FDA uses more than lab analysis of APIs to find fake drugs; excipient variation a major clue.(Counterfeiting)

ATHENS, GA -- Laboratory analysis is only one tool in FDA's armamentarium of weapons to combat counterfeiting, including excipient source and grade, an FDA chemist told the International Good Manufacturing Practice conference here last month.

Cheryl L. Flurer, Ph.D., of FDA's Forensic Chemistry Center in Cincinnati, OH, told the meeting at the University of Georgia College of Pharmacy about the agency's "multidisciplinary approach. to providing a large amount of information about authentic, counterfeit and diverted drug products.

She said the Forensic Chemistry Center's task is to determine: a) the presence of active ingredient(s); b) whether the product is consistent with authentic products; and c) whether the product is similar to other submissions. Noting that counterfeit dosage forms have been found across product and company lines, Flurer provided a list of 23 common pharmaceuticals, including Procrit, Singulair and Lipitor, with counterfeit dosage forms found in the United States.

Their examination involves objective and subjective analysis and begins with API identification based on physical and chemical distinctions. In addition to comparing packaging/labeling, FDA may also refer to drug identification websites, the Drug and Poison Control Center and the PDR for physical comparison. Methods for chemical distinctions include FTIR, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS).

Multidisciplinary counterfeit analysis is not limited to the laboratory or testing procedures. Flurer's presentation, Evaluation of Suspect Dosage Form Pharmaceuticals, also noted, "Further characterization may depend on how often this product has been, or is likely to be, subject to counterfeiting." Additional considerations include the number of different sources for the product, the number of web sites for the product and the how many times it's been seen at the Center.

Further testing may also be needed for quantification of active ingredient, impurity profiling, identification of impurities, identification of excipients, determination of product formulation, determination of residual solvent(s), elemental profiling, dissolution testing and documentation of tablet morphology and imprints by image analysis. An example of results was presented for 99 samples of counterfeit Viagra analyzed since 2007. The findings included 37 sub-potent, 40 super-potent, 17 potent and 5 mixed/wrong actives.

Following API identification it must be determined if the drug is approved for use in the U.S., which can raise the possibility of diverted drugs. Flurer explained, "A diverted product is a legitimate product; however, it is not approved for distribution in the U.S." In the case of diverted pharmaceuticals FDA will also determine whether it can distinguish between U.S. market and non-U.S. market products.

Diverted products can be identified when there are different sources of excipients or different grades of excipients used for the manufacture of non-U.S. products. This can be determined by ICP-AES or ICP-MS analysis.

Flurer advised that counterfeit drug analysis may also involve differentiating one manufacturer site from another, which becomes important when the API is manufactured at more than one facility. In the case of multiple manufacturing sites it could be discovered that an impurity peak is consistently larger in the product made at one particular site. Additionally, different excipients may be used at different locations and may be identified using FTIR.

Flurer presented tables showing the types of counterfeit drugs that FDA has found in the U.S.

By Tara Y. Coyt

Atlanta Correspondent

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