Primer Offered For Scientists Bringing Drugs To Market

FASEB speakers teach scientists about drug development and urge researchers to shape the regulatory process WASHINGTON--Biochemists isolating novel chemical compounds could use a bit more street smarts if they want to raise the profile - and budgets - of their research, according to university and industry scientists attending this month's annual meeting of the Federation of American Societies for Experimental Biology. Speaking at a symposium on the "Impact of Federal Agencies on Drug Development," the scientists tried to bring other researchers up to speed on the Byzantine and often dilatory process of drug development. And they warned that understanding how Congress and the federal government works - especially getting a grip on the requirements for Food and Drug Administration (FDA) approval - can be even more confusing. Scientists doing basic research tend to be hobbled by their ignorance of the world outside the laboratory door, said panelist Darrell R. Abernethy, a clinical pharmacologist at Brown University. He said he believes they need to educate themselves in two areas. First, scientists who develop new chemical and biological substances should understand how a substance is transformed by a pharmaceutical company into tomorrow's drugs. This knowledge will help them show Congress that their research can "help people" and, therefore, deserves to be funded, said Abernethy. Second, Abernethy and other speakers worried that federal laws regulating drug development and use as well as prescription drug sales could hinder work on potentially useful compounds by limiting such things as federally funded research on drugs derived from human substances or by dictating which drugs a pharmacist may dispense. Scientists savvy in the ways of Washington can better breach what Abernethy called the "chasm between science and regulation" - and can better shape legislation that affects their own research interests. Many scientists, though brilliant in their ability to isolate chemically interesting substances, are slow to see a discovery as a potential "drug," according to Abernethy. Discovery is just a starting point. There are then four steps needed to transform a novel compound into a therapeutic entity, said pharmacologist Robert Ruffolo, of SmithKline Beecham in King of Prussia, Pa. During the first step, researchers identify the molecule - such as a cell receptor - targeted by the substance. Next they try to determine the target's medical and biological significance by pinning down what happens in the body when chemical meets target. The third step is to isolate or design a version of the molecule that will do the job more efficiently. The fourth step is to test the drug for toxic side effects, first on animals and then in humans. Scientists should be prepared to wait a long time to see their compounds approved as drugs, warned clinical pharmacologist Daniel Azarnoff, of Azarnoff Associates in South San Francisco, Calif. It takes 10 years, on average, he said, to carry a drug from its initial synthesis through research and development to final approval by FDA. The price tag is typically about $200 million. The long road to drug development is intimidating, but naive scientists are even more likely to get lost on the serpentine path that leads to FDA drug approval. That path now has additional forks that can confuse scientists, according to former FDA Commissioner Arthur Hayes. A recent so-called parallel track proposal allows some AIDS patients to be treated with promising drugs before testing is completed. A 1987 regulation also allows patients with life-threatening diseases such as AIDS or certain cancers to be treated with experimental drugs. And a change in 1988 allows early drug approval for patients with life-threatening diseases. So, Hayes said, it is understandable that scientists find it hard to understand the FDA approval process. Hayes suggested that Congress simplify the system. But he and other speakers warned that Congress is being influenced by well-informed special interest groups, including those concerned with AIDS, to complicate the process. They urged scientists to become more vocal themselves. "They can't just sit back in their labs passively clucking their tongues," said William Abrams, a clinical pharmacologist at Merck Sharp & Dohme Research Laboratories outside Philadelphia. Scientists across the country should learn about Washington's ways, he said. They must master the workings not only of FDA, but also of other government sectors that have a role in drug development and use. Only then will scientists be able to shape federal policy that affects economic incentives for research, such as prescription reimbursement standards. "What these people do, can and will affect your job," said Abrams. He illustrated his point by pointing to a slide of federal agencies stacked pyramid style in a multilayered flow chart. The chart traced the path of power from the administration and Congress, through the Department of Health and Human Services, to FDA and the National Institutes of Health, where scientists lap up the last trickles of influence. "For anybody who can figure out the workings of the immune system," he added, "this should be a piece of cake."

Primer Offered For Scientists Bringing Drugs To Market

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