FDA's Current Position about Melamine Contamination in Pharmaceutical Excipients

Melamine (also known as cyanuric acid amide or 2,4,6 triamino-1,3,5 triazine) is an excipient manufactured in large quantities and mainly used as additional chemical in the furniture industry and in the manufacturing of resins. Since the scandals from 2006 and 2008, where melamine was detected as illegal extender in wheat gluten (an ingredient for pet food) and milk powder (partly used in baby food) from Chinese production, the substance has become one of FDA's focus as a dangerous contamination of pharmaceutical excipients. As a consequence of a potential hazard for the patients' health, the FDA published in August 2009 the "Guidance for Industry: Pharmaceutical Components at Risk for Melamine Contamination".

Like in other past scandals where people suffered damages or even died (e.g. contaminated Heparin or diethylene glycol in cough syrup), the presence of melamine couldn't be clearly detected with the common methods. The Guidance for Industry expressly presents test methods which have been published by the FDA.

These analytical methods (HPLC, LC-MS/MS, and GC-MS) are specific and sufficiently sensitive to reliably determine melamine up to 2.5 ppm concentrations. In this context, the FDA published on the Internet in the Q&A section updated questions and answers about appropriate analytical methods for detecting melamine. Beside referring to the Guidance for Industry, the FDA's position also focuses on the fact that drug manufacturers should perform risk-oriented controls. This concretely means that already the sampling procedure and also the analysis should consider that possibly:

• Melamine impurities are not uniformly spread
• The source for the impurity/ contamination is to be found in the raw material used for the manufacture of the excipient.

The analytical methods recommended by the FDA are not binding though. In certain cases, less sensitive methods can be appropriate too provided the use of such methods can be justified.

Please also see the FDA Q&A webpage

and the "Guidance for Industry: Pharmaceutical Components at Risk for Melamine Contamination" for further information.

Additional information is also available on the FDA site on analytical methods developed by the FDA Field Laboratories to detect melamine.

Author
Dr Gerhard Becker
Concept Heidelberg (a service provider entrusted by the ECA Foundation)