FDA Guides Waivers for pH Tweaks in Eye and Ear Drugs
Published Date: 11/17/2025
Notice
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.
Analyzed Economic Effects
4 provisions identified: 4 benefits, 0 costs, 0 mixed.
How to Request pH Adjuster Waivers
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 describes the types of information applicants should consider submitting and the recommended format and process for submitting such waiver requests.
FDA Feedback Recommended Before Filing
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 formulation that contains a Q1 or Q2 pH adjuster difference.
Confidentiality of Formulation Questions Clarified
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 formulations.
Guidance Finalized and Published
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, 2022.
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