Remember how the European Medicines Agency forced Roche to recall Viracept? The reason: the EMEA learned that ethanol from cleaning products reacted with the drug’s active ingredient, nelfinavir mesylate, to form EMS, a known carcinogen. The FDA found the same thing in Pfizer’s version, which is sold in the US, but only restricted its use. Now, though, an FDA official acknowledges the same toxic contaminant could be lurking in any number of drugs already on the market, in-Pharmatechnologist reports.

Concern regarding the presence of precisely this type of contaminant prompted an FDA project to establish guidelines dictating limits for such genotoxic compounds for drugmakers, the site informs us. The guidance, due to be issued in the near future, highlights the agency’s view that these impurities represent a pressing problem in pharmaceutical manufacturing.

“There are several drug products on the market that have mesylate, besylate or tosylate salts…these are the type of drug salts that could involve this process impurity, ethyl methanesulfonate,” says Jeff Murray, deputy director of CDER’s division of antiviral products. “This involves potentially several different drug products that could finally come under the final (EMS) specification.”

“We are aware of all the drugs that have (these impurities). We have been in contact with many of the sponsors, we are aware of the manufacturing process, so we don’t expect (the levels) to be extremely high. But when we set a final limit for this then the manufacturers are going to need to make sure they are in compliance with the most strict levelsm,” he adds.

A guidance published by the EMEA in January notes tackles the problem of genotoxic impurities in medicinal products. “According to current regulatory practice it is assumed that (in vivo) genotoxic compounds have the potential to damage DNA at any level of exposure…and that such damage may lead/contribute to tumor development,” the document states. “Thus for genotoxic carcinogens it is prudent to assume that there is no discernible threshold and that any level of exposure carries a risk.”

And why the differing reactions to Viracept between the EMEA and the FDA? “This is a judgement call, and different agencies might think differently,” says Murray. “For our patient population here, which is what we have to consider, it was a risk-benefit decision…reasonable agencies come up with slightly different plans for their populations.”