Q1/Q2 sameness, the recipe rule for generic injectables, eye drops and creams

Section 6703 of the Consolidated Appropriations Act, 2026¹, a spending law enacted on Feb. 3, 2026, that also carried the federal PBM rules, changed what FDA must tell generic drug makers about their formulas. When FDA decides that a proposed injectable or eye drop does not match the brand's inactive ingredients, the agency must now name "the ingredient or ingredients" responsible and, where an amount is off, state "the amount of such deviation."

Until then, FDA's standard reply could be far less specific. In a February 2025 training presentation⁴, an FDA scientist showed the agency's template response for a failed formulation, which told the applicant only that its formula "is not Q1/Q2 the same as the RLD with respect to one or more inactive ingredients."

Q1/Q2 is shorthand for qualitative and quantitative sameness, meaning the same inactive ingredients in the same amounts as the reference listed drug. For most pills the rule does not apply, and generic tablets routinely use different fillers, dyes and coatings. For injectables and eye and ear drops it does. In GxRadar's count of Drugs@FDA records¹⁰, 194 of the 648 original generic approvals in calendar 2025, about 30 percent, were injectable, ophthalmic or otic products. Another 26 were topical. The full approval series is on GxRadar's approvals page.

What the regulation requires

The federal drug law itself does not require a generic to use the brand's inactive ingredients, as FDA notes in its November 2025 guidance on pH adjusters⁶. It bars approval when inactive ingredients or the composition make a generic unsafe. FDA turned that into route-specific rules in 21 CFR 314.94(a)(9)², with matching refusal-to-approve provisions in 21 CFR 314.127(a)(8)³.

FDA's documents call the permitted categories exception excipients. FDA explained the stricter treatment when it proposed the rules in 1989, in a passage it quoted again in the 2025 guidance⁶: "each parenteral, ophthalmic, and otic drug product represents an individual pharmaceutical system with its own characteristics and requirements." Our piece on what a generic must share with its brand covers the rules for pills.

How FDA measures sameness

Q1 is about identity. FDA's 2025 presentation⁴ says reviewers look at each ingredient's name, grade and salt form, and may ask for comparative test data for ingredients that change during manufacturing, such as the biodegradable polymers in long-acting injections, one reason many of these products count as complex generics.

Q2 is arithmetic. FDA's Office of Generic Drugs "interprets quantitative sameness to mean a concentration that is within 95 percent to 105 percent of the reference listed drug concentration," according to the pH adjuster guidance⁶. The test is the percent difference between test and reference, (T minus R) divided by R. If a brand injection held 2.00 mg/mL of a stabilizer, a generic could hold between 1.90 and 2.10 mg/mL. Processing aids and manufacturing overages fall outside the comparison.

Matching the brand does not settle everything. FDA's refuse-to-receive guidance⁵ says an ingredient that is quantitatively the same but exceeds the agency's inactive ingredient database limit for that route still triggers a refusal, and warns that "the assumption should not be made that any listed IID concentration incorporates the 105% Q1/Q2 allowance."

How applicants find out before filing

Companies can test a formula through controlled correspondence before they file, and the refuse-to-receive guidance⁵ asks for no more than three proposed formulations per request. The 2025 presentation⁴ laid out the replies FDA gives.

Eye drops get stricter treatment than the regulation's text suggests. Despite the exceptions written into the rule, FDA "has determined that, as a scientific matter, any qualitative or quantitative deviations from the RLD should be accompanied by an appropriate in vivo BE study or studies," the 2016 guidance⁵ says. In an April 2026 presentation⁸ on filing problems, FDA's Division of Filing Review still listed a "non-Q1 and/or non-Q2 formulation" among the major deficiencies that lead to refusal. Our explainers on bioequivalence and on FDA's product-specific guidances describe the studies involved.

The pH adjuster exception

Acids and bases added to set a product's pH have a guidance of their own, because the regulation does not list them among the exceptions. FDA published a draft guidance on April 14, 2022, and finalized it in November 2025, according to the agency's guidance page⁷. It lets applicants request a waiver under 21 CFR 314.99(b) for a qualitative or quantitative difference in pH adjuster in an injectable, eye or ear product. FDA's stated view is that pH adjusters "function in such a way that, in some circumstances, a waiver" may be appropriate. The waiver covers pH adjusters only.

Topicals and other products

For creams, gels and other topicals, the regulation asks for the same inactive ingredients without a fixed concentration test, and it allows different ones if the applicant characterizes them. Sameness still matters in practice. FDA's 2025 presentation⁴ notes that product-specific guidances for products outside the injectable, eye and ear categories "sometimes recommend specific BE approaches that may be suitable when formulation is Q1/Q2 to the RLD." The regulation also flags, as a change that may raise serious questions of safety or efficacy, a topical vehicle change "that might increase absorption of certain potentially toxic active ingredients."

What the 2026 law changed

Section 6703 adds a new subparagraph to the generic drug provisions of the Food, Drug, and Cosmetic Act. According to the enrolled text¹, it covers drugs that regulations require to share the brand's inactive ingredients in the same concentrations, and drugs for which FDA accepts an in vitro bioequivalence approach that depends on such sameness. On request, FDA must say whether the product is Q1/Q2 the same, and if not, name the ingredient and the size of any quantitative gap.

A favorable answer is also locked in. Once FDA says a formula is Q1/Q2 the same and the application is filed, the agency cannot change that finding unless the brand's formula changed and the old version was withdrawn for safety or effectiveness reasons, or FDA documents an error in writing. FDA's April 2026 Generic Drugs Forum presentation⁹ said the requirement applies to controlled correspondence, pre-ANDA meetings, applications and post-approval supplements pending on or submitted after Feb. 3, 2026.

The disclosure duty took effect on enactment. The law gives FDA one year, until Feb. 3, 2027, to issue draft guidance on how it determines Q1/Q2 sameness, "including with respect to assessing pH adjusters," followed by at least 60 days of public comment and a final guidance within a year after comments close.