January 26, 2023
The FDA Inactive Ingredient Database (IID) is heavily used by formulators when developing drug products. This resource has been available since 19871 and has since informed the inactive ingredient (excipient) selections and concentrations made by formulation scientists to avoid regulatory hurdles.
The FDA IID: “provides information on excipients present in FDA-approved drug products” and “If an excipient is used in approved drug product for a particular route of administration, the excipient generally is not considered new and may warrant less extensive review the next time it is included in a new drug product.”1
Traditionally, the excipient limits for topical products were presented as % (w/w) but recently many listings have been changed to Maximum Daily Exposure (MDE)2, typically listed in milligrams. Developers now must calculate the maximum amount of each ingredient used based on a proposed finished product dosing regimen. A recent information request to the FDA for clarity on how MDE values were derived for the IID resulted in the following response:
“For topical products, we consider dosing information on the product label. We also consult with our clinical staff to determine patient use. However, in order to protect proprietary information submitted to FDA, we are unable to disclose the inactive ingredient maximum daily exposure calculations that are associated with the drug product.”
Based on the above response from the FDA, it will be critical for formulation scientists, and ultimately for clinical and non-clinical personnel, to come up with their own scientific justification for ingredient concentrations in new prescription topical products. This will be based on future dosing instructions such as: “apply a thin layer to affected areas once daily” or “apply a pea-sized amount for each area of the face”. This new approach from the FDA will require developers to know more about the proposed product’s end user requirements and formulate accordingly. Staying under the new MDE values may be important if drug products want to still qualify for “less extensive review”.
1. FDA Guidance for Industry. Using the Inactive Ingredient Database. July 2019. Pharmaceutical Quality/CMC. https://www.fda.gov/media/128687/download
2. FDA “Most Recent Changes to the IID Database”. https://www.fda.gov/drugs/drug-approvals-and-databases/most-recent-changes-iid-database