From the Editor: Isn’t It Time to Update cGMPs?

Aug. 3, 2006
FDA needs to improve its public communications and to connect older written guidances, such as cGMPs, to its new initiatives.

By Agnes Shanley, Editor in Chief

“Even if you’re on the right track,
you’ll get run over if you just sit there.”

– Will Rogers

IN JUNE, the U.S. Food and Drug Administration (FDA) celebrated its hundredth anniversary quietly, with commemorative programs and a retrospective on its Web site. In the post-Vioxx, FDA-bashing era, the Agency wasn’t about to get carried away.

Unfortunately, not too many people cared all that much. Then, in the midst of all the staid festivities, came a blast from Rep. Henry Waxman whose office released a scathing report charging that FDA enforcement activity has weakened considerably during the Bush Administration (see "Waxman Thrusts, FDA Parries, No One Wins").

Ignoring completely the concept of risk management, the report suggests that U.S. lawmakers still judge FDA’s effectiveness based on the number of 483s it issues rather than overall improvements, like police chiefs who judge traffic cops based on the number of tickets they issue, rather than decreases in accidents on their beats.

Unfortunately, this misunderstanding is the Agency’s own fault. Why, for example, has FDA been so quiet about its Pharmaceutical Inspectorate training program? It may have issued a few general press releases, but the Agency could be publicizing this program to the hilt, particularly with lawmakers but also with the public.

And why have FDA’s recent initiatives — including 21st Century GMPs and the Critical Path — been greeted by such indifference from the public, the media and government officials?

In the age of the 60-second sound bite, positive internal change is no longer enough. It’s time to talk about that change, more openly and with more details, to the public, and to communicate more effectively about the whole concept of risk management as it applies to drug regulation — including the quantitative aspects.

It’s time to allow the press more access to FDA leadership and inner workings, rather than simply issuing the terse official statements that, all too often, pass for Agency communication.

And it’s also time for more colorful slogans that actually capture the public’s imagination.

If that seems like trivial spin-doctoring, consider what happens without colorful slogans. How many people today remember the Intensified Drug Inspection Program (IDIP) of the late 1960s, which stepped up FDA inspection standards, improved inspector knowledge and actually led to the FDA 483 form (combining information that had previously been recorded on two separate forms, the 2275 and the FD-483, into one handy document)?

Was this program important? Yes, undoubtedly.

Was it sweeping? No. Not anywhere near as broad and ambitious as the paradigm-shifting Critical Path, PAT or 21st Century cGMPs. But even these grander projects may end up in the dustbin of history, or as subject of some future FDA retrospective that nobody outside of the Agency really cares about, if they aren’t nurtured.

Drug manufacturers need to hear more from FDA, in the form of updates on guidances written long before the Agency’s brave new initiatives. Right now, an elite group of companies is connecting the dots between older written guidances and the use of process analytical technologies (PAT) and adaptive control. Others aren’t going to “go there” without a little more guidance from FDA.

FDA has already recognized its role in making the U.S. pharmaceutical industry technology averse. Can it take the next step and rework some troubling passages within the text of key regulations? Could it even be time to rewrite sections of cGMPs, to help shake up the bureaucracy (see "Silencing the cGMP Priesthood") that has grown up around them and is stifling, not only creativity, but common sense, at a number of drug companies?

cGMP regulations have not undergone extensive amendments since 1978. And all the bureaucracy surrounding cGMPs can make us lose sight of the fact that, like most of the FDA regulations now in place, cGMPs are important, and rooted in past events that actually injured or killed consumers. Consider, for example, the requirement for theoretical and actual yield determinations, which many companies today may view simply as a measure of process efficiency. In fact, the primary reason why yield determination is a cGMP requirement is to prevent deadly mistakes. In 1941, Winthrop Pharmaceutical’s failure to check yields resulted in a mixup of sulfathiazole and phenobarbital granulations that killed about 100 people. After that incident, such controls have been required in all NDAs submitted to FDA.

FDA had much to celebrate during its 100th anniversary. The Agency has reason to be proud of its history and its accomplishments in improving the public’s safety. But it shouldn’t be afraid to make its current initiatives more accessible and important to the public, and more “actionable” for the industry.