FDA's Inactive Ingredient Database and the limits on excipients

Propylene glycol, a common solvent, appears 81 times in the current edition of FDA's Inactive Ingredient Database, once for each combination of route and dosage form in which an approved drug has used it. For an ordinary oral tablet, the highest daily exposure on record is 64 mg. For an oral solution it is 22,602 mg. For a topical cream it is 76,000 mg.

Those figures come from GxRadar's analysis of the file on FDA's Inactive Ingredients Database download page³, last updated in October 2026. The file has 9,076 rows covering 1,795 ingredient names across 60 routes of administration.

For generic drug makers, the database matters most at the front door of the approval process. FDA's refuse-to-receive guidance⁶ says the agency will reject an application outright if it uses an inactive ingredient "at a level that exceeds any of the inactive ingredient database (IID) listings" without an accepted justification.

What the database records

FDA describes the database as a list of excipients used in approved brand and generic drugs, whether or not those products are still sold, "if no safety concerns have been identified." According to the agency's July 2019 draft guidance¹, it began as a paper inactive ingredient guide in 1987 and moved online in 2003. Ingredients in biologics are not included, and an April 2025 FDA presentation⁷ added that products sold under over-the-counter monographs are left out too.

Each row pairs an ingredient with a route and a dosage form and gives one of two numbers. Maximum potency is the largest amount used in a single dosage unit, or the highest percentage for creams and similar products. Maximum daily exposure, or MDE, is the most a patient would take in a day at the labeled maximum dose. The draft guidance gives a worked example. If the largest capsule on record holds 500 mg of an excipient and the label allows two capsules a day, maximum potency is 500 mg and MDE is 1,000 mg.

When FDA has an MDE, it shows that figure instead of potency. "Since MDE is a better reference, MDE will be displayed rather than maximum potency for those excipients for which MDE is available," the agency wrote in its 2019 questions and answers on the database⁵. It added that MDE values were expected only to rise as data accumulate, with a decrease occurring only to correct an error.

Another 1,206 rows give no number at all. Of those, 849 show "NA" and 357 show "ADJ PH," which appears to mark pH adjusters. The draft guidance says some values are left out on purpose, for example when a pH adjuster is listed in the formula as a "quantity sufficient" amount or when the entry is a device component, such as a transdermal patch membrane.

The 2019 overhaul

Much of the current shape dates to the second round of generic drug user fees. In the GDUFA II commitment letter, quoted in the draft guidance¹, FDA promised that by Oct. 1, 2020 users could query MDE by route and that the agency would "post quarterly notice of updates made." Our explainer on GDUFA covers how those commitments are negotiated.

FDA started by cleaning up terminology. FDA's 2019 Q&A⁵ said the database had kept "remnants of old terminology along with new terms," and that adopting one standard set of route and dosage form terms would collapse it "from 14,000+ to about 10,000" entries. GxRadar's comparison bears that out. The April 2016 download file has 13,822 rows and 3,218 distinct ingredient names. The October 2026 file has 9,076 rows and 1,795 names. The two files are organized differently, and FDA tied the shrinkage it expected to standardized terms, so the counts should not be read as excipients leaving use.

Each download now comes with a change log. The one in the October 2026 file has 301 rows spanning the third and fourth quarters of 2026. FDA's FAQ page⁴ says the database is updated "by the tenth working day of April, July, October, and January."

How generic applicants use it

For a generic application to be received, an excipient level is considered justified "if the proposed level is at or below the amount indicated in the IID for the corresponding route of administration," according to the refuse-to-receive guidance⁶. An applicant that wants to go higher has two practical options. It can cite a specific approved product that uses the ingredient at or above that level by the same route, or it can point to an FDA reply to a controlled correspondence saying the level is acceptable, with no more than three inactive ingredient questions per request.

Some dosage forms have their own rules in the guidance. Oral liquids should not be justified by comparing percentages, because the amount delivered per dose cannot be read from a percentage. The applicant calculates the amount per dose or per day from the brand's labeled dosing instead. For creams and other topicals, percentages in the database can be cited but must be converted to amounts such as mg/g.

An excipient never used before by a given route is a different problem. FDA's regulations at 21 CFR 314.127¹⁰ list "an inactive ingredient that has not been previously approved in a drug product for human use by the same route of administration" among changes that may raise serious questions of safety or efficacy. The refuse-to-receive guidance says such a product will generally need to go through the 505(b)(2) pathway instead of a generic application. FDA's Division of Filing Review still listed an unjustified excipient level among the major deficiencies that lead to refusal in an April 2026 presentation⁹.

For pills, generics can and often do use different fillers, binders and dyes than the brand, which is one reason a generic pill can look different. For injectables and eye and ear drops, FDA rules require the same inactive ingredients at nearly the same concentrations (see Q1/Q2 sameness), and the database limit applies on top of that. Our piece on what a generic must share with its brand covers the general rule.

Where FDA says the database stops

FDA is blunt about the database's limits. Maximum potency "does not represent a maximum permissible daily intake or acceptable daily intake of the excipient," the draft guidance¹ says, and the database carries no information on pediatric use or on acute versus chronic dosing. It also never reveals any product's formula. The guidance notes separate legal caps that still apply, such as the 5 mg a day cap on elemental iron set in FDA's color additive rules.

The April 2025 presentation⁷ by FDA reviewers called it "a common misconception" that a proposed MDE is justified simply because it does not exceed the listing for the route. One case study described an oral product for long-term use in children and adults. The applicant first proposed 640 mg a day of an excipient, matching a listing for short-term use in adults. FDA cited the gaps in duration and patient population in its first-cycle review (the letters behind such cycles are covered in complete response letters for generics). The application was found acceptable on a later cycle at 80 mg a day, supported by a published developmental toxicity study.

FDA's database mailbox, the same presentation said, will not say which application a listing came from, disclose a brand's formula, or rule on whether a proposed level is acceptable. Questions about a specific product in development go through controlled correspondence to the Office of Generic Drugs.

What comes next

The guidance on using the database has been a draft since July 2019, according to FDA's guidance page². At a public workshop on June 8, 2026, an FDA presenter described developing AI-powered tools, noting that such tools "can reliably extract inactive ingredient information directly from the approved RLD labeling and drug reviews," according to the workshop slides⁸, to cut manual data entry. Under FDA's published schedule, the next quarterly update of the database is due by the tenth working day of January 2027.