Information for Health Care Facilities and Providers on “in-use time”
FDA is aware that some health care facilities and providers are facing challenges in maintaining adequate supplies of certain drugs needed to treat patients with COVID-19. In particular, health care facilities and providers have reported that care of ventilated patients can be complicated by the need to discard containers of medications before they are fully administered because of the in-use time specified on the FDA-approved label. The “in-use time” is the maximum amount of time that can be allowed to elapse between penetration of a container-closure system containing a sterile drug product, or after a lyophilized drug product has been reconstituted, and before patient administration. 1 Some facilities and providers have indicated that they are considering use of certain drugs, for which supplies may not be consistently available, beyond the labeled “in-use times.”
- In particular, the Agency is aware that health care facilities and providers have in some cases considered use beyond the in-use time in the FDA-approved labeling for the following drugs:
- Cisatracurium besylate EQ 2 mg base/mL, EQ 10 mg base/mL
- Phenylephrine hydrochloride 0.1 mg/mL, 10 mg/mL (10 mg/mL), 50mg/5mL (10 mg/mL), 100 mg/10mL (10 mg/mL)
- Bumetanide 0.25 mg/mL
- Midazolam hydrochloride EQ 1 mg base/mL, EQ 5 mg base/mL
- Succinylcholine chloride 20 mg/mL
- Famotidine 10 mg/mL
- Hydromorphone 0.2 mg/mL, 1 mg/mL, 2 mg/mL, 4 mg/mL, 10 mg/mL
- Rocuronium bromide 50 mg/5 mL (10 mg/mL), 100 mg/10mL (10 mg/mL)
- Epinephrine EQ 1mg base/mL (EQ 1 mg base/mL) and EQ 30 mg base/mL (EQ 1 mg base/mL)
- Heparin sodium 1,000 units/mL, 5,000 units/mL, 10,000 units/mL (NDCs: 0069-0058-01, 0069-0059-01, 0069-0059-03, 0069-0137-03, 0069-0043-01)
- When an injectable drug product is prepared for administration per labeling instructions, and where FDA-approved labeling describes an in-use time for that drug product, the Agency has not necessarily evaluated data to support a longer in-use time. Use of these drug products beyond the labeled in-use times can raise important concerns related to product safety.
- Therefore, the Agency is providing the following information to minimize the likelihood of physicochemical degradation or microbial proliferation during use in situations where a provider is considering use beyond the labeled in-use time for the above-listed products. If there is a need to use these products beyond the labeled in-use time to help ensure access to the drug for patients, it is important that this period be as short as possible, and for a maximum of:
- four (4) hours for a refrigerated storage condition (if any), or
- two (2) hours for any labeled room temperature in-use time (if any)
for the specific drugs listed above.
This extended use applies to either the refrigerated or the room temperature in-use storage condition and not both storage conditions even if both refrigerated and room temperature in-use life times are provided in the labeling.
Information for Drug Manufacturers
- Application holders who wish to extend the in-use time described in their FDA-approved drug labeling should submit a supplement to their application(s). Questions about the appropriate supplement type or data to be included may be sent to CDER-OPQ-Inquiries@fda.hhs.gov.
Requests for Information
- If you are a health care facility or health care provider seeking information on the potential to use beyond the labeled in-use time a specific FDA-approved drug for injection for which you are having supply issues and that is critical for use in COVID-19 patients, where the FDA-approved labeling includes instructions for “in-use” time, please email the following to CDER-OPQ-Inquiries@fda.hhs.gov.
- the established name and strength of the FDA-approved drug
- the labeled length of time the drug can be used once the container is breached (labeled “in-use” time)
- The agency will evaluate submissions as quickly as possible and provide available information to the requestor, as appropriate.
- 1. The “in-use time” may be described in various ways in the labeling. For example, the labeling may state how long the product can be stored after dilution or reconstitution or a time within which the open product is to be used.