To see my notes on 2023 USP <797> presented at ALSHP on November 3, 2022, The Future of Sterile Compounding for Health-Systems, click the link below:
In this presentation I discussed “Bulk Compounded Solutions” and I was asked to better elaborate on this topic and to further explain what it is and how it differs from other compounded sterile products (CSPs). I also addressed this question as it came up on the January 10th live webinar with Pharmacy Starts SCXP (Sterile Compounding Expert Panel).
In my notes from the ALSHP November 3, 2022 presentation, I referenced the following chart:
I stated that a “Bulk Compounded Solution” is a CSP that is made for future use as an ingredient in another CSP or a compounded bulk medication from which individual doses will be repackaged for different patients”. (As clarification, more appropriately I should have used the exact term used in USP <797>, “Compounded Stock Solutions” and will be addressing it as such going forward).
This is a very difficult subject to explain without visuals so, to better illustrate, I will share the following flowchart that I used during the live SCXP Q&A.
In this example, a CSP, without preservative, is used as a component to prepare another CSP or to repackage into unit-of-use preparations for specific patients:
The CSP was made and given a 10-day refrigerated BUD. The CSP was stored for 2 days, leaving 8-days BUD, and was used to make/repackage a new CSP
Once altered, the component CSP assumes a new identity as a single-dose container (being without preservative)
This component CSP is reassigned a BUD of 12 hours (reflective of the BUD for a single-dose container)
The new final CSP or repackaged final CSP made from this component CSP must not exceed the original BUD of the component CSP (in this case 8 days)
Assuming that there is product left over, the BUD of additional CSPs made from this same component would continue to be limited by the original BUD of the component CSP (in this case 8 days) and notthe reassigned 12-hour BUD as a single-dose container
Only the original BUD of the component CSP is limiting to the final CSP
The reassigned BUD as a single-dose container is not intended to limit the BUD of the final CSP
There are some exceptions to this rule where the original BUD of the component CSP does NOT limit the BUD of the final CSP and useful for the compounder using API and/or those compounding Category 3 CSPs.
pH-adjusters = better stability
Terminal sterilization & sterility testing
When using a pH-adjuster, the compounder is essentially altering the chemistry of the final CSP so that it is more stable. As long as there is stability data that supports the BUD assigned when using a pH-adjuster then the original BUD of the component CSP does not limit the final CSP. The new CSP may be given a USP BUD. Additionally, terminal sterilization and sterility testing will override this limiting factor of the component CSP since sterility can be proven through testing and the new final CSP may be assigned a BUD from USP.
The concept of repackaging a CSP becomes very useful as well for certain patient populations when special dilutions are needed. USP does not directly address the repackaging of “Compounded Stock Solutions” however, if you look at USP definitions for both compounding and repackaging this intent becomes clear.
USP definitions:
Compounding: The process of combining, admixing, diluting, pooling, repackaging, or otherwise altering a drug product or bulk drug substance to create a sterile preparation
Repackaging: Repackaging of a sterile product or preparation from its original container into another container must be performed in accordance with the requirements in this chapter.
Here, we see that repackaging includes “preparations” (i.e., CSPs) and that repackaging is considered compounding. Therefore, repackaging of a CSP is considered compounding and is assigned the same BUD as if repackaging of a manufactured component. Additionally, once a CSP is altered, just as a manufactured product, it changes identity as a single-dose or multi-dose container.
Remember, that USP focuses on minimum standards, and it is impossible to define all experiences so from time to time we do need dig deep into USP to find the right answer. Ensuring that these practices are in place and understood by the compounder will keep patients safe and your IV room efficient.
Thank you for visiting my site. For more information please visit www.SoignerSolutions.com or email me directly at smilstead@SoignerUniversal.com
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