The FDA has published final guidance on the use of excipients as anti-counterfeiting tools in solid oral dosage forms.
Inactive ingredients can give solid oral dosage forms unique and identifiable physical and chemical properties that differentiate genuine products from fakes. Companies adopting this strategy now have a regulatory framework from the US Food and Drug Administration (FDA).
“If an applicant incorporates a physical-chemical identifier (PCID) into a solid oral dosage form, we recommend that the ingredients be pharmacologically inactive”, the FDA said in its final guidance .
The FDA suggests generally recognised as safe (GRAS) excipients, colorants and food additives as possible PCIDs. Taking this precaution limits the likelihood of pharmacological or toxicological complications.
Measures should also be taken to make sure the quality, potency and bioavailability of the drug is unaffected by the anti-counterfeiting ingredients. The FDA recommends cutting the chance of adverse interactions by using the smallest quantity of ingredients needed to authenticate the drug.
Using unreactive ingredients as PCIDs will also help cut interactions. Manufacturers must consider these issues and include reasoning for choosing the PCID in regulatory submissions to the FDA.
The level of detail needed in premarketing or post-approval submissions depends on the PCID. If the PCID is used as a food additive or GRAS less justification is needed than for a novel ingredient.
Requirements for products that are already on the market are slightly different. Post-approval PCID submissions must be backed by analysis of how the product’s impurity profile has changed through addition of a new ingredient.
The FDA also wants long-term and accelerated stability studies to assess impurity formation and the dissolution profile. “One should conduct such stability studies through the drug product expiration date, although the studies need not be completed prior to submission of the change”, the FDA said.