Scientists have uncovered a new simple way to “clean” genotoxic impurities (GTIs) in drug ingredients by mixing the solution with contamination-eating scavengers.
GTIs have been behind several major drug recalls recently – for instance the EU’s 2007 swoop on Roche’s ARV (antiretroviral) med Viracept. The phenomenon is caused by higher than normal levels of toxicity in the potent compounds, intermediates and reagents used to synthesize active pharmaceutical ingredients (APIs).
Now working with the widely-used GTI acrolein, a team from MIP Technologies in conjunction with the University of Dortmund, Germany, found that a silica and polystyrene (PS-NH2) scavenger resin could remove 97.8 per cent of the impurity given just a 20 minute reaction time.
The process caused no substantial damage to the API.
A growing need
The researchers say the paper, ‘Removal of Acrolein from Active Pharmaceutical Ingredients Using Aldehyde Scavengers’, is a reaction to a growing industry need, specifically after the EMA (European Medicines Agency) issued guidelines on the Limits of Genotoxic Impurities in 2006.
Under the guideline, a 1.5μg per day intake of GTI is considered an “acceptable risk”.
“Pharmaceutical genotoxic impurities (GTIs) may induce genetic mutations, chromosomal breaks, or chromosomal rearrangements, and have the potential to cause cancer in human,” the team, led by MIP’s chief technology officer Ecevit Yilmaz, said.
“Therefore, exposure to even low levels of such impurities present in the final API may be of significant toxicological concern.”
The team also said that though the resin is currently readily available – labelling scavenger resins a “a well-known approach” – more research must be carried out if the process is to be used on a commercial scale.
The study – published in Organic Process Research & Development – looked at other resins besides PS-NH2, which has a high degree of cross-linking.
It found the less cross-linked polymer-based scavengers are more selective in their scourging, they showed an “undesired high level of nonspecific binding to the API.”