In the prepublication of the Federal Register today, the FDA asked for comments on issues related to trying to reduce the confusion on maximum daily intake (MDI) and maximum daily exposure (MDE) limits in its Inactive Ingredient Database (IID). The industry uses the IID to identify the level of inactive ingredients that may be safely used in a drug product. The IID currently classifies safe levels of ingredients by the routes of administration and dosage form, and, in many instances, MDI and MDE. The prepublication of the FR notice can be found here.
The Agency recognizes that the IID is a helpful resource but there is a need to prioritize new entries as well as provide additional data on MDI and MDE levels. But, before the FDA takes steps to move forward, it is seeking input on what makes the most sense to industry users. One suggestion is that eliminating the route of administration would help reduce the confusion as such a search could yield long lists of entries. However, since the route of administration and dosage form could be important information in determining whether the safety of the inactive ingredient has been previously evaluated by the Agency for a specific route of administration (e.g., topical, oral parenteral, ophthalmic, etc.), such information may be critical for product development activities.
The Agency is asking that interested individuals or companies provide input to the docket on the following questions:
- Should FDA focus on adding MDE information for certain excipients? If so, which excipients should be prioritized for inclusion of MDE information and why?
- Should FDA focus on prioritizing excipients used in certain categories of drug products (e.g., oral or topical products)? If so, which categories and which specific excipients used in those categories should be prioritized and why?
- Is dosage form information in the IID helpful to your drug development program? If so, please explain how dosage form information in the IID is used in your drug development program.
- Is the current structure or format of the IID difficult to navigate? If so, how can it be improved?
These are all important issues as the FDA continues to improve the utility of the IID. In my opinion, removing the dosage forms and routes of administration may hinder drug development as it could blind developers or steer them in the wrong direction in understanding the maximum levels of ingredients in topical vs. oral medications. Perhaps the search feature could be designed to tease out the inactive ingredient levels and MDI and MDE exposure to include specific dosage forms and routes of administration.
As the FDA works hard to find the most efficient and useful way to add this essential information, give it a hand and provide your comments along with examples of how the IID has helped or failed in your drug development experience.
