Today, the FDA released its draft guidance entitled Oral Drug Products Administered Via Enteral Feeding Tube: In Vitro Testing and Labeling Recommendations Guidance for Industry (here). There have been numerous cases of clogging or otherwise blocking of enteral naso-gastric (N-G) feeding tubes when medication is administered due to a number of different reasons: swelling of the contents of the dosage form, aggregation of the particles, and interactions with the tube itself that can cause obstruction of the tube. Obviously, such obstruction could result in either lack of dosing or incomplete dosing of the drug and the potential need to remove, clear, and/or replace the feeding tube.
According to the FDA “[T]his draft guidance provides recommendations regarding in vitro testing of oral drug products, other than solutions, administered via enteral feeding tube (hereinafter enteral tube) that are subject to: (1) new drug applications (original or supplemental) where applicants are seeking and/or revising enteral tube administration instructions and related information in labeling; (2) abbreviated new drug applications where the reference listed drug contains enteral tube administration instructions and related information in labeling; and (3) investigational new drug applications where the investigational drug product is administered or planned for administration via enteral tube.”
The guidance goes on to discuss the need to standardize in vitro testing to ensure that sufficient data is available to support the labeling of a drug product for NG tube enteral administration. Once an NDA product labeling is approved to include directions for enteral administration, it is then essential for generic copies of the medication to also perform without causing problems in this context. There is one example where the approved NDA product contained labeling for administration via an enteral feeding tube, but the ANDA product was not required to perform the in vitro evaluation. This led to the subsequent withdrawal of the ANDA product, as it was found that the formulation of the ANDA product swelled in the tube, causing blockage. This case brought awareness to the need for such in vitro testing in cases where NG tube administration is approved in the labeling of the RLD.
In addition to general testing requirements, the FDA recommends specific testing types including:
- Drug Recovery – testing to assure the required dose is delivered through the tube.
- Sedimentation Volume and Re-dispersibility Testing – to assure insoluble components do not remain to have the potential to clog the tube.
- In-Use Stability in Designated Dispersion Media – to be used when the product is prepared in dispersion and may be stored for a short period of time prior to administration to assure the dispersion media does not affect the potency of the product, or disrupt the modified or extended-release, or other important properties of the product to be administered.
- Particle Size Distribution Study – particle size distribution is an important factor in assuring the drug product passes through the enteral tube and may be a significant factor in tube clogging.
- Acid Resistance Testing for Drug Products with an Enteric Coating – this testing is necessary to assure the integrity of the enteric coating is maintained until the dose is delivered.
- Dissolution Testing for Extended-Release Drug Products – Describes and provides instructions for testing requirements of extended-release dosage forms and the attributes and characteristics including dissolution in vitro administration test that should be evaluated.
There are other recommendations as well as labeling considerations (including if the NDA product is found not to be suitable for NG tube administration) that should be addressed which are outlined in the guidance. This guidance will provide the applicant with an outline for testing to ensure their product is appropriate for enteral tube administration and provides a road map for success to include such administration instructions in approved labeling.