Questions & Answers Regarding Enhancements to the Inactive Ingredient Database (IID)

1. How will the IID change?

   Several changes are planned in 2019 as we phase in enhancements to meet our GDUFA II commitments (see page 17 of the GDUFA II Commitment Letter). In Phase I, the terminology for routes of administration (ROA) and dosage forms (DF) will be standardized for consistency.  The current version of the IID does not have standardized terminology for routes of administration (ROA) and dosage forms (DF). In the updated IID, we’ve chosen a single standard set of terms for ROA and DF. These terms are found on the FDA’s web page for use in Structured Product labeling (SPL).  The number of entries in the database will collapse from 14,000+ to about 10,000.   

2. Why are ROA and DF terms changing in the IID?

   It is necessary to select a single data standard for identifying routes of administration (ROA) and dosage forms (DF) to accurately compare the levels of excipients (to select the highest potency) in each ROA and DF for the IID. The IID has been published for over 30 years. During that time, FDA’s terminology has evolved. But the IID had retained remnants of old terminology along with new terms. This resulted in an unnecessarily long list of ROAs and DFs for each excipient which made the IID confusing. By adopting a single, current data standard, the IID is more accurate, shorter and easier to understand.

3. What other changes will users see in 2019/2020?

   By October 2020, the IID will include maximum daily exposure (MDE) of excipients for which MDE is available.  The IID will also include a change log that identifies changes made in each publication and what information was replaced.

4. Will the MDE and maximum potency come from the same sources?

   No. The two values are not linked. The maximum potency currently shown in the IID comes from multiple approved products containing the excipient. It is the highest amount of the excipient per dosage unit. Maximum daily exposure also comes from multiple products containing the excipient but is based on a calculation of excipient exposure due to maximum daily dose. Since products that are dosed multiple times a day leading to a maximum daily exposure may not be the same as those products with the highest unit dose amount of the excipient, there will not be a link between maximum potency and maximum daily exposure. It should be noted that the IID algorithm retrieves the largest value of each excipient for each route of administration and dosage form in FDA’s master database but does not reveal the formulation of any product.  

5. Will the changed IID display both maximum potency and MDE for each excipient?

   No. The purpose of the IID is to provide users with excipient levels that may be referenced for drug development. Since MDE is a better reference, MDE will be displayed rather than maximum potency for those excipients for which MDE is available.

6. Will MDE continue to change as more data becomes available?

   Yes. Maximum daily exposure (MDE) values will be added gradually as data becomes available. However, any change is expected be an increase in MDE values as more data is obtained, not decrease. A decrease would only occur to correct an error, and this is unlikely to happen.