FDA Publishes Guideline to Fight Counterfeit Medicines

On 13 July 2009, the American Food and Drug Administration (FDA) presented the draft for a new guideline whose purpose it is to further combat counterfeit medicinal products.

The guideline describes the use of physical-chemical identifiers (PCIDs) in solid dosage forms. PCIDs are substances or combinations of substances featuring a unique chemical or physical property that can be used for the purpose of identification. Colourants, pigments and flavours are examples of chemicals that can be used as molecular markers. PCIDs are then either meant to be identifiable by the dealer or pharmacist, or only by means of special instrumental analysis. PCIDs can either be used as markers in the dosage form itself or in its packaging. The objective of using such substances is to make it more difficult for counterfeiters to copy medicinal products.

The FDA points out that many of these potential PCIDs are already used as food additives. In order to avoid negative effects, a minimum dose of the PCID should be added, just enough to allow identification. Furthermore, the document recommends the use of substances that have no medicinal effect themselves, do not interact with the dosage form's active ingredient and can be treated as excipients. It also encourages the reader to consider a differentiation between a core section of the solid dosage form containing the active ingredient and an external section with the marker, e.g. the coating.

Apart from that, the required documentation to be included in premarketing or postapproval regulatory submissions is listed. What is, of course, required here is the proof of stability of the medicinal product containing PCIDs as well as toxicological data for the PCIDs themselves. In case of postapproval changes, comparative data for the medicinal product with and without PCID markers have to be provided.

The categories for the submission of changes range from annual reportable (AR) to prior approval supplement (PAS). The question of whether the addition of a PCID marker only has to be announced or whether the FDA's approval has to be obtained in advance depends on the result of a risk analysis by the applicant. An increased risk is anticipated if the substances are not yet known to the FDA as food additives, which requires a PAS.

The requirements are similar for PCIDs integrated into the primary packaging. Changes involving approved food additives are classified as uncritical and can be notified through the annual report. If there is insufficient proof of safety, but migration of the marker substance from the packaging into the medicinal product can be excluded, the change can be submitted in a CBE-30 supplement, in which case the FDA can make objections within 30 days. All other changes need to be approved prior to implementation (PAS).

You can find the new draft guidance here.

Dr Robert Eicher
On behalf of the European Compliance Academy (ECA)

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