Regulatory Focus™ > News Articles > Unapproved Drugs, Faulty Tablets, Bloody Accident Lead to Warning Letter for Generics Company

Unapproved Drugs, Faulty Tablets, Bloody Accident Lead to Warning Letter for Generics Company

Posted 16 July 2013 | By Alexander Gaffney, RAC

Generic drug products have gained huge market share since the 1984 passage of the Hatch-Waxman Act, which for the first time established a pathway for the approval of generic drugs (excluding the 'Paper NDA' pathway). By many estimates, generic competitors control more than 80% of the market once they are introduced, creating a strong incentive for many companies to compete for the market share of popular drugs.

But as a recent Warning Letter from the US Food and Drug Administration (FDA) points out, sometimes even the most common of generic drugs are manufactured outside of acceptable standards.

The Warning Letter

The letter, sent to a New Jersey manufacturing site owned by Indian manufacturer Cispharma, explains that during a March/April 2013 inspection, FDA inspectors identified "significant violations" of current good manufacturing practices (CGMPs). The standards are used to ensure that a product is manufactured according to FDA regulations, resulting in a product that is pure, unadulterated, of the proper strength, uncontaminated and not deteriorated or packaged incorrectly.

While many inspections will uncover at least one minor CGMP violation, FDA's inspection uncovered a length list of them, with many reminiscent of a previous inspection conducted by FDA in 2011, the agency said.

For example, lots of the company's 100 mg Phenazopyridine HCl drug were reportedly distributed to pharmacies with 200 mg dose tablets intermingled with the correct 100 mg dose tablets. While FDA said the company concluded the error was likely due to a mix-up on the part of pharmacists, FDA said a review of manufacturing records found that the 200 mg tablets had been manufactured "just before" the 100 mg lots that had been subject to the complaint, necessitating a more thorough investigation on the part of Cispharma that did not occur.

A Bloody Accident and Terrible Tablets

In addition, there was evidently an "employee accident" involving both blood and tissue. FDA said its investigators found little to explain the incident, though the company wrote in a response that it had revised the investigation report to note "several extensive cleanings" and the disposal of all products open during the incident. However, FDA said the company had been unable to describe how it ensured that there was no blood or tissue remaining after the cleaning process.

In several other cases, FDA observed the company did not have "adequate written procedures" in place to assure that products were of the proper identity, strength, quality or purity relative to the approved application. FDA said it found a large number of deficiencies related to this point, including surface erosion on tablets, chipped tablets, peeling tablets, broken tablets, coating problems, hardness problems, and colored specks in the tablets. In many of these cases, the company did not have adequate records to explain why certain tablets were rejected, FDA added.

Unapproved Drugs

FDA's inspection also found five unapproved drugs marketed by the company. It was not clear if the company was manufacturing doses which have not received FDA approval, or if it was marketing without an approved abbreviated new drug application or new drug application under 505(b)(2) of the Federal Food, Drug and Cosmetic Act.

At the time of the Warning Letter's posting, the company still had information on its website regarding the availability of all five products.

FDA concludes its letter in unusually stark terms, noting that despite the most recent inspection having concluded in April 2012, that it felt it was still justified in issuing a Warning Letter given the "inadequacy of [the company's] 483 response, repeat deficiencies, and your continued marketing of unapproved new drugs."

FDA's Warning Letter to Cispharma

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