In Vitro Testing and Labeling for Oral Drug Products Administered via Enteral Feeding Tubes (DRAFT)
This guidance provides recommendations for in vitro testing and labeling of oral drug products (except solutions) that are administered via enteral feeding tubes. It applies to NDAs and ANDAs where applicants seek enteral tube administration instructions in labeling. The guidance focuses on ensuring drug product quality and bioequivalence when evaluating suitability for enteral tube administration.
This is a draft guidance. Not for implementation.
Recommended Actions
- Develop comprehensive in vitro testing protocol considering drug product characteristics and intended tube types
- Conduct required in vitro testing:
- Recovery testing
- Sedimentation and redispersibility
- Stability testing
- Additional tests as needed (particle size, acid resistance, dissolution)
- Document testing conditions, protocols and results in standardized format
- Develop detailed administration instructions based on successful testing results
- Prepare appropriate labeling content including:
- Specific tube requirements
- Preparation instructions
- Administration procedures
- Storage conditions
- Warnings/contraindications if applicable
- Submit complete test reports and proposed labeling in application
- Consider early communication with FDA for guidance on testing approach
- For ANDAs, ensure testing demonstrates equivalence to RLD when administered via enteral tube
- Maintain documentation of test results and justification for specifications
Key Considerations
Non-clinical testing
- Recovery testing to determine percentage of drug dose passing through tube
- Sedimentation volume and redispersibility testing
- In-use stability testing in dispersion media
- Particle size distribution studies for modified-release formulations
- Acid resistance testing for enteric-coated products
- Dissolution testing for extended-release products
Labelling
- Include information on suitable dosage forms and strengths
- Specify recommended enteral tube characteristics (type, size, material)
- Provide detailed preparation and administration instructions
- Include storage instructions for residual drug product dispersion
- State if product is NOT recommended for enteral tube administration
- Cross-reference relevant information in other labeling sections
Biocompatibility
- Evaluate drug product-enteral tube material interactions
- Consider pH effects on tube material compatibility
Safety
- Assess risk of tube occlusion
- Evaluate stability during preparation and administration
- Consider microbiological testing for extended holding times
Other considerations
- Selection of appropriate dispersion media
- Development of validated analytical methods
- Documentation of testing conditions and protocols
- Statistical analysis of test results
Relevant Guidances
- Essential Drug Delivery Outputs for Drug Delivery Devices and Combination Products (Draft)
- Compliance Requirements for Ophthalmic Drug-Device Combination Products Following Genus Decision
- Early Development Considerations for Combination Products
- Human Factors Studies and Related Analyses for Combination Products
- Current Good Manufacturing Practice Requirements for Combination Products
- Premarket Review Pathways for Combination Products
- Postmarketing Safety Reporting Requirements for Combination Products
- Obtaining FDA Feedback for Combination Products: Best Practices and Meeting Procedures
- Postapproval Changes to Combination Products: Marketing Submission Requirements (Draft)
Related references and norms
- USP <1111>: Microbiological Examination of Nonsterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use
- USP <61>: Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests
- USP <62>: Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms
- USP <1151>: Pharmaceutical Dosage Forms
Original guidance
- In Vitro Testing and Labeling for Oral Drug Products Administered via Enteral Feeding Tubes
- HTML / PDF
- Issue date: 2021-06-02
- Last changed date: 2022-02-01
- Status: DRAFT
- Official FDA topics: Chemistry, Pharmaceutical Quality, Medical Devices, Manufacturing, Drugs, Labeling, and Controls (CMC)
- ReguVirta summary file ID: 6245801c932ad2dd18cc1593e262f19b
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