FDA Announces New Rules To
Expedite Testing of Drugs 

ANNA WILDE MATHEWS and RON WINSLOW
Wall Street Journal 12jan2006

The Food and Drug Administration announced new guidelines for the preliminary phases of drug development, including how to manufacture small batches of experimental medicines and conduct very-early-stage studies of such compounds in patients.

The moves, unveiled today, are aimed at replenishing the thinning pipeline of new drugs.

Health and Human Services Secretary Mike Leavitt said in a statement: "The recommendations announced today will help more researchers conduct earlier, more-informed studies of promising treatments so patients have more rapid access to safer and more effective drugs."

Though invisible to patients and investors, the early stages of testing are critical to drug development. The FDA estimates that the work done to prepare a request to allow human tests of an experimental drug currently costs $500,000 to $1 million. Manufacturers may examine thousands of compounds and only bring a few into human tests.

The agency says it wants to encourage drug companies and academic researchers to explore more possible treatments and get better information about them at the beginning of the development process. Last year, the FDA approved 20 new drugs, down from 31 the year before, not including biotech drugs. (See the FDA statement.)

Early indications on a drug, before it is given to humans, may be misleading — and manufacturers risk tossing away promising treatments before they commit the funds for a large-scale clinical trial. For instance, Pfizer Inc.'s blockbuster cholesterol reducer Lipitor, now the world's top-selling drug, performed no better in animal tests than one rival already on the market and several others then in advanced human studies. That led officials at the former Warner Lambert Co. to question whether its prospects justified the expense of mounting human studies.

An impassioned plea from the scientist who led the Lipitor development effort persuaded the company to give the drug a try in humans. After that, it took just a handful of healthy volunteers to show that Lipitor was especially effective in lowering cholesterol in humans. (See related January 2000 article.)

The FDA issued new manufacturing standards for researchers or companies that are making small batches of experimental drugs, likely in a laboratory setting.

Currently, academics would theoretically have to meet the same paperwork and other requirements that a drug company faces when it makes hundreds of thousands of doses of a medicine in a factory. Those formal rules can include requirements that academic researchers often can't meet practically — such as storing each raw ingredient of a drug in a different room, or maintaining two separate laboratories with one dedicated solely to confirming quality measures. The new guidelines might still require separation of the ingredients for a particular experimental drug made in a lab but wouldn't require different rooms.

Separately, the agency laid out guidelines for very early stage "exploratory" studies of experimental drugs. Currently, drug makers do extensive testing, including lots of laboratory and animal studies, before they apply for FDA permission to test medicines in people. Now, the agency is laying out some limited circumstances in which companies could do less research — for instance, testing the experimental drug in just one kind of animal — before asking the FDA if they can do a human study.

But these more flexible requirements would only apply in cases where the human study was very limited — likely seven days at most, in a small number of people — and the agency would scale the testing requirements to the potential risk of the human studies. For instance, the "exploratory" standards could apply to studies done with very tiny doses.

The new guidelines may draw criticism from patient advocates, since they will likely have the effect of reducing the testing that drug developers do before giving their experimental medicines to humans. However, risky early-stage studies, such as those in which people are given large doses to find the maximum amount of a drug they can tolerate, would not fall into the "exploratory" category.

The new guidelines for "exploratory studies" aren't aimed at showing whether the drug works. Doses would be too small and the studies too short. Instead, they are intended to enable companies to get an early read on questions like the so-called pharmacokinetics of drug — whether it latches on to its targets or hangs around in the body long enough to have a potential effect. The exploratory studies would still need approval from an institutional review board.

"Getting a compound to see if there is decent pharmacokinetics is a huge hurdle," says Adrian N. Hobden, president of Myriad Pharmaceuticals Inc., Salt Lake City. "A lot of drugs will fall out in" early human testing "because the drug is immediately eliminated from the body." To have that happen after spending $2.5 million is particularly frustrating, he adds.

Reducing redundant animal studies would also lead to cost savings, Dr. Hobden says, but he says such steps should be taken only in circumstances when assurances can be given to healthy volunteers who are the first humans to get a drug that they won't be put at any added risk.