Earlier this year the headlines were dominated by news of products that were withdrawn after the detection of tiny glass particles – or lamellae – in vials. In January, for example, US drugmakers Luitpold and Cumberland both pulled contaminated products.
And in 2010 Sandoz, Amgen and Baxter all recalled vials this year after glass flakes were discovered in their products. Furthermore, vials with glass particles and cracks were cited in a US Food and Drug Administration (FDA) warning letter issued to Bristol-Myers Squibb.
In the new document the agency says that it developed the advisory because while these incidents have not been associated with any adverse events the presence of fragments in injectable medications does pose a risk for patients.
“There is potential for drugs administered intravenously that contain these fragments to cause embolic, thrombotic and other vascular events; and subcutaneously to the development of foreign body granuloma, local injection site reactions and increased immunogenicity.”
“[The] FDA advises drug manufacturers of products to re-examine their supplier quality management program with the glass vial manufacturers to assure that this phenomenon is not occurring.
“Further, the Agency reminds finished drug product manufacturers that current good manufacturing practice regulations require that drug containers not be reactive or additive so as to alter the safety or quality of the drug.”
Imperfections
The new advice aims to help drugmakers mitigate these risks which it suggests are caused by imperfections on the surface of vials, such as pits and deposits arising from high temperature manufacturing, are the primary cause.
The agency also highlighted high pH drug formulations as a significant factor, particularly those products in which citrate and tartrate buffers are present.
The FDA also reveals that the length of time the inner surface of the vial has a direct correlation to the level of lamellae formation for such drugs.