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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This is a draft guidance. Not for implementation.

  1. Develop comprehensive in vitro testing protocol considering drug product characteristics and intended tube types
  2. Conduct required in vitro testing:
    • Recovery testing
    • Sedimentation and redispersibility
    • Stability testing
    • Additional tests as needed (particle size, acid resistance, dissolution)
  3. Document testing conditions, protocols and results in standardized format
  4. Develop detailed administration instructions based on successful testing results
  5. Prepare appropriate labeling content including:
    • Specific tube requirements
    • Preparation instructions
    • Administration procedures
    • Storage conditions
    • Warnings/contraindications if applicable
  6. Submit complete test reports and proposed labeling in application
  7. Consider early communication with FDA for guidance on testing approach
  8. For ANDAs, ensure testing demonstrates equivalence to RLD when administered via enteral tube
  9. 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

  • 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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