that this particular patent application for a bird flu vaccine designates over 100 countries states, including most Latin American, African, and Asian countries.
What can be done? What of the rights of the Indonesian Government which supplied the strain from which the gene has been extracted? Does the human victim from whom the gene was extracted have a proprietary right to his gene?

It seems that it is these occurrences which strengthen the call for a reform of patent laws. It would seem patently unfair (pardon the pun) for the US Government to be able to assert ownership of a gene that was provided in good faith for public health purposes and to gain a potential financial windfall by acquiring a patent for commercial exploitation.

The developments in this one will be worth following.

Rising Drug Prices - The Real Devil in the Detail

Decisions not to supply certain drugs on national health schemes may be an inevitable consequence of a wider problem of rising prices for a growing number of patented medicines. The recent NICE preliminary decision to advise the UK National Health Service (NHS) against several high-priced treatments for advanced renal cell carcinoma was largely attributed to the high cost of these medicines.

In an article last week in USA Today it is suggested that a small number of prescription brand-name medicines in the US, still protected by patents, are being raised in price by 100-1000%. Overall, price rises last year were around 7.4% on average for brand-name drugs in the US.

While patents potentially preserve prices against oversight by conventional competition, pressure is coming from elsewhere. In December 2003, Abbott Laboratories Inc raised the price of the HIV/AIDS drug, Norvir (ritonavir), by just over 400% (from USD205.74 to USD 1028.71 for 120 capsules). In May of 2004, the US-based civil society coalition, Prescription Access Litigation (PAL) filed a class action lawsuit in Illinois state court against Abbott and in October 2004 filed a federal class action suit in the US District Court in California.

Only last week did Abbott agree to settle the lawsuit (the decision awaits approval and the final amount will depend upon the decisions of the 9th US Circuit Court of Appeals regarding the antitrust questions in the case).

But Abbott faces potentially larger damages in the lawsuit filed in October 2007 by pharmacies and wholesalers, and joined by competitor GSK. The case goes before the US District Court Judge Claudia Wilken next week.

The problem is a kind of pharmaceutical BlackBerry issue. Norvir, which received FDA approval in 1996, is a Protease Inhibitor (PI) and is an essential component in highly active anti-retroviral treatment (HAART) used to treat HIV/AIDS. Although initially marketed as a standalone PI, Norvir subsequently became more commonly used in low doses as a booster in HAART.

Abbott then introduced Kaletra around 4 years later as a fixed-dosed combination product and the only such product to include Norvir/ritonavir. The wholesale price of Norvir was then raised in 2003, but not that of Kaletra (despite containing ritonavir). Raising the price of Norvir effectively raised the price required to access the 8 out of 9 competitors' drugs that rely upon Norvir as the booster in HAART. Kaletra thus became a cheaper alternative, but not necessarily a medically-appropriate one for all candidates. The Kaletra patent does not expire until 2016.

According to reports in the San Jose Mercury News, San Franciso, internal memos at the time warned that if the price of Norvir was raised, Abbott would come off as the "big, bad, greedy pharmaceutical company."

As much as I wouldn't want to give up my BlackBerry, it seems the Norvir stranglehold puts quite a bit more at stake.

NICE Won - High Prices and New Deals

This week in the UK the National Institute for Health and Clinical Excellence (NICE), which advises the National Health Service (NHS), proposed against further use of four treatments for advanced renal cell carcinoma that has spread from the primary tumour. A final decision on the proposal is not expected from the NHS until January.



NICE applies criteria for "cost-effectiveness" which the four drugs - Avastin (bevacizumab) owned by Genetech/Roche; Nexavar (sorafenib) owned by Bayer; Sutent (sunitinib) owned by Pfizer; and Torisel (temsirolimus) owned by Wyeth - did not fulfil.


The decision has been widely criticised as the drugs present the very few options for patients with this advanced renal cancer. Charities, including Cancer Research UK, have condemned the decision. And practitioners have raised concerns regarding the effectiveness of interferon as the only treatment option remaining. Professor John Wagstaff of the South Wales Cancer Institute told the Independent that there would be no point in referring patients as around 75% gain no real benefit from interferon. James Whale (pictured), broadcaster, was diagnosed with renal cancer in 2000 and told the Telegraph "If final guidance remains as it currently stands it will certainly mean an early death sentence for many."


