FDA Guidance Addresses Anticounterfeiting Measures

This article is part of PharmTech's supplement "Solid Dosage and Excipients 2010."

In July 2009, the US Food and Drug Administration issued a draft guidance for industry titled, Incorporation of Physical Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting. The document was issued in response to the agency's 2004 Counterfeit Drug Task Force Report, which called for guidance to facilitate the use of authentication technologies such as physical chemical identifiers (PCID).

"Although we have been working individually with manufacturers who have been using these technologies, we needed to get experience with these new and emerging technologies before we could provide appropriate draft guidance for industry," an FDA press officer told Pharmaceutical Technology.

The draft document discusses design considerations for incorporating PCIDs into solid oral dosage forms and information about related documentation that industry should include in new drug and abbreviated new drug applications or in postapproval materials. The document also addresses concerns regarding toxicology and the use of PCIDs in product packaging and labeling.

Manufacturers use PCIDs by including a trace amount of an inactive ingredient within an existing section of a dosage form. The inactive ingredient, explains the draft guidance, contains a unique physical-chemical characteristic that can be detected and authenticated with holography, fluorescence, or other techniques. Some examples of PCIDs include inks, pigments, flavors, and molecular taggants. Most PCIDs are already used as food additives, colorants, or excipients with established safety profiles. They can help thwart counterfeiting, which has been on the rise globally.

According to the FDA press officer, the agency has no plan to create a specific list of PCID products. The agency does, however, recommend using already approved direct food additives such as those listed in the Generally Recognized as Safe (GRAS) notification program or in the agency's Inactive Ingredient Guide (IIG) and using them at the lowest specified levels to avoid adverse reactions. The draft guidance also points out that applicants may revise the labeling or packaging of their product to indicate the incorporation of a PCID and any potential toxicological concerns .

More than 20 comments on the draft guidance were submitted to FDA by industry, standard-setting organizations, and academia last fall. The Pharmaceutical Research and Manufacturers of America (PhRMA) specifically recommended that FDA clarify in final guidance whether the use of PCIDs is mandatory or voluntary. In its comments, PhRMA questioned whether food-grade PCIDs would be robust enough as an anticounterfeiting measure and suggested that manufacturers use a GRAS or IIG material as a PCID. The association also suggested extending the guidance beyond solid oral dosage forms. Finally, PhRMA noted that FDA should clarify the role of pharmacists and healthcare providers with regard to PCIDs. Portions of the draft guidance, for instance, could be interpreted to mean that these practitioners need to confirm PCID presence before dispensing a product to a patient, said PhRMA in its comments. Practitioners could not perform such a test without specialized detection tools.

The Biotechnology Industry Organization (BIO) submitted comments as well. The organization seems to favor the use of other less-invasive authentication technologies and anticounterfeiting tools. Although PCIDs are useful in certain small-molecule products, said BIO in its comments, other technologies may "have less direct impact on the safety or efficacy of the product" and may be better suited to liquids and other types of products. Overall, the organization said it hopes other anticounterfeiting technologies and approaches will not be put aside. For example, BIO supports FDA's facilitation of a uniform national electronic pedigree/track-and-trace system. According to the FDA press officer, the agency recognizes that more than one anticounterfeiting measure is needed to combat global counterfeiting and advocates a multilayer approach that involves all parties in the supply chain, from manufacturers to pharmacists.

Both BIO and PhRMA asserted that details about PCIDs should remain confidential, especially if they are included in new drug or biologic license applications, because large numbers of people see these documents. "Without protection," said PhRMA in its comments, "counterfeiters are more likely to be able to circumvent the anticounterfeiting measure by reverse engineering the product. Hence, disclosure of the PCID (e.g., on the drug product labeling and/or package insert) becomes counterproductive [although we do acknowledge the resulting complexity of not listing an additive that may cause adverse events (e.g., allergic reactions) in a small number of patients]." BIO recommended in its comments that PCID information be included in drug master files as an alternative.

FDA is working on a final guidance document. In related news, regulatory authorities in Europe are aiming to tighten safety standards for colorants, food additives, and other excipients used in drug products by encouraging the use of more natural-based ingredients. Pharmaceutical Technology's June 2010 Report from Europe will cover the full story.