Description
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 This guidance finalizes the draft guidance of the same title issued on April 14, 2022.
Scope & Applicability
Product Classes
6Drug products referencing a reference listed drug; Proposed products seeking approval via ANDA.
The drug product identified by the applicant for comparison; Comparison of ANDA product to RLD for pH adjuster differences
Injectable products subject to specific inactive ingredient rules.
Eye products subject to specific inactive ingredient rules.
Ear products subject to specific inactive ingredient rules.
Reference Listed Drug used as the basis for an ANDA submission.
Stakeholders
1Entity submitting development data and knowledge; Entity performing the work process for change
Regulatory Context
Attributes
8Difference in the type of inactive ingredients
Qualitative or quantitative difference in inactive ingredients
Difference in the concentration of inactive ingredients
Qualitative difference in inactive ingredients.
Quantitative difference in inactive ingredients.
Amount as much as necessary (q.s.) to achieve a target.
Physicochemical characteristic used to assure product acceptability.
Physicochemical characteristic used to assure product acceptability.
Identified Hazards
Hazards
1Potential safety concern arising from different pH adjusters.
Related CFR Sections (7)
- 21CFR314.99§ 314.99 Other responsibilities of an applicant of an ANDA.
(a) An applicant must comply with the requirements of § 314.65 regarding withdrawal by the applicant of an unapproved ANDA and § 314.72 regarding a change in ownership of an ANDA.Read full regulation →
- 21CFR320.24§ 320.24 Types of evidence to measure bioavailability or establish bioequivalence.
(a) Bioavailability may be measured or bioequivalence may be demonstrated by several in vivo and in vitro methods. FDA may require in vivo or in vitro testing, or both, to measure the bioavailability of a drug product or establish the bioequivalence of specific drug products. Information on bioequivRead full regulation →
- 21CFR320.22§ 320.22 Criteria for waiver of evidence of in vivo bioavailability or bioequivalence.
(a) Any person submitting a full or abbreviated new drug application, or a supplemental application proposing any of the changes set forth in § 320.21(c) , may request FDA to waive the requirement for the submission of evidence measuring the in vivo bioavailability or demonstrating the in vivo bioeqRead full regulation →
- 21CFR314.94§ 314.94 Content and format of an ANDA.
ANDAs are required to be submitted in the form and contain the information required under this section. Three copies of the ANDA are required, an archival copy, a review copy, and a field copy. FDA will maintain guidance documents on the format and content of ANDAs to assist applicants in their prepRead full regulation →
- 21CFR314.127§ 314.127 Refusal to approve an ANDA.
(a) FDA will refuse to approve an ANDA for a new drug under section 505(j) of the Federal Food, Drug, and Cosmetic Act for any of the following reasons, unless the requirement has been waived under § 314.99 :Read full regulation →
- 21CFR201.100§ 201.100 Prescription drugs for human use.
A drug subject to the requirements of section 503(b)(1) of the act shall be exempt from section 502(f)(1) if all the following conditions are met:Read full regulation →
- 21CFR314.90§ 314.90 Waivers.
(a) An applicant may ask the Food and Drug Administration to waive under this section any requirement that applies to the applicant under §§ 314.50 through 314.81 . An applicant may ask FDA to waive under § 314.126(c) any criteria of an adequate and well-controlled study described in § 314.126(b) . Read full regulation →
Related Warning Letters (5)
- 2025-01-28
Unapproved New Drugs/Misbranded
Mihon Corp. d/b/a VitalityVita and Boulla, LLC
- 2023-12-26
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
East Fork Cultivars
- 2023-03-14
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
ElectRx and Health Solutions, LLC
- 2023-01-17
Finished Pharmaceuticals/Unapproved New Drug/Misbranded
HIS Enterprise Inc dba Adam’s Secret USA, LLC
- 2020-01-28
Unapproved New Drugs/Misbranded
Wave Miami LLC
See Also (8)
- Good ANDA Submission Practices Guidance for Industry (Status: Final)
- Final In Vivo Bioavailability-Bioequivalence Studies- Analytical (Status: Final)
- Topical Dermatologic Corticosteroids: in Vivo Bioequivalence (Status: Final)
- Bioresearch Monitoring Technical Conformance Guide (Status: Final)
- Data Integrity for In Vivo Bioavailability and Bioequivalence Studies (Status: Draft)
- Fixed-Combinations and Single-Entity Versions of Previously Approved Antiretrovirals for the Treatment or Prevention of Human Immunodeficiency Virus-One Under the President’s Emergency Plan for Acquired Immunodeficiency Syndrome Relief (Status: Draft)
- CVM GFI #171 - Demonstrating Bioequivalence for Soluble Powder Oral Dosage Form Products and Type A Medicated Articles Containing Active Pharmaceutical Ingredients Considered to Be Soluble in Aqueous Media (Status: Final)
- Statistical Approaches to Establishing Bioequivalence (Status: Draft)