However Professor Peter Littlejohns, Clinical and Public Health Director at NICE, has defended the decision in a BBC report, maintaining that providing these treatments would mean forgoing treatments for other patients in other areas.


GSK, on the other hand, is said to be working to alleviate pricing obstacles to NICE approval for the drug Tyverb, used in the treatment of breast cancer. In this case as well, NICE refused to adopt the new drug despite GSK's attempts to negotiate a "risk-sharing" arrangement with the Department of Health (DH) where the DH is charged only for the proportion of patients estimated to have received significant benefits from the treatment. The UK-based pharmaceutical company is now working towards a "price-volume" deal with the DH in order to resolve the concerns with cost.


The "price-volume" proposal presents an innovation in pricing where a cap is introduced on the total cost of the medicine to the NHS, regardless of the number of patients being treated (whether it is higher or lower than the cap). The fixed price will cover the cost of the drug for several thousand patients. This price would apply if fewer patients were recruited. The NHS will therefore benefit if it identifies a higher number of patients to receive the drug.


The Financial Times describes the GSK proposal as "pioneering" at a time when pharmaceutical companies are coming under increased pressure to address pricing obstacles to adequate delivery of healthcare and patented medicines. The proposal innovates upon a conventional business model to the company's benefit of greater overall sales and to the benefit of patients in greater access to new medicines.


But this might be a bridge too far for some and a deal too late for many.

Innovations in Access - Priority, Pools and Policy

Priority Review Voucher

Amendments to the US Food, Drug and Cosmetic Act Administration (FDA) come into effect next month, with the issue of the first priority review vouchers expected. The amendments, introducing these vouchers, were proposed to provide new incentives for research into neglected tropical diseases. The bill was introduced by Senators Sam Brownback (Republican, Kansas) and Sherrod Brown (Democrat, Ohio) in 2007 and signed by President Bush in September that year.


The Food and Drug Administration Amendments Act (HR 3580) amended Subchapter A of Chapter V of the Food, Drug and Cosmetic Act (21 USC 351, et seq) inserting Section 524 and introducing a system of priority review vouchers for companies seeking to register drugs and vaccines for neglected tropical diseases.

The effect of the voucher is to gain fast-track approval for other drugs that company may seek to register in the future, potentially reducing registration times by almost a year. Following Section 524(b)(3)(B), the first voucher may be expected 27 September, ie, one year on from the date of enactment (Presidential assent).

Regulatory delays are frequently cited by pharmaceutical companies as costly inefficiencies, thereby making a system to mitigate these delays very financially attractive to the industry. However, concerns have been raised. Although the vouchers ideally become important and valuable commodities to facilitate partnerships and to sell onto other companies and thus finance clinical trials for partnerships researching in these neglected diseases (amendments in June provided for the transferability of the vouchers), some have cautioned that the system will not necessarily drive new research. Rather, in some cases they will simply entice companies to seek US registration of drugs already on the market in other countries, with the benefit to the company of a very bankable voucher without the social benefit of new research. Others even doubt the value of the voucher, suggesting that the era of the blockbuster drug is over.

The research qualifying for vouchers might also be limited, with vouchers being available only for registration of drugs containing active ingredients not previously approved. This has been noted as a potentially serious limitation of the scheme, with no incentive for research into new uses for existing formulations and new combination therapies.






Patent Pools

Another significant initiative in access also in the press is that of patent pools. Following the briefing on the UNITAID Patent Pool at the 17th International AIDS Conference, currently underway in Mexico City, James Love explains the major features of the UNITAID patent pool:

• the pool is created as a voluntary mechanism;


• patent owners have the opportunity to identify the field of use for patents licensed to the pool;


• patent owners may exclude countries to which the licence will not apply.

Patent pools are not new, one of the first dating back to the 19th century when a group of sewing machine competitors (including Singer) decided in 1856 to cross-licence rather than decimate their profits by suing each other. This kind of business model persists today and is arguably of very significant application when it comes to medicines.

