Oral Drug Products Administered via Enteral Feeding Tube: In Vitro Testing and Labeling Recommendations; Draft Guidance for Industry; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice of availability.

SUMMARY:

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Oral Drug Products Administered Via Enteral Feeding Tube: In Vitro Testing and Labeling Recommendations.” This draft guidance provides recommendations for consistent in vitro testing of oral drug products to demonstrate their suitability to be administered via enteral tube. In addition, it supports the development of clear product-specific enteral tube administration instructions in labeling for administration to patients unable to ingest oral drug products.

DATES:

Submit either electronic or written comments on the draft guidance by August 2, 2021 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.

ADDRESSES:

You may submit comments on any guidance at any time as follows:

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov . Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov .
• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

• Mail/Hand Delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2021-D-0391 for “Oral Drug Products Administered Via Enteral Feeding Tube: In Vitro Testing and Labeling Recommendations.” Received comments will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

• Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov . Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf .

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.

You may submit comments on any guidance at any time (see 21 CFR 10.115(g)(5)).

Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002, or Office of Policy, Guidance and Policy Development, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5431, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:

Amy Muhlberg, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg., 51, Rm. 3117, Silver Spring, MD 20993-0002, 240-402-6901; or Shanil Haugen, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg., 66, Rm. 2612, Silver Spring, MD 20993-0002, 301-796-0301.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry entitled “Oral Drug Products Administered Via Enteral Feeding Tube: In Vitro Testing and Labeling Recommendations.” This 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. Specifically, the draft guidance provides recommendations for consistent in vitro testing of oral drug products to demonstrate their suitability to be administered via enteral tube. In addition, it supports the development of clear, product-specific enteral tube administration instructions in labeling for administration to patients unable to ingest oral drug products.

Enteral tubes are critical for patients who are unable to swallow oral dosage forms because of feeding disorders, severe intellectual disabilities, neurological disorders, cancers, and other medical conditions or therapies that compromise swallowing or the function of the proximal gastrointestinal system. 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.

Some FDA-approved drug products marketed in the United States include instructions for enteral tube administration in their labeling. However, testing is not sufficiently widespread or consistent, and the content and format of labeling statements regarding administration of drug products via enteral tube vary.

The Agency recognizes the need for consistent in vitro testing to ensure safe and effective delivery of drugs that may be administered via enteral tube and to identify drugs that cannot be administered through an enteral tube without altering the safety and effectiveness profile of the drug product or compromising the integrity of the tube.

The draft guidance covers selection of appropriate enteral tubes for testing, selection of the dispersion media and preparation of the drug dispersion, and testing conditions and methods. Additional recommendations are given for modified release drug products. Completion of the recommended testing of a drug product prepared in the same manner as it will be prepared for administration to a patient in the clinical setting should allow applicants to demonstrate whether a drug product is suitable for enteral tube administration and identify drug products that are incompatible with enteral tube administration.

Finally, the draft guidance covers how to summarize information regarding administration of the drug product via enteral tube in labeling, including example labeling statements for drug products that can be safely and effectively administered via enteral tube and labeling statements for drug products that are not recommended for administration via enteral tube.

FDA requests comment from the public regarding the extent to which the recommendations in the guidance could be applicable to nonprescription products marketed under over-the-counter monographs that could be administered via enteral tube.

This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the current thinking of FDA on “Oral Drug Products Administered Via Enteral Feeding Tube: In Vitro Testing and Labeling Recommendations.” It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

While this draft guidance contains no collection of information, it does refer to previously approved FDA collections of information. Therefore, clearance by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521) is not required for this draft guidance. The previously approved collections of information are subject to review by OMB under the PRA. The collections of information in 21 CFR parts 312 and 314 have been approved under OMB control numbers 0910-0014 and 0910-0001, respectively. The collections of information in 21 CFR 201.56 and 201.57 have been approved under OMB control number 0910-0572.

III. Electronic Access

Persons with access to the internet may obtain the draft guidance at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs,, https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-and-radiation-emitting-products,, or https://www.regulations.gov .