Despite their passive treatment role, drug excipients sometimes are the active agent in recalls. In a presentation at the recent ExcipientFest, Steven Wolfgang of the FDA's Center for Drug Evaluation and Research said that component variability and low levels of impurity have been drivers. The event organizer, the International Pharmaceutical Excipients Council, has made available presentations from the event on its website.
Wolfgang described five recalls during 2010 that were caused by excipient dissolution failure. Of the five, two are over-the-counter drugs. Of these, one involved an aldehyde impurity and the other variability in the properties of the corn-based coating component, Zein.
Intra-batch variability in the ethylcellulose used in a capsule coating was responsible for two of the recalls, according to Wolfgang's presentation. And the final excipient-based recall he mentioned was caused by excess acidity of the matrix carrier (Glyceryl Behenate) used in a microsphere formulation.
Wolfgang also notes in his slides that high levels of peroxide--which can degrade APIs and lead to drug sub-potency--led to a drug safety advisory for the binding agent Crospovidone last October. The FDA detected levels 30 to 40 times higher than normal and discovered that the manufacturer was not monitoring for the impurity. The incident led to a USP monograph revision.