The meeting was opened by Dr Jonathan Quick, Director of the Department of Essential Drugs and Medicines Policy (EDM) who welcomed more than 90 participants from all continents, from differing backgrounds, including public health, regulation, the innovative and generic pharmaceutical industry, government, and UN organizations. He spoke of the tremendous interest fuelled by fixed-dose combinations (FDCs) for antiretrovirals (ARVs) and also by recent experiences related to malaria and TB products.

He noted the long history of FDC production. One of the most far-reaching events of the 20th century occurred in May 1960 with the marketing of the first combined oral contraceptive (COC) in the USA. This was also one of the first widely marketed blister packed products. Maloprim (pyrimethamine + dapsone) was developed as a malaria prophylactic agent with activity against parasites that had become resistant to pyrimethamine alone in the early 1960s. In 1969 cotrimoxazole (Bactrim or Septrin) was launched as an FDC antibiotic which resulted from the cross licensing of components by Wellcome (now GSK) and Roche. This compound was the top antibacterial of its time (grossing more than US$5 billion in sales).

During the 1960s the pendulum began to swing away from FDCs. The FDA was mandated to review the effectiveness of drugs approved between 1938 and 1962 in the Drug Efficacy Study Implementation (DESI) Programme. This resulted in medicines being withdrawn and new FDCs facing a difficult passage to registration.

In 1978, the first WHO Expert Committee on the Use of Essential Drugs laid down demanding criteria for inclusion of FDCs. These were:

• clinical documentation of efficacy
• therapeutic effect greater than the sum of the components
• cheaper than the sum of individual products
• improved compliance
• dosage adjustments possible for the majority of the population.

Every Expert Committee maintained this position until 2002, when it changed to: “Most essential medicines should be formulated as single compounds. Fixed-dose combination products are selected only when the combination has a proven advantage over single compounds administered separately in therapeutic effect, safety, adherence or in delaying the development of drug resistance in malaria, TB and HIV/AIDS.

Jonathan Quick reminded participants that FDC products are not limited to AIDS, TB or malaria. One recent blockbuster has been an FDC asthma inhalant. And a recent controversial BMJ article has proposed a 4-FDC “polypill” for the primary or secondary prevention of heart disease, which could be for everyone over the age of 55!

Especially in the area of HIV/AIDS but also for TB and malaria, FDCs have been identified as highly desirable in terms of adherence and ease of treatment, containment of resistance, reducing diversions and possibly reducing costs.

The purpose of the meeting was to bring together the many different groups with an interest in FDCs to share information and propose how WHO and its partners could work to address barriers and to optimize the benefits of FDCs. The areas to be discussed at the meeting were reviewed. These included the scientific issues around the production of FDCs, and issues of compliance and adherence, patents and licensing, production and formulation, and quality and regulation.

There had been debate on whether to have multiple small meetings for each of the three diseases or to have a single large meeting. It was decided to hold a large meeting because of the interaction between the issues and the actors. Individuals working on malaria, TB and HIV/AIDS were coming to EDM to discuss the same technical issues and were often unaware that problems had been solved by other disease groups.