Description
This guidance is intended to assist applicants who are submitting abbreviated new drug applications (ANDAs) for liquid-based and/or other semisolid products applied to the skin, including integumentary and mucosal (e.g., vaginal) membranes, which are hereinafter calledtopical products.2Because of the complex route of delivery associated with these products, which are typically locally acting, and the potential complexity of certain formulations, topical products (other than topical solutions) are classified as complex products.3This guidance provides recommendations for in vitro release test (IVRT) studies that can be used to compare a proposed generic (test) topical product and its reference standard (RS) for the purpose of supporting a demonstration of bioequivalence (BE) to the reference listed drug (RLD). The reference standard ordinarily is the RLD.4
Scope & Applicability
Product Classes
3Subject of the guidance, including liquid-based and semisolid products applied to skin or membranes.; Subject of the characterization guidance for ANDAs
Products with complex active ingredients or formulations
Reference Listed Drug used as the basis for an ANDA submission.
Stakeholders
4The listed drug identified by FDA upon which an applicant relies for ANDA approval.
QC personnel responsibilities within the quality management system
QA personnel responsibilities within the quality management system
The specific drug product used by the applicant for bioequivalence testing.
Regulatory Context
Attributes
8Validation parameter for IVRT method
Risk factor to be assessed during manufacturing changes
Minimum linearity requirement for IVRT specificity.
Validation parameter for IVRT method
Evaluation of robustness and parameter ranges of analytical procedures; Development of a robust multivariate analytical procedure includes scientifically justified sample selection; Capacity of an analytical procedure to meet performance criteria during normal use.; Assessed using retention time models; Performance characteristic to be validated
Linearity of drug release over time
Critical parameter typically 32°C ± 1°C
Recovery of released drug in the receptor solution should be characterized; typically less than 30%.
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 →
- 21CFR320.36§ 320.36 Requirements for maintenance of records of bioequivalence testing.
(a) All records of in vivo or in vitro tests conducted on any marketed batch of a drug product to assure that the product meets a bioequivalence requirement shall be maintained by the manufacturer for at least 2 years after the expiration date of the batch and submitted to the Food and Drug AdministRead full regulation →
- 21CFR320.63§ 320.63 Retention of bioequivalence samples.
The applicant of an abbreviated application or a supplemental application submitted under section 505 of the Federal Food, Drug, and Cosmetic Act, or, if bioequivalence testing was performed under contract, the contract research organization shall retain reserve samples of any test article and referRead full regulation →
- 21CFR320.38§ 320.38 Retention of bioavailability samples.
(a) The applicant of an application or supplemental application submitted under section 505 of the Federal Food, Drug, and Cosmetic Act, or, if bioavailability testing was performed under contract, the contract research organization shall retain an appropriately identified reserve sample of the drugRead 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 →
- 21CFR10.115§ 10.115 Good guidance practices.
(a) What are good guidance practices? Good guidance practices (GGP's) are FDA's policies and procedures for developing, issuing, and using guidance documents.Read full regulation →
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)