'Drug industry is as good or as bad as the regulators'

Iwan Darmansjah, Jakarta

The title of this article was borrowed from what the critics used to say about the drug industry in the 1970s. The public felt that after many years of regulation it had still not obtained reasonable guarantees about a medicines' safety or efficacy.

As an example of a history of good governance, drug regulation in the United States was the result of political pressure on the regulatory system to serious adverse reactions to drugs. It started with rampant misbranding and adulteration of medicines that created pressure to promulgate the Pure Food and Drug Act in 1906. Anyone before then could sell medicines that contained false ingredients, or that had not been proven effective as claimed.

The following landmark U.S. law was the 1938 Food, Drug, and Cosmetic Act, which was a reaction to the catastrophic marketing of sulfanilamide elixir. It was dissolved in diethylene glycol, an industrial solvent, and killed 107 children. The 1962 Harris- Kefauver Amendment to the 1938 Act was a response to the notorious Thallidomide disaster, a drug produced in Germany and prescribed in many parts of the world.

The drug was used to treat morning sickness in early pregnant women, however it resulted in babies with incomplete extremities, called phocomelia. The world was shocked because Grunenthal, the producer, seemed to have ignored this phenomenon, as it had already been seen in experimental animals. This 1962 Law was a mayor benchmark in drug regulation.

As a result of the Drug Evaluation Study Implementation program, many marketed drugs were found to be ineffective or toxic and were removed from the market. Several of these, however, are still on the Indonesian market today, showing laxity and irresponsibility on the part of the Indonesian Drug Regulatory Agency.

For some 12 years the world witnessed the ethical, respectful leadership of the U.S. Food and Drugs Agency (FDA). It was followed by other regulatory agencies around the world. Unfortunately developing countries lagged behind, with drugs becoming politicized and easy moneymakers by immoral officials.

The Prescription Drug User Fee Act (PDUFA, 1992) required drug and biologic manufacturers to pay fees for drug products and food supplement administration services. It also required the FDA to hire more reviewers to assess the applications. But this somehow became tit for tat, and evaluation times for marketed drugs was accelerated. Short-cut evaluations were applied, such as a reduced need for documents, use of more surrogate end-points in clinical trials, waiving of some long-term drug effects, etc.

Recent drug withdrawals include terfenadine, mibefradil, cerivastatin, troglitazone, Rofecoxib and Vioxx, just to name a few. "Drug withdrawals were increasing during the post PDUFA period. From 1997 through 2000, the drug withdrawal rate was 5.34 percent compared to 1.96 percent between 1989 and 1992 (pre- PDUFA) and 1.56 percent between 1993 and 1996 (immediately after the enactment of PDUFA)". Although FDA analysis refuted these figures, criticism of the FDA has escalated in recent years.

In Indonesia, governance of drugs has never been well organized. POM (Food and Medicine Control Agency), later named BPOM, after its separation from the Ministry of Health and put directly under the President's control -- never had enough or qualified manpower nor the organization to protect the public from bad drugs. The agency is exclusively manned by pharmacists (and two medical doctors given a minor role) and the role of the medical profession about who in fact should be in charge of safety and efficacy of drugs was sidelined.

The drug evaluation branch was entirely headed by pharmacists; the wrong men in the wrong place. The agency seems to be closer and more protective of the industry than of the public. Hordes of ineffective drugs swarm the Indonesian market, draining public resources for useless drugs. False drug claims and wrong doses are blatantly condoned and fill the pages of the formal drug information called Medical Information Management System (MIMS) of Indonesia.

Although BPOM has the power to regulate the industry, it does not effectively used its authority for the sake of consumers. MIMS claim that whatever is put in the MIMS list has been approved by BPOM. Unethical marketing is rampant, and BPOM is unable to control it. As long as the medical department is subordinate to marketing people, as is common in almost all drug companies in this country, the ethical situation will remain hopeless.

A pharmacist may understand a drug's action in a patient by reading a book, but he/she will never completely understand the diseased patient in which the drug is being used. This gross mismatch of such authority of domains is like what happened in the days when the local blacksmith attended to the sick. A farmer likewise may attend a sick chicken or dog, but nowadays we have veterinarians to understand zoonosis, and tell us about how a disease in an Avian species can jump to man.

Once it occurs in man it becomes the authority of the medical profession to treat the patient. Therefore, some symbiosis must necessarily exist between the two (or more) professions. A pharmacist cannot attend a poisoned patient, because this is the authoritative domain of the clinical toxicologist.

Cabinet ministers and even the President perhaps are ignorant about this mismanagement and wrongly assume that doctors should not co-regulate drugs together with pharmacists. The government and the House of Representatives (DPR) need to find out who and what agencies are in charge of drugs in other countries.

The same error happens in the management of avian influenza ("bird flu"), which partly belongs to the Ministry of Agriculture and partly to the Ministry of Health. Bird flu in animals is the domain of the veterinary surgeon, but in humans it is the domain of the physician.

But the Ministry of Agriculture is dominated by agricultural experts and they lack professional knowledge on zoonoses (science of disease in animals that may cause disease in man), which is the field of the veterinarian. So why is it that our country continues to make these basic (and fatal) mistakes?

The writer is an Emeritus Professor at the University of Indonesia.