An overview of the drug development process

Physician Executive, May-June, 2005 by Ross Tonkens

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The FDA takes, on average, about a year to review a typical, non-expedited NDA, give or take a few months. It may approve the proposed labeling, approve modified labeling, send the sponsor back to conduct additional special, or even pivotal trials, or may refuse approval outright (though, usually it will warn the sponsor if that is likely, giving them an opportunity to withdraw the NDA).

Sometimes the FDA will give conditional approval but require additional post-marketing trials to answer specific additional efficacy or safety questions.

In addition to mandated conditional regulatory approval or post-marketing surveillance trials, other reasons sponsors may conduct post-marketing trials include:

* Comparing with competitors (prove non-inferiority or superiority)

* Widening population (pediatric)

* Changing formulation or dose regimen (antihypertensive-diuretic combination, or new extended release formulation of already marketed compounds)

* Applying a label extension (such as expanding indication, e.g., Paxil[R] for obsessive compulsive disorder, Serafem[R] for premenstrual dysphoric disorder, Neurontin[R] for diabetic neuropathy)

Even when an NDA is approved unconditionally, regulatory scrutiny of a drug does not end. In most countries, yearly safety reports must be filed with the applicable regulatory agencies as long as a drug remains on the market, and these agencies independently monitor drug safety.

If safety concerns arise, the FDA may demand withdrawal of a drug from the market at any time (terfenadine {Seldane[R]}, cisapride {Propulsid[R]}, and cervistatin {Baycol[R]}, for example).

The author wishes to thank regulatory expert, Raymond Huml, MD, legal expert, Judith Beach, and communications advisor, Jay Johnson, for their valuable assistance in preparing this manuscript, and to PhRMA, Pharmaceutical Research and Manufacturers of America, for permission to use the "Stages of Drug Development" graphic.

By Ross Tonkens, MD

Ross Tonkens, MD, is global scientific head of the cardiovascular therapeutics division of Quintiles, an international pharmaceutical research organization.