Drug Regulatory Agencies Collaborate On Counterfeits, New Medical Products

By Kaitlin Mara
BERN – Representatives from drug regulatory bodies are meeting this week in Bern, Switzerland, to discuss collaboration in an increasingly international world. Key topics of concern in the meetings include counterfeit drugs and issues in the production of new medical products.

The 13th International Conference of Drug Regulatory Authorities (ICDRA), co-organised by the Swiss Agency for Therapeutic Products (Swissmedic) and the World Health Organization (WHO) and taking place from 16-19 September, is an opportunity for drug regulatory experts to engage in private consultation: without groups, such as industry, who have a stake in their decisions, according to an organiser. The group comes up with recommendations by week’s end, which are later published online.

Industry groups and civil society were invited for a two-day pre-conference immediately before the ICDRA, focussing on one issue of key importance in drug regulation. This year that issue was paediatric medication, in particular the challenge of developing drugs and dosages for children, as children’s needs are distinct from adults, they suffer diseases to which adults are not or are less susceptible, and there are ethical questions with regards to clinical trials involving them.

Hans Hogerzeil, director of Essential Medicines and Pharmaceutical Policies at the WHO, said at a press conference on 15 September that the real problem is “nobody really makes good medicines for children.” Instead, he said, they take medicines for adults and assume they work for children, even if not properly tested. Research is complex, because a child cannot truly give permission for a trial. Also, researchers must contend with important ethical considerations, for example how to ensure continued treatment and treatment for patients on placebo after the trial.

Children often need specific formulations, especially if too young to swallow big capsules, said Agnew Saint-Raymond from the European Union Medical Agency.

Intellectual Property and Medicine For Children

One of the major worries of the intellectual property sector on drugs is counterfeit. On this problem, Hogerzeil said that it is “clear it exists” and there is no reason to believe that children’s medications are exempt from the problem. However, he cautioned, the real concern is about safety and not IP.

If you have a counterfeit that is the right medicine but with a different package, then you have a trade issue, but if you have a counterfeit that contains nothing or contains something toxic, then it is a serious concern, he explained.

Yves Juillet, counsellor to the president of the French Pharmaceutical Companies Association (Leem), who also works with the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), agreed, saying “IP is not the issue, it’s fraudulent misrepresentation” that cheats the patients who purchase the drug.

The WHO webpage on counterfeit drugs predicts that in 2010 the value of the counterfeit drug trade will have increased by 90 percent from its 2005 levels. One problem could be the increasing sales of medicines online. This is dangerous, said Hogerzeil, because “you have no idea where the medicines are coming from, or if they are registered.” Consumer advocates have elsewhere expressed concern that the danger of online medical sales is exaggerated by those who have a stake in selling higher priced pharmaceutical drugs in stores.

The difficulty in incentivising innovation on drugs for children that do not yet exist, particularly when those children are resource-poor, also is at issue.

Diabetes, for instance, said Hogerzeil, will often kill children under 1 year old in the developing world because insulin is not available; even when available, insulin must be refrigerated, which is not always possible in areas with high heat and no electricity. There is a clear human need for heat-stable insulin, but an unclear market to support its development.

But Stuart MacLeod of the Child and Family Research Institute said that while the market is “small in fiscal terms, it’s not small in population terms.” This is especially true when you look at local situations. There are, for instance, several countries in sub-Saharan Africa where more than 50 percent of the population is under 15, he said.

Further, MacLeod said, it would be “wrong to assume it’s only HIV, tuberculosis and malaria” – diseases toward which public research funds are often directed – that are problems, and that there were “obviously many other widespread diseases” of concern.

David Wood, who coordinates the Quality, Safety and Standards Team of the Department of Immunization, Vaccines and Biologicals at WHO, pointed to a Global Alliance for Vaccines and Immunizations (GAVI) study paper that said diabetes and pneumonia are the leading killers of children under 5. Wood added that the public private alliance of GAVI has helped reduce the prices of vaccines, and the syringes used to administer them.

“From an economic point of view it’s not an attractive option,” noted Hogerzeil, to produce medicines for diseases affecting those who cannot afford to purchase cures. For instance, those who are bitten by snakes and need anti-venom tend to be farm labourers, women, and children, he said: and they often lack the political power to speak up for themselves.

This is a market failure and therefore a public interest problem, Hogerzeil added, so it will need public-private partnerships to be solved. However, very little public money has so far gone into such initiatives; most investment to date has been private.

And drug development is only the first step: after it is discovered, then it must be formulated, quality norms must be set, and there needs to be a mechanism to inspect companies and countries to ensure that those quality norms are met.

Pricing Policy; Delays

Once a drug can be brought to market, there is the issue of sales prices. Hogerzeil said some of the common concerns in this area do not always manifest themselves as theorised. For instance, worry about brand name proprietary drugs have led to many calls for generic companies to step in and play a role in creating similar-quality, but cheaper and off-patent goods.

But generic companies, while good at copying, are not necessarily good at producing new medicines.

Also, fears that price differentiation between countries will just encourage export of cheaper drugs have not manifested. We have seen 35 years of price differentials in vaccines, and in family planning drugs, and no one is shipping them back to developed countries.

A good solution, he explained, is a Novartis anti-malarial drug that sells for the full price of US$72 in Switzerland, for US$18 to private-sector medical procurers in the developing world, and for US$2 to public sector care providers in developing countries. The solution is making the trade name different – so it is illegal to move developing country versions back into Switzerland – and to make the packaging different between public and private versions of the drugs so they cannot be confused.

What is a problem, he noted, was lack of harmonisation between regulatory bodies. Regulation is a “forgotten part of the problem”; regulation ensures quality but uncertainty about the specifics of national regulations can cause significant delays in needed drugs.

ICDRA events have been taking place biennially since 1980. Participants are regulatory agents from WHO member states. Discussion results are released publicly online as recommendations for collaboration, for nations, or for the WHO. Recommendations from the 12th ICDRA, for instance, include advice to national agencies to facilitate vaccine development for emerging diseases, and for the WHO to help ensure transparency on blood and blood products.

Kaitlin Mara may be reached at kmara@ip-watch.ch.