Description
This document provides guidance for industry on the chemistry, manufacturing, and controls (CMC) documentation that should be submitted in new drug applications (NDAs) and abbreviated new drug applications (ANDAs) for nasal spray and inhalation solution, suspension, and spray drug products intended for local and/or systemic effect. This guidance covers CMC information recommended for inclusion in the application regarding the drug product components, manufacturing process, and associated controls for each of these areas, but does not address the manufacture of drug substances. The guidance also provides recommendations on labeling. This guidance does not address propellant-based inhalation and nasal aerosols (also known as oral and nasal metereddose inhalers, MDIs), inhalation powders (also known as dry powder inhalers, DPIs), and nasal powders.
Scope & Applicability
Product Classes
10Guidance covers CMC documentation for nasal spray drug products.; Drug products containing active ingredients dissolved or suspended in solutions delivered in nonpressurized dispensers.; drug products requiring specific characterization and controls; stability information for nasal spray drug products; Guidance covers chemistry, manufacturing, and controls for nasal spray products.; labeling considerations for nasal spray drug products; Drug products intended for use by nasal inhalation.
Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
vary widely in design and mode of operation
Test parameters recommended for inhalation solution, suspension, and spray drug products
Test parameters recommended for inhalation solution, suspension, and spray drug products
Test parameters recommended for inhalation solution, suspension, and spray drug products
Table 3: Nasal Sprays
Guidance covers CMC documentation for inhalation solution drug products.; Aqueous-based formulations intended for delivery to the lungs by oral inhalation.; oral inhalation drug products requiring thorough characterization; stability information for inhalation solution drug products; Guidance covers characterization studies for inhalation solution products.; labeling considerations for inhalation solution drug products; Drug products intended for use by oral inhalation with a specified nebulizer
Guidance covers CMC documentation for inhalation suspension drug products.; Aqueous-based formulations that must be sterile and are used with a specified nebulizer.; stability information for inhalation suspension drug products; Guidance covers characterization studies for inhalation suspension products.; labeling considerations for inhalation suspension drug products; Drug products containing active ingredients suspended in a formulation for oral inhalation.
Guidance covers CMC documentation for inhalation spray drug products.; Aqueous-based drug products that do not contain any propellant and must be sterile.; stability information for inhalation spray drug products; Guidance covers characterization studies for inhalation spray products.; labeling considerations for inhalation spray drug products
Stakeholders
4Entity that owns and maintains a Drug Master File
Facility supplying raw materials or ingredients; Facility providing raw materials to a manufacturer
proper performance of the pump should be ensured primarily by the pump manufacturer
used to establish reliability of test results
Regulatory Context
Attributes
10physicochemical property affected by micronization
Excess theoretical deliverable volume to ensure transfer of declared dose.
Fill weight to be stated on the label
Property of a device that may be changed via established protocols
variation in flow rate for chromatography
Comparative performance of devices at various dosing orientations.
Determined by the sponsor for the investigational product.; investigational product(s) are stable over the period of use and only used within the current shelf life
formulation characteristic affecting pump performance
Physicochemical characteristic used to assure product acceptability.
Acceptance criteria expressed in terms of GSD
Identified Hazards
Hazards
2prior knowledge from product development, e.g., on leachables
Sponsor should also provide a safety evaluation of any extractables
Related CFR Sections (7)
- 21CFR314.3§ 314.3 Definitions.
(a) The definitions and interpretations contained in section 201 of the Federal Food, Drug, and Cosmetic Act apply to those terms when used in this part and part 320 of this chapter .Read full regulation →
- 21CFR210.3§ 210.3 Definitions.
(a) The definitions and interpretations contained in section 201 of the act shall be applicable to such terms when used in this part and in parts 211 , 225 , and 226 of this chapter .Read full regulation →
- 21CFR201.10§ 201.10 Drugs; statement of ingredients.
(a) The ingredient information required by section 502(e) of the Federal Food, Drug, and Cosmetic Act shall appear together, without any intervening written, printed, or graphic matter, except the proprietary names of ingredients, which may be included with the listing of established names, and suchRead 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 →
- 21CFR314.420§ 314.420 Drug master files.
(a) A drug master file is a submission of information to the Food and Drug Administration by a person (the drug master file holder) who intends it to be used for one of the following purposes: To permit the holder to incorporate the information by reference when the holder submits an investigationalRead full regulation →
- 21CFR200.51§ 200.51 Aqueous-based drug products for oral inhalation.
(a) All aqueous-based drug products for oral inhalation must be manufactured to be sterile.Read full regulation →
- 21CFR211.84§ 211.84 Testing and approval or rejection of components, drug product containers, and closures.
(a) Each lot of components, drug product containers, and closures shall be withheld from use until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit.Read full regulation →
Related Warning Letters (10)
- 2025-05-20
CGMP/Finished Pharmaceuticals/Adulterated
NWL Netherlands Services B.V.
- 2025-03-25
CGMP/Finished Pharmaceutical/API/Adulterated
Yangzhou Sion Commodity Co., Ltd.
- 2024-11-26
CGMP/Finished Pharmaceuticals/Adulterated
Catwalk Cosmetic Laboratories Pty Ltd.
- 2024-11-26
CGMP/Finished Pharmaceuticals/Adulterated
Hangzhou Huiji Biotechnology Co., Ltd.
- 2024-10-29
CGMP/Finished Pharmaceuticals/Adulterated
MedOffice Saglik Endustri Anonim Sirketi
- 2024-09-10
CGMP/Finished Pharmaceuticals/Adulterated
Avaria Health & Beauty Corp.
- 2024-02-06
CGMP/Finished Pharmaceuticals/Adulterated
Les Importations Herbasanté Inc.
- 2023-11-21
CGMP/Finished Pharmaceuticals/Adulterated
AmLion Toothpaste Mfg. Sdn. Bhd.
- 2023-09-05
CGMP/Finished Pharmaceuticals/Adulterated
Lex Inc.
- 2023-04-25
CGMP/Finished Pharmaceuticals/Adulterated
Pharmaplast S.A.E.
See Also (8)
- Quantitative Labeling of Sodium, Potassium, and Phosphorus for Human Over-the-Counter and Prescription Drug Products (Status: Draft)
- Formas posológicas orales sólidas de liberación inmediata Cambios de escala y posteriores a la aprobación: documentación química, de fabricación y controles, de pruebas de disolución in vitro y bioequivalencia in vivo. (Status: Final)
- SUPAC-IR: Immediate-Release Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation (Status: Final)
- SUPAC-SS: Nonsterile Semisolid Dosage Forms; Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation: Guidance for Industry (Status: Final)
- Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations (Status: Final)
- SUPAC-MR: Modified Release Solid Oral Dosage Forms Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation: Guidance for Industry (Status: Final)
- Environmental Assessment of Human Drug and Biologics Applications: Guidance for Industry (Status: Final)
- Drug Master Files for Bulk Antibiotic Drug Substances: Guidance for Industry (Status: Final)