The Universities Allied for Essential Medicines (UAEM) this week endorsed the scheme: "UNITAID steps forward as a visionary leader in the global fight against diseases affecting the poor." UAEM has called upon universities to endorse the scheme and to contribute to the scheme through consultation with present licensees and through reservations on future licences.

Generics remain instrumental in facilitating access to treatment in developing countries, and at a time when generics are credited as dominating the US Global AIDS initiative, concerns have been raised regarding the scope of the proposed Anti-Counterfeiting Trade Agreement (ACTA). In comments on the proposed agreement, the Generic Pharmaceutical Association (GPhA) urged the US Trade Representative (USTR) "not to allow the rising momentum behind a global anti-counterfeiting strategy to be diffused by deviating into expanded IP protection and enforcement with respect to patents and data exclusivity." Today, a sign-on letter was released by Essential Action and others, urging negotiators to publish the draft text together with pre-draft papers and criticising the ongoing secrecy of the negotiations.

Comments Invited on UK Policy in Access to Medicines

Meanwhile, research is currently taking place into UK Government policies on access to medicines, with consultation with industry, government departments and other stakeholders due to take place in the first half of September. The draft report, being prepared by Emma Back and Samia Saad, will be published in early October on which there will be further consultation later that month. The report will ultimately inform the subsequent edition of the UK's Good Practice Framework, to be managed by the Department for International Development (DFID) in conjunction with Business Enterprise and Regulatory Reform (BERR), Department of Health (DH) and the Intellectual Property Office (IPO).

Comments on key issues to consider and address are invited by the consultants. These should be provided in no more than two pages and no later than 22 August 2008. These may be sent directly to Emma Back (emma.back1@hotmail.com) and Samia Saad (samiasaad@gmail.com).

Traditional Healers Trained in HIV Health Care

The fight against HIV/AIDS in Haiti is being strengthened by a collaboration between medical practitioners and traditional voodoo healers.

Recognising the important relationship between people living in rural Haiti and traditional healers, training in identifying symptoms and advising on treatment is now being provided to traditional healers.

Since most people would consult a traditional voodoo healers for advice, Promoteurs Objectif Zéro Sida (POZ) in Haiti have launched projects to bridge the cultural and technical divide between traditional medical knowledge and western medicine. POZ also provides referral cards to the 30 healers trained in treatment and prevention advice, who sent 360 patients to the conventional HIV testing centre and clinic. (At left: Aurore Julien Brazier, community nurse at POZ's main health clinic in Montrouis)

In recognition of its work, POZ was recently awarded the UNAIDS/UNDP Red Ribbon Award, which is being presented at the International AIDS Conference in Mexico City this week.

POZ is also a partner of Alliance which works towards community action to fight AIDS in developing countries.

WHO Bulletin - Special Issue on Ethics and Public Health

The World Health Organization (WHO) has just published the August issue of the WHO Bulletin.

This month's issue is dedicated to ethics and public health, including a contribution on the ethics of drug donations from Christina P Pinheiro, Department of Hygiene and Epidemiology, University of Porto Medical School, Porto, Portugal.

Pinheiro notes the lack of international regulation on drug donation procedures and the opportunity therefore for exploitation. While the WHO has published interagency guidelines for drug donation, these are merely guidelines, not international regulations.

The large number of agencies involved in drug donations leads to undue complexity and inefficiency in the process, including unfortunate waste. For instance, in a 2006 study of Pharmaciens Sans Frontieres Comite International, it was noted that all major donations of pharmaceuticals do not meet recipients' needs.

Pinheiro criticises the origins of donations for their inappropriateness - including industry surplus, free samples and returns to pharmacies for disposal. Further problems are raised by the state in which drugs are delivered, including expired drugs and labelling in languages unknown by the local health workers. And drugs which are unusable become the burden of the recipient country, now responsible for their disposal as hazardous waste. In many ways, "free" donations can become quite costly to the recipient countries, greatly undermining the value of this procedure in many cases.

The ethical issues are clear, with an acceptance that something is better than nothing, rather than demanding the best medicines. As Pinheiro states, there is "a disturbing division between the rights and worth of different populations."