Latest Improvements in FDA’s Inactive Ingredient Database Include Change Log and Use of Maximum Daily Exposure

FDA’s latest efforts to improve the functionality of its Inactive Ingredient Database (IID) include a quarterly log to track changes in the records and the use of the term “maximum daily exposure” (MDE) in lieu of “maximum potency.”

The change log creates a way for users to track changes made to the IID, such as the MDE for potency replacement, on an on-going basis. Notices are posted each quarter and include each change made and the information that replaces it. First posted in October 2019 as a static PDF document, the change log was updated in June 2020 to a searchable interactive list.

FDA defines “maximum daily exposure” as the total intake of an excipient over a 24-hour period when a product is used as labeled, where “maximum potency” is the highest excipient amount in a unit dose of an approved product. The introduction of the MDE approach is intended to provide applicants with more complete information about the acceptable level of a particular excipient in a drug product. The algorithmic calculation of MDEs is an on-going process at CDER and the maximum potency values are being replaced as these calculations are completed.

A webinar sponsored by IPEC-Americas in September provided the opportunity for CDER Office of Pharmaceutical Quality (OPQ) Office of Policy for Pharmaceutical Quality (OPPQ) Branch Chief Susan Zuk to highlight the recent progress made and considerations that warrant further attention. She is the CDER lead on the IID and its improvement efforts.

The session was moderated by industry consultant Kathy Ulman, who serves as a technical specialist for IPEC-Americas and is vice-chair of its Regulatory Affairs Committee. Ulman also plays a liaison role in IPQ’s coverage of the excipient regulatory issues and the council’s activities.

The webinar was one of four held by IPEC-Americas during the latter part of 2020 in lieu of its annual Excipient World Conference, originally scheduled to be held in May. The other three webinars addressed: ● the failure of enteric coatings in vivo ● excipient toxicology in the 21st Century, and ● filing an application with a novel excipient. [Recordings of the four webinars are available on the IPEC-Americas website.]

The Excipient World webinar on the in vivo problems of enteric coatings, originally aired in June 2020,  was presented by University of Alberta PhD Candidate Daniela Silva, based on the research she is involved with at the university’s Drug Development and Innovation Center. Her invitation to present at the 2020 conference followed a presentation she gave on this formative research at a June 2019 excipient workshop held at Health Canada (HC), in which IPEC-Americas was actively involved. [See IPQ March 20, 2020 for a review of Silva’s presentation and the other highly informed presentations and discussions on prominent excipient CMC issues that took place at the HC workshop.]

The other two Excipient World webinar took place in July. The 21st Century excipient toxicology issues were addressed by Johns Hopkins University Bloomberg School of Public Health Professor Thomas Hartung. At the other webinar, Merck Engineering Associate Director Kara Quinn shared the experience with a filing where the novel excipient designation issues surfaced inadvertently.

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