# 2025-19990: FDA Guides Waivers for pH Tweaks in Eye and Ear Drugs

2025-19990, Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use; Guidance for Industry; Availability, is a Federal Register notice from Health and Human Services Department, Food and Drug Administration published 2025-11-17, effective 2025-11-17 (as of 2026-06-08).

- Canonical: https://policyrisk.com/federal-register/2025-19990
- As of: 2026-06-08
- Plain-text twin of the page above; the HTML and this file carry the same facts.

## Facts
- Document number: 2025-19990
- Title: Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use; Guidance for Industry; Availability
- Type: Notice
- Agencies: Health and Human Services Department; Food and Drug Administration
- Citation: 90 FR 51373
- Published: 2025-11-17
- Effective: 2025-11-17
- Comments close: not stated
- Significant: no
- Touches household money: no
- Regulation identifier numbers: none
- Last updated: 2026-06-08

## In one line

FDA Guides Waivers for pH Tweaks in Eye and Ear Drugs

## Summary

The FDA just released new guidance to help companies making generic injectable, eye, or ear medicines when they want to change the pH adjusters from the original drug. This makes it clearer how to ask for permission to use different pH adjusters, speeding up approvals and possibly saving money. The guidance is effective starting November 17, 2025, so drug makers should get ready to follow these new rules.

## Abstract

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled "Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use." This guidance is intended to assist abbreviated new drug application (ANDA) applicants that reference a drug product intended for parenteral, ophthalmic, or otic use in seeking approval of a drug that is qualitatively (Q1) different or quantitatively (Q2) different from the reference listed drug (RLD) with respect to the pH adjuster(s). This guidance describes how FDA intends to evaluate a request for a waiver of Agency requirements for a Q1 or Q2 difference in pH adjuster, including recommendations on the type of information to provide in support of such a waiver request. This guidance finalizes the draft guidance of the same title issued on April 14, 2022.

## Effects PRIA read

- How to Request pH Adjuster Waivers: benefit, low. If you make generic injectable (parenteral), eye (ophthalmic), or ear (otic) medicines and want to use pH adjusters that are qualitatively (Q1) or quantitatively (Q2) different from the reference listed drug, this guidance explains how FDA will evaluate a waiver request under Sec. 314.99(b). It des…
- FDA Feedback Recommended Before Filing: benefit, low. The final guidance includes recommendations that ANDA applicants seek FDA feedback on a proposed approach for justifying a Sec. 314.99(b) waiver for a pH adjuster difference. It also recommends seeking FDA input where the applicant plans to use a particular bioequivalence approach with a formulatio…
- Confidentiality of Formulation Questions Clarified: benefit, low. The guidance clarifies FDA's obligations to maintain the confidentiality of trade secret and confidential commercial information when FDA responds to questions about drug product formulations. Applicants can expect FDA to distinguish protected confidential information in its communications about fo…
- Guidance Finalized and Published: benefit, low. FDA finalized the guidance titled 'Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use' and published the announcement in the Federal Register on November 17, 2025. The final guidance supersedes the draft issued April 14, 202…

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## Sources
- [2025-19990 on federalregister.gov](https://www.federalregister.gov/documents/2025/11/17/2025-19990/considerations-for-waiver-requests-for-ph-adjusters-in-generic-drug-products-intended-for-parenteral)
- [2025-19990 as published (PDF)](https://www.govinfo.gov/content/pkg/FR-2025-11-17/pdf/2025-19990.pdf)

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Source: PRIA, https://policyrisk.com/federal-register/2025-19990 (as of 2026-06-08).