FDA Publishes Guidance on Physical–Chemical Identifiers

Last week, FDA published a final guidance for pharmaceutical manufacturers that plan to incorporate physical–chemical identifiers (PCIDs) in solid oral dosage forms as an anticounterfeiting strategy. The guidance defines a PCID as “a substance or combination of substances possessing a unique physical or chemical property that unequivocally identifies and authenticates a drug product or dosage form.” PCIDs include inks, pigments, flavors, and molecular taggants.

In the guidance, the agency recommends that the PCID’s ingredients be pharmacologically inactive so that they can be treated as excipients. To minimize toxicological risk, FDA recommends that drugmakers use permissible direct food additives, food substances that are generally recognized as safe (GRAS), or ingredients listed in the agency’s Inactive Ingredient Guide that have been used in solid oral dosage forms.

To minimize the risk that a PCID will adversely affect the dosage form’s identity, strength, quality, purity, potency, or bioavailability, FDA recommends that companies add a PCID to the product at the lowest level that will ensure the dosage unit’s identification. PCIDs that are relatively inert also can minimize the potential for adverse interactions. In addition, FDA recommends that manufacturers examine the potential effect of a PCID on the product’s quality, performance, and stability.

One section of the guidance suggests that manufacturers consider the location of the PCID within the dosage form. Placing a PCID inside a core section of the product could increase the chance that it will interact with and degrade the drug substance, according to the document. FDA also recommends that drugmakers consider incorporating the PCID into a section of the dosage form that does not contain a release-controlling excipient to ensure that controlled-release formulations deliver their APIs at the desired rate.

Another section of the guidance lists FDA’s recommendations for documentation to be submitted by applicants proposing to incorporate PCIDs into new solid oral dosage forms in new drug applications or abbreviated new drug applications. The document also describes the documentation required of applicants that want to incorporate PCIDs into solid oral dosage forms as a postapproval change.

The amount of information to be provided for a PCID depends on its pharmacological characteristics, toxicological characteristics, and design, according to the guidance. Less information would be expected for a PCID that is a permissible direct food additive, a food substance that is GRAS, or an ingredient listed in the Inactive Ingredient Guide than for a novel PCID. The agency would expect to see information about items such as the PCID’s chemical composition, the rationale for selecting the PCID, how the PCID is integrated into the product, the location of the PCID in the product, and the relevant physical–chemical attributes of the PCID.