Beyond use dating (BUD) is a bit of a hassle in acute care practice. The reason is that regulatory bodies have muddied the water with information that isn’t always the most recent or evidence based.Â ISMP recently published information from a survey of 715 pharmacy professionals on drug storage, stability, and beyond use dating of injectable drugs, and the results are a bitÂ disappointing. There’s clearly a lot of confusion out there, in addition to aÂ plethoraÂ of different practice models.
For me the reference of choice for stability, storage and compatibility was always theÂ Handbook on Injectable Drugs, now in its 16th Edition. This reference was affectionately known as “Trissel’s” because the author of the book Lawrence A. TrisselÂ is a legend in the field of injectable drugs. After Trissel’s I’d do a literature search to see if I could find something that wasn’t in there; typically I couldn’t. And finally, if I couldn’t find it in Trissels’s or the literature, I’d look at theÂ manufacturer’s information.
Here’s some background information from the survey:
The Centers for Medicare & Medicaid Services (CMS) standard 42 CFR Â§482.25(b)(3) states that â€œOutdated, mislabeled, or otherwise unusable drugs and biologicals must not be available for patient use.â€ To avoid the use of outdated drugs, CMS requires pharmacists to follow the manufacturerâ€™s directions regarding storage, stability, and beyond use dating in the official US Food and Drug Administration (FDA)-approved prescribing information (package insert) [Â§482.25(a)]. The Joint Commission follows guidance from CMS on this issue, and surveyors from both agencies have cited organizations for not following the explicit directions in the manufacturerâ€™s package insert when it comes to drug storage, stability, and beyond use dating.
Only following the manufacturerâ€™s directions for injectable medications has proven difficult and wasteful in some situations for two primary reasons: 1) complete information on storage, stability, compatibility, and beyond use dating is often not provided in the official prescribing information, and 2) newer, evidence-based information on these matters can sometimes be found in peer reviewed journals and compendia fully endorsed by national pharmacy organizations. These compendia, which are widely used by pharmacists and drug information vendors, include the American Hospital Formulary Service (AHFS) Drug Information, Trisselâ€™s 2 Clinical Pharmaceutics Database (electronic), Trisselâ€™s Handbook on Injectable Drugs, and the King Guide to Parenteral Admixtures. Pharmacists should be able to use evidence-based criteria from the compendia and peer reviewed journals as long as they conform to sterility standards published in the United States Pharmacopeia (USP) Chapter <797>.
If information on storage, stability, and beyond use dating is not available in the manufacturerâ€™s directions, CMS and The Joint Commission defer to recommendations available through nationally recognized sources. But CMS is confronted with a dilemma if the official, FDA-approved manufacturerâ€™s directions differ from newer, evidence-based recommendations in national compendia. CMS is reviewing this matter further. We are hoping the results of our survey, as described below, provide CMS with some baseline information to support its review process.
Confused? You’re not alone.
The survey results are presented at the ISMP site, and I would encourage you to read them in their entirety, but they’re too long to post here. One thing is certain, the results of the survey paint a picture of confusion and practice models that couldn’t be more different. It’s clear to me that the IV room is a place where standards are needed, and I don’t mean those proposed by government agencies.
Two major issues associated with bad information on stability, storage and beyond-use-dating are waste (cost) and safety. From the survey:
Sixty-one percent of respondents said they feel compelled to discard injectable medications according to the package insert, knowing it differs from information in national compendia. These respondents collectively reported more than 100 different medications that they felt compelled to discard despite newer evidence that extends the stability and beyond use dating or alters the storage, dilution, or compatibility directions documented in the package inserts. …More than 80% of all the medications reported by respondents have been or are currently in short supply, further contributing to the alarming drug shortages in our country.
Bortezomib is one example. Once reconstituted, the manufacturer recommends use within 8 hours. Newer evidence suggests that 1 mg/mL solutions may be stored at room temperature for 3 days or under refrigeration for 5 days in a vial or syringe (Andre P, Cisternino S, Chiadmi F, et al. Stability of bortezomib 1-mg/mL solution in plastic syringe and glass vial. Ann Pharmacother. 2005;39(9):1462-6). Respondents reported that a single 3.5 mg vial of bortezomib costs $1,500-$2,500. With a typical dose of 1.3 mg/m2, unused portions of drug in these vials may be discarded unnecessarily.
A serious medication safety issue was also mentioned by respondents. If the manufacturerâ€™s directions call for very short stability and beyond use dating once the drug has been diluted for infusion, some pharmacists are not mixing the drugs in the pharmacy and are instead relying on nurses in clinical areas to perform the admixture. If more liberal beyond use dating was allowed, as recommended in national compendia, nurses may not be required to prepare infusions, even if pharmacies are not open 24 hours each day. Sterility and mixing accuracy are often compromised when admixture occurs on patient care units, and an important nurse-pharmacist independent check is lost.