The team from the Leiden University Academic Centre for Drug Research (LACDR) and Coriolis Pharma found that sugars used to stabilize large molecule active pharmaceutical ingredients (APIs) in formulation can form nano- and micro-scale particles.
The finding is significant, according to lead researcher Daniel Weinbuch, because these impurities have the potential to elicit dangerous immune responses in patients who receive them.
“We found that sugar excipients themselves contain nanometer-sized particles, which can damage proteins and make drugs unsafe,” Weinbuch said, adding “these nanoparticle impurities in sugar could even trigger the immune system themselves.”
“The biopharmaceutical industry needs to be aware of potentially harmful impurities in their excipients, which are added to the drug products. Also the sugar industry has a challenge to produce sugars excipients without these impurities."
He told us because the team had found "large variations in the number of NPIs between suppliers and even batches of the same supplier, testing would have to be performed batch-specifically."
Range of sugars
Weinbuch told us the impurities were detected in a range of sugars, explaining: "We found nanoparticulate impurities (NPIs) in various sugars, including sucrose, trehalose, fructose, maltose and galactose. Included were various supplies, batches and purity grades, mostly pharmaceutical-grade.
He added that: "Since testing for NPIs is not required by regulatory agencies, there is no information whether sugar-based excipients 'generally recognized as safe' are free of NPIs or not."
Sugar impurities may also explain why some API exhibit unfavourable safety profiles according to Weinbuch, who suggested techniques such as resonant mass measurement and flow imaging microscopy could be used to test the hypothesis.
If the impurities, rather than APIs, are shown to be responsible for the unfavourable safety profiles shown by failed candidates it could give developers another opportunity to win approval
Weinbuch said: "If a drug fails, it might not be due to the drug substance itself but due to an improper formulation. Using safe formulation excipients potentially gives failed drugs a second chance."
The research is available here.