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FDA provides draft guidance for enteral tube-administered drugs

Posted 02 June 2021 | By Kari Oakes 

FDA provides draft guidance for enteral tube-administered drugs

A new draft guidance from the US Food and Drug Administration (FDA) gives recommendations for how to test oral drug products’ suitability for enteral feeding tube administration.
 
Oral solutions are specifically excluded from the guidance, which identifies best practices for “consistent in vitro testing of oral drug products to demonstrate their suitability to be administered via enteral tube,” according to the Federal Register notice of the availability of the draft guidance.
 
Enteral tubes, or feeding tubes, may be required to maintain adequate nutrition for a host of reasons ranging from swallowing difficulty to severe genetic or acquired neurological impairment to cancer and other diseases. “It is critical that each drug administered via enteral tube is delivered at the correct dose in a manner that preserves the drug's expected safety and efficacy profile and does not compromise the integrity of the tube,” wrote FDA in its notice.
 
Currently, in vitro testing of oral drugs that might be administered via enteral feeding tube is “not sufficiently widespread or consistent,” and labeling statements vary in both content and format, noted the agency. The new draft guidance is designed to meet a need for consistent testing to identify drugs that can be administered safely and effectively via enteral tube without adversely affecting the tube’s integrity, as well as those that do not meet these criteria.
 
The draft guidance addresses in vitro testing development considerations, including a recommendation to select the smallest intended enteral tube size for each material type or tube design that the applicant intends to recommend in its labeling. Applicants should also give consideration to differing material and design types of tubes, and how these differences could affect enteral administration of the drug product. “FDA recommends that applicants test at least three different enteral tube configurations for all tube types proposed in the labeling and provide justification for the enteral tubes selected for testing,” according to the draft guidance.
 
Applicants should consider the range of dispersion media that are used for enteral drug administration. The guidance recommends taking into account factors such as the volume, temperature and pH of the medium, holding and soaking time between dispersion and drug administration, frequency and number of drug administrations, and characteristics of the tube and syringe used for administration.
 
“Development of in vitro methods should follow a risk-based process,” wrote FDA in the draft guidance. In general, the formulation that poses the highest risk of enteral tube occlusion should be selected for testing, and developers should provide a rationale for their choice. Modified-release dosage forms require additional testing considerations, since enteral tube administration may affect release characteristics of these formulations. Dissolution testing should be performed for extended-release drug products, and enteric-coated drugs require acid resistance testing.
 
The draft guidance also outlines recovery testing considerations, so applicants can report accurately on the percentage of drug recovered at the tube exit compared to the dose delivered. Video or photographic documentation of tube contents before, during and after testing should accompany the application.
 
Applicants should also plan to conduct sedimentation volume and re-dispersibility testing, and to demonstrate in-use stability in the designated dispersion media. Particle size distributions studies should also be performed using a “validated method that is sufficiently reproducible and sensitive,” such as laser diffraction, according to the guidance.
 
The guidance, which also provides recommendations for clear labeling regarding enteral tube administrations of oral drugs, applies to new drug applications, both original and supplemental, where applicants seek labeling that includes new or revised instructions for enteral tube administration. It also applies to abbreviated new drug applications where enteral tube administration information is included in the labeling for the reference listed drug, as well as to investigational new drug applications where enteral tube administration is planned.
 
Specific considerations for different application types are provided, and the guidance gives detailed labeling recommendations along with examples of instructions for preparation and administration of drugs in dispersion media via enteral tube.
 
The draft guidance is open for public consultation for 60 days from its date of publication.
 
FDA

 

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