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FDA Issues Draft Guidance on Inactive Ingredient Database

Posted 10 July 2019 | By Michael Mezher 

FDA Issues Draft Guidance on Inactive Ingredient Database

The US Food and Drug Administration (FDA) on Wednesday released a draft guidance for public consultation providing recommendations for drugmakers on using the agency’s inactive ingredient database (IID) during drug development.
 
The IID is an online repository of information about excipients used in FDA-approved products and serves as a replacement for the inactive ingredient guides the agency began disseminating in the late 1980s.
 
Within the database, FDA provides information including the various routes of administration, dosage form and maximum potency per unit dose for each inactive ingredient, as well as the chemical abstracts service (CAS) number and unique ingredient identifier (UNII) for each listing.
 
According to FDA, drugmakers can reference inactive ingredients listed in the database in marketing applications as any excipient used in an approved drug product for a specific route of administration “generally is not considered new and may warrant less extensive assessment the next time it is included in a new drug product for the same route of administration.”
 
However, FDA points out that the IID “does not currently provide information regarding the different exposure models (e.g., maximum daily intake based on the dosing recommendations indicated in the labeling, safety in pediatric populations, acute versus chronic use) that may be needed” in a technical review of an application.
 
FDA also says that including an excipient in an application at a level described in the IID does not automatically mean it will satisfy requirements for allowable limits of the ingredient for all products.
 
But FDA notes that it has committed to making enhancements to the IID under the reauthorization of the Generic Drug User Fee Amendments (GDUFA II) to allow users to query information on maximum daily intake and maximum daily exposure information for different routes of administration by October 2020.
 
The guidance itself provides definitions for the terminology and nomenclature used in the IID as well as a description of how excipient data is presented.
 
“When an excipient is included in the IID, the maximum potency shown is generally described as the maximum level of the excipient per dosage unit for each route of administration and dosage form in which the excipient has been used,” FDA writes.
 
FDA also explains the difference between maximum potency and maximum daily exposure, noting that “there has been confusion over the years” regarding the two concepts and notes that some entries in the IID lack maximum potency values.
 
According to FDA, the missing maximum potency values occur in a small number of entries and are due to values being difficult to verify for “very old products” or in cases when the quantity of the excipient is variable.
 
Additionally, the guidance provides specific recommendations for referencing the IID in different application types, including investigational new drug (IND) applications, new drug applications (NDAs) and abbreviated new drug applications (ANDAs).
 
FDA, Federal Register Notice

Categories: Regulatory News

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