Single-Dose, Multiple-Dose or Single-Patient-Use Container?

Recommendation

15/16 November 2023

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Requirements, Challenges & Solutions

Unsafe injection practices, including the improper use of medication vials for more than one patient, have resulted in severe drug safety issues like, for example, bacterial infections transmitted between patients. To address confusion regarding the current container terminology, the FDA is retiring the term “single-use” and creating a new package type term “single-patient-use” container, to address the need for describing a package that contains multiple doses of an injectable medical product that is intended to be used on a single patient.

Specifically, this new guidance provides FDA’s revised definitions for single-dose and multiple-dose containers as well as for the new package type term single-patient-use container. These containers may be part of a drug, a biological product, or a combination product.

According to the guideline, the definitions for containers of a sterile medication for parenteral administration (i.e. parenteral preparations like injections or infusions) are being revised as follows:

Single-Dose Container

A single-dose container is a container of a parenteral preparation that is not required to meet the antimicrobial effectiveness testing requirements. A single-dose container is designed for use with a single patient as a single injection/ infusion. Examples of single-dose containers are vials, ampules, and prefilled syringes.

Multiple-Dose Container

A multiple-dose container is a container of a parenteral preparation that has met antimicrobial effectiveness testing requirements, or is excluded from such testing requirements by FDA regulation. It is intended to contain more than one dose of the drug product. Multiple-dose containers are generally expected to contain 30 mL or less of product. The beyond-use date for an opened or entered (e.g., needle-punctured) multiple-dose container is 28 days, unless otherwise specified by the manufacturer on the label. An example of a multiple-dose container is a vial.

Single-Patient-Use Container

A single-patient-use container is a container of a parenteral preparation that is intended to be used multiple times for a single patient. Examples of single-patient-use containers are patient controlled analgesia cartridges and certain pens for injection.

For multiple-dose and single-patient-use containers, the antimicrobial effectiveness testing results will be used to support the labeled beyond-use date or discard statements.

The agency says that "Applicants should determine the proper package type term (“single-dose,” “multiple-dose,” or “single-patient-use”) for injectable medical products for human use and use only the correct term for the package type throughout the labeling". Furthermore, the package type term “single-dose” is required to appear on the container labels of single-dose injectable medical products that have a United States Pharmacopeia (USP) monograph, when space permits. When space does not permit the “single-dose” term to appear on such products’ container labels, it must appear on the carton or other outer container or wrapper, or in the prescribing information.

Labeling changes

The agency recommends that applicants make the necessary labeling changes within two years of the publication of this guidance. All submissions should clearly identify the changes being made. In addition, a supplement submission should be identified as “Labeling Changes to Follow the Package Type Term Guidance”. For approved applications, changes made to labeling according to the new guidance should be submitted to the FDA as described below:

• For a drug product that was designed and otherwise labeled for use with a single patient as a single injection/infusion, a change from the package type term “single-use” to “single-dose” should be submitted in an annual report.
• All other changes to a package type term, including a change from the package type term “single-use” to “single-patient-use,” as well as a change from “multiple-dose” to “single-patient-use” should be submitted as a “Prior Approval Supplement” (PAS).
• Changes made to add a package type term to the container/carton labeling when no package type is included:
  - If the prescribing information already includes the appropriate (correct) package type but the container/carton labeling lacks the designation, authorization holders may submit the addition of the package type term to the container/carton labeling in an annual report. The same procedure applies if the container/carton labeling includes the appropriate (correct) package type but the prescribing information lacks the designation.
  -  If neither the container/carton labeling nor the prescribing information has a package type term listed, NDA (New Drug Application) and BLA (Biologics License Application) holders should submit a PAS to add the appropriate term to the container/carton labeling and prescribing information. After FDA approval of the PAS for the NDA RLD (reference listed drug), corresponding ANDA (Abbreviated New Drug Application) holders are required to submit conforming labeling revisions in a CBE-0 supplement. If approval of the NDA for the RLD has been withdrawn, the corresponding ANDA holders should submit a PAS to propose a package type term.
• For any other proposed changes regarding package type terms, authorization holders should contact the agency.

More information can be found in FDA´s guidance "Selection of the Appropriate Package Type Terms and Recommendations for Labeling Injectable Medical Products Packaged in Multiple-Dose, Single-Dose, and Single-Patient-Use Containers for Human Use".