Description
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Content and Format of Composition Statements in NDAs and ANDAs and Corresponding Statement of Ingredients in Labeling.” This guidance is intended to assist new drug application (NDA) and abbreviated new drug application (ANDA) applicants in submitting an accurate and complete composition statement in their applications and corresponding statement of ingredients in the labeling, when applicable. This guidance describes best practices for writing the composition statement and corresponding statement of ingredients in labeling. This guidance recommends how applicants can provide complete information with the goal of minimizing the number of assessment cycles and communications that are necessary for approval, as well as ensuring product labels are written clearly.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
1The drug product identified by the applicant for comparison; Comparison of ANDA product to RLD for pH adjuster differences
Stakeholders
1Entity submitting development data and knowledge; Entity performing the work process for change
Regulatory Context
Regulatory Activities
2New Drug Application
Abbreviated New Drug Application
Document Types
10Information submitted in a drug product's NDA or ANDA
Specific section of the Prescribing Information for ingredient listing
Reporting category for minor changes like removing a color additive
Information contained in a drug product's DESCRIPTION section of its prescribing information
The primary section of drug labeling where SLCs are implemented
Records used to ensure consistency in composition
Reports containing drug product compositions
Location of the drug product composition statement
Records in section 3.2.R that must be consistent with composition statements
A submission to FDA that may be used to provide confidential information about facilities or processes.; cross-referencing a DMF in a BLA
Attributes
7Ingredient information regarding identity
Information not required by regulation but recommended for inclusion
Functionality of sodium hydroxide in labeling
Ingredient information regarding amount
Qualitative sameness of inactive ingredients
Quantitative sameness of inactive ingredients
Property of inactive ingredients that must be identified in the application; Applicants should list the ingredients' hydration state(s)
Technical Details
Substances
10Referenced by non-combination product regulatory submissions in more than one center.
Added for in situ conversion and pH adjustment
Added to adjust pH
Inactive ingredient/vehicle listed in the example
Inactive ingredient listed in the example
Inactive ingredient listed in the example
Inactive ingredient listed in the example
Inactive ingredient listed in the example
Inactive ingredient listed in the example
Salt form equivalent of the active ingredient
Processes
2The process for which all components must be listed
composition table should indicate the amount used for in situ conversion
Standards & References
External Standards
4See USP General Chapter <1091> Labeling of Inactive Ingredients.
Official compendium for device recognition
USP General Notices 3.20, Indicating Conformance.
Standard for inactive ingredient titles and monographs; Anhydrous and dihydrate terms are consistent with USP-NF monograph terminology.
Specifications
1USP purity standard for citric acid
Related CFR Sections (9)
- 21CFR314.97§ 314.97 Supplements and other changes to an approved ANDA.
(a) General requirements. The applicant must comply with the requirements of §§ 314.70 and 314.71 regarding the submission of supplemental ANDAs and other changes to an approved ANDA.Read full regulation →
- 21CFR314.70§ 314.70 Supplements and other changes to an approved NDA.
(a) Changes to an approved NDA.Read full regulation →
- 21CFR201.57§ 201.57 Specific requirements on content and format of labeling for human prescription drug and biological products described in § 201.56(b)(1) .
The requirements in this section apply only to prescription drug products described in § 201.56(b)(1) and must be implemented according to the schedule specified in § 201.56(c) , except for the requirement in paragraph (c)(18) of this section to reprint any FDA-approved patient labeling at the end oRead full regulation →
- 21CFR201.80§ 201.80 Specific requirements on content and format of labeling for human prescription drug and biological products; older drugs not described in § 201.56(b)(1) .
Each section heading listed in § 201.56(d) , if not omitted under § 201.56(d)(3) , shall contain the following information in the following order: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 →
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead 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 →
- 21CFR320.21§ 320.21 Requirements for submission of bioavailability and bioequivalence data.
(a) Any person submitting a full new drug application to the Food and Drug Administration (FDA) shall include in the application either:Read 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 →
Enforcement Impact
Deficiencies cited in Warning Letters referencing the same regulations
Recent Cases
- 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
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)
- Labeling OTC Human Drug Products Updating Labeling in RLDs and ANDAs (Status: Final)
- PET Drug Applications - Content and Format for NDAs and ANDAs: Attachment I: Sample formats for chemistry, manufacturing, and controls (CMC) sections_2011 (Status: Final)
- Immunogenicity-Related Considerations for Low Molecular Weight Heparin Guidance for Industry (Status: Final)
- Type V DMFs for CDER-Led Combination Products Using Device Constituent Parts With Electronics or Software Guidance for Industry (Status: Draft)
- Orange Book Questions and Answers Guidance for Industry: Guidance for Industry (Status: Final)
- Changes to Disposable Manufacturing Materials: Questions and Answers Guidance for Industry (Status: Final)
- Comparability Protocols for Postapproval Changes to the Chemistry, Manufacturing, and Controls Information in an NDA, ANDA, or BLA (Status: Final)
- ANDA Submissions – Prior Approval Supplements Under GDUFA: Guidance for Industry (Status: Final)