The Top 12 GMP Violations

Sometimes it's process complexity, a lack of training, or carelessly done paperwork that leads FDA inspectors to cite drug companies for violating current good manufacturing practices. But at other times violations appear to be attempts to pull the wool over inspectors' eyes.

"Time, reputation and money will make people take the risk," of violating GMP tenets, says Charles Carney, a long-time GMP practitioner and consultant who is now an instructor for trade group ISPE.

Deliberate violations are in the minority, of course. "People have to be a lot more intelligent than we train them to be," Carney says. CGMPs are covered in 21 CFR parts 210 and 211 ["Drug CGMP Regulation"], he explains. "But everything else in 21 CFR applies."

Title 21 of the FDA Code of Federal regulations, "Food and Drugs," is based on the U. S. Federal Food, Drug, and Cosmetic Act. It covers food and drug regulations for the FDA,  Drug Enforcement Administration, and Office of National Drug Control Policy.

"While there are specific GMPs for drugs, biologics and devices, anything else that might apply in Title 21 should also be taken into account," Carney says.

In many cases, GMPs are straightforward. But each company writes its own procedures for implementing the practices. "The biggest failure is following standard operating procedures," Carney says. Either operators haven't looked at the latest SOPs or been trained on them, or procedures are out of date and inconsistent with regulatory expectations.

So inspectors have their work cut out for them. And they've proven themselves a highly detailed lot with long institutional memories, as the following collection of documented CGMP deviations shows. The summaries provided are a handful of those deviations cited recently. Our main criterion for inclusion is an FDA warning letter. Those included are intended to represent the variety of deviations that inspectors report. In most cases, our summaries include only a portion of what's described in a warning letter.  

With current FDA leadership promising greater transparency and shorter response times for action, it may well be time for some manufacturing-compliance housekeeping. And if the presence of FDA inspectors in Title 21 isn't motivation enough, consider the heightened interest of the executive suite: investors are bringing class actions against drug makers when the company's noncompliance with CGMPs negatively affects its market performance.