IPEC-America Suggests Improvements to FDA’s Inactive Ingredients Database

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PTSM: Pharmaceutical Technology Sourcing and Management

PTSM: Pharmaceutical Technology Sourcing and Management-11-04-2015, Volume 11, Issue 11

FDA’s inactive ingredients database (IID) has been under development for several years, as a way to allow generic and name-brand pharmaceutical manufacturers to check on the safety and performance of specific inactive ingredients.

FDA’s inactive ingredients database (IID) has been under development for several years, as a way to allow generic and name-brand pharmaceutical manufacturers to check on the safety and performance of specific inactive ingredients.

In the past, the International Pharmaceutical Excipients Council (IPEC) had voiced the need to improve the quality of data. For the past few years, IPEC experts have participated in a working group, together with representatives from the Generic Pharmaceutical Association (GPhA) and FDA, to help improve the database and the quality of data within it.

This week, in response to FDA’s request (No FDA 2015-20556) for comments in five key areas that would improve the database, IPEC-Americas submitted suggestions in the following areas:

Nomenclature (use of ingredient names and synonyms)
IPEC emphasized the need for consistency and searchability, which depends largely on using consistent naming.  “When ‘preferred names’ are established, all relevant synonyms associated with the preferred name should also be referenced,” IPEC-Americas working group members commented.

IPEC also recommended consistency with compendial nomenclature, which is usually required on label ingredient listings, and suggested that FDA get input from the industry on synonyms.  The council also highlighted the need to address nomenclature for mixtures of excipients which have compendial monographs (e.g., simethicone), co-processed excipients, and noncompendial mixtures.

Identification of excipient amounts
The IID currently uses “maximum potency,” or the maximum amount of inactive ingredient in a single use for each route or dosage form, to identify amounts.  IPEC experts suggested that the “maximum daily intake” be used instead, specifying the safe total quantity of an excipient to be used in all drug products for the same route of administration.

Handling updates
To ensure that any changes or updates made to the database are complete and accurate, IPEC-Americas suggested that updates be published quarterly or more frequently and that a change-management and notification process be established and published.

IPEC also noted that updates should be made as transparent as possible to show the type of update, whether it involved a deletion or addition of a listing, changes in amounts, and also suggested that a better mechanism be established to capture and correct missing data.


Restructuring the database
IPEC-Americas suggested that any restructuring should focus on the following:

1. Including database functionality and elements not currently available (for instance, additional data fields, better searchability, and standardization for definitions of certain terms)

2. Collapsing and consolidating similar dosage forms (e.g., topical ointments, creams, gels, and lotions)

3. Mapping similar, interrelated routes of administration, where potency could be cross-referenced from one to another  by bridging them with safety data (e.g. toxicological data).

Additional improvements
IPEC Americas also recommended the following:

  • Issuing a Manual of Policies and Procedures (MAPP) or guidance that would better explain FDA's use of the database for regulatory and safety considerations and decisions.

  • Working with industry to develop a template on the types of toxicology information necessary to meet FDA’s review requirements.

  • Including a mechanism for excipient manufacturer to provide such information confidentially to the Agency (where the manufacturer does not have a DMF or cannot provide the information directly to their customer due to confidentiality reasons) and allowing the use of publically available, peer-reviewed toxicology studies in regulatory filings;

  • Accepting the “family approach” for families of related grades of an excipient. IPEC also recommended posting the reviewed family information on FDA’s website and linking information to relevant IID listings.

  • Including information on pediatric use of an excipient;

  • Developing and maintaining a frequently-asked-questions blog describing IID updates, progress, and outstanding issues regarding both content and use.

Download the current IID here.