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Mariah NelsonParticipantI have to give an extended answer because it would be both a YES and a NO in this case and also be dependent on the specific brand or generic the study is performed with, and the regulatory environment where you operate. I hope I can provide you enough direction to help support the longer dating I am giving you in the stability study.
TERMINOLOGY:BUD = beyond use date (relates to microbial growth risk)Stability = based on the physical and chemical characteristicsPACKAGE INSERTS: these are often never updated after marketing of the product, and many times I have experienced the stability as listed to be short, or very commonly “6 hours” which sounds a lot like a USP 797 single dose vial BUD. I have also seen very specific language in package inserts that read “stability was demonstrated to 24 hours” which (to me) means they only conducted a 24 hour study, and would have been beneficial if they kept it going for 48, 72, 96 hours or longer. I have also seen many without any stability recommendations other than to “use immediately”.POST MARKETING STUDIES: as is the case with many drugs, there are post marketing studies, and you have to choose wisely what you will use in your review to settle on an appropriate stability for your organization. Many times these post marketing studies are very helpful and are found in the resources by Trissel and references in many other tertiary references such as Lexi-Comp, Micromedex, GlobalRPh, etc. Sometimes the study does not mach your preparation and you have to avoid using it.PIPERACILLIN-TAZOSINSPECIFICS: in the market there exists many generics and the brands ZOSYN and TAZOSYN, both are piparazillin-tazobactam but in this specific drug combination there are some differences across generics, most importantly is the inclusion of the excipient EDTA which is acting as a stabilizer in that it helps the drug be compatible with calcium containing solutions. If the formula does NOT contain EDTA then it will NOT be compatible with lactated ringers. In your package insert provided I can see it does contain EDTA and is also the branded TAZOSYN. I was able to find a stability study (attached) for you with very good stability results using TAZOSYN and by the some company that you are using, and this stability is also recognized in the major references as well (so it is not an outlier). The study used HPLC at multiple time points in different solutions and concentrations, and also reviewed other solution characteristics including color and pH. TAZOSYN was stable 28 days refrigerated (protected from light) and 72 hours room temperature (exposed to light). But remember USP 797 BUD limits of 30 hours room temp and 9 days refrigerated if batching under medium risk USP 797 v2008. If this was USP 797 v2019 then you cannot get the max 4 days room temp as that is longer than stability 72 hours, but you could use 10 days refrigerated. USP 797 v2019 was suspended for specific reasons that did not include these BUDs and I have seen multiple places already implement them. MANUFACTURER vs STABILITY STUDY (regulatory issues): these are often tricky to reconcile depending the area and attitudes of the regulators. I like to say “the drug is the drug is the drug” and (baring any major excipients) that is true. Manufacturers often spend a lot more time on clinical data and there is not much attention paid to stability studies, until scientists follow up with them later. It will depend on your regulatory agencies and inspectors of course, but if they are accepting of USP standards, principles of establishing expiration dates, and understanding extended stability studies, then you have what you need. You should always be reviewing the studies and having them on file to show evidence of your review. Document everything in your master formula with the references and this should be enough to use the stability longer compared to the labeling of the manufacturer. -
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