Anthony Grzib, R.Ph, Vice President, Pharmacy Quality
Unraveling the recent changes to the Beyond-Use Dates of compounded medications
By now you’ve likely heard about and may be experiencing some of the frustration and confusion surrounding recent changes to the shelf life, also known as the Beyond-Use Date (BUD), of some compounded medication. You may be asking what these changes are, why they happened, why they affect only some of your compounded medications but not others, and what you can do to manage your clients and consistently treat your patients moving forward. As your compounding partner, Wedgewood is here to help you sort through these extremely valid and important questions.
What is a Beyond-Use Date (BUD) and why have they changed?
A Beyond Use Date (BUD) for a compounded medication is similar to an expiration date given to any other drug. It is the date beyond which the use of the compounded medication is not recommended. In theory, it should be the date at which a compounded medication is no longer able to retain the same level of potency or stability it had on the day it was made. And historically, that is how compounders assigned BUDs to compounded medication; in compliance with regulatory requirements and existing United States Pharmacopeia (USP) quality standards, compounders used published stability information, known degradation profiles of active pharmaceutical ingredients, and/or direct testing of compounded medication over time to determine BUDs.
On November 1, 2023, the updated compounding quality standards published by the United States Pharmacopeia (USP) went into effect. The updated standards, created by a team of industry experts that included veterinarians and members of the FDA, included changes to how a compounder could assign a BUD to a compounded medication. Per the new USP standards, the information historically permitted to be used to assign BUDs can be used by compounders as a guide to assign BUDs, but it can no longer be used as the basis for BUD assignment. Instead, BUDs assigned to compounded medications can now only be based on either the timelines published in the revised USP or based on validated stability studies conducted on the specific compounded formula being prepared by the compounder. In the case of the latter, the new USP requirements place an upper limit on the maximum allowable BUD regardless of whether stability study data indicates the compounded medication is stable for longer.
Why am I seeing changes to only some compounds?
Several factors are currently driving the variability in BUDs of compounded medication in the marketplace.
One factor is whether or not the compound is being prepared at a facility that is complying with the new USP standards. Historically the compounding standards published in USP have been generally accepted as a set of uniform quality standards applicable to all compounding pharmacies in the country. But the standards are just that – standards. In order for them to become requirements, each state must adopt them as regulation. While most states have adopted the November 1st revisions as regulation, some have yet to do so, meaning some pharmacies in some states have chosen not to implement the revised USP standards for assigning BUDs because they are not required to do so. This is one of the reasons for the disparity in BUDs assigned to the same compounds made by different pharmacies.
Wedgewood is committed to, and has made significant investment in, ensuring all its state-licensed pharmacies meet all of the revised USP standards. While we don’t necessarily agree that some of the new USP BUD limitations improve product quality or patient safety, we do agree that the revised standards as a whole have greatly raised the bar on the quality of compounded medications. We welcome these new practices, many of which Wedgewood has had in place for years, as the national standard for compounding pharmacies. States will continue to adopt the standards as regulation, and since Wedgewood is already meeting those standards, we are well positioned to ensure no disruption in products or services that might be faced by other pharmacies who will need to make future changes to come into regulatory compliance.
The other factors that are causing what likely seems like random variations in BUDs assigned to compounded medications have to do with the USP BUD standards themselves. For nonsterile compounds, USP has established essentially four categories of maximum BUDs, ranging from 14 days to 180 days, that can be assigned to a compounded medication based on the type of ingredients used in the formula for that medication. A compounder can extend the BUD of a nonsterile compounded medication beyond these maximums, up to a limit of 180 days, if validated stability studies are performed on the specific compound. However, the cost of performing these studies starts at roughly $40,000 per compound, and each study can only be applied to a narrow set of compounded items that share the same ingredients, compounding steps, and finished packaging. This narrow applicability of stability study information can cause significant differences in BUDs for nonsterile compounds that essentially seem to be the same. For example, a preserved, aqueous-based oral liquid compound supplied in a four-ounce bottle that’s undergone a stability study can have data from that study supporting a 180-day BUD, but that same preserved aqueous-based oral liquid supplied in an eight-ounce bottle that wasn’t part of the stability study could only be assigned a 35-day BUD.
For sterile compounds, the USP BUD standards become even more varied, with the maximum allowable BUDs based on a matrix of different factors, including the source of starting ingredients, environmental conditions under which the compound is prepared, the level of environmental monitoring and personnel training in place, sterilization method used, and storage conditions of the finished sterile compound. While USP allows compounders to utilize validated stability studies to extend the BUDs of sterile compounds, these extensions are limited to 60 to 180 days according to a similar matrix of factors even if a validated stability study scientifically shows the compounded preparation is stable for much longer.
Lastly, the USP compounding standards are not applicable to medications produced by 503B outsourcing facilities, like Wedgewood Connect, meaning these facilities can assign longer BUDs to their products because they follow a different set of practice standards created and enforced by the FDA called current Good Manufacturing Practices (cGMP).
What should I expect moving forward and how do I manage patient treatment?
Wedgewood, and likely other pharmacies that you work with, have invested significant time, effort, and money in navigating through the complexities of these new USP BUD standards in order to take the necessary steps to assign the maximum allowable BUDs to compounded medication while at the same time minimizing any significant price increases. These steps include:
- Investing millions of dollars into stability study testing to extend the BUDs of common items.
- Consolidating items into fewer dosage forms, strengths, or package sizes to minimize the price impact of stability study costs.
- Converting water-based formulas to oil-based or anhydrous formulas.
- Discontinuing water-based formula items that cannot be tested or shifted to oil or anhydrous.
- Changing the storage conditions of sterile items to refrigerated or frozen.
- Transferring the compounding of items, especially sterile items, to 503B outsourcing facilities.
- Discontinuing sterile items that cannot be assigned a BUD longer than the time it takes to conduct a sterility test (typically 18-22 days).
While Wedgewood and other compounders committed to compliance with USP standards will continue taking steps to assign the longest allowable BUDs to as many of their compounds as possible, the new USP standards have created an industry-wide shift of shorter BUDs being assigned to compounds, most significantly with sterile compounds. For compounders, shorter BUDs mean having to make smaller amounts of compounds more often; essentially doing two to three times the amount of work to provide you and your clients with the same amount of medication. For you, shorter BUDs mean more frequent ordering of smaller amounts or package sizes, which is why Wedgewood is investing in new tools to make ordering easier to minimize the efficiency and costs impacts this is having on you.
As no pharmacy will ever be able to perform the stability studies necessary to assign the maximum allowable BUD on every item they compound, we encourage you to take the following steps to minimize confusion and frustration you and your clients may be currently experiencing:
- Pay close attention to the BUDs of compounds when you are ordering historical quantities – you may need to adjust these quantities to avoid compounds expiring before they are completely used or consumed.
- Look at alternatives for common dosage forms, strengths, or packages sizes – it is possible there is a similar medication available with a much longer BUD than the one you historically order.
- Update the frequency of reviewing the BUDs of medications you keep in stock to ensure there is no expired medication on your shelf.
- Encourage your clients to set up AutoRefill when they pay for their first prescription to help them manage the more frequent refills that may be needed to ensure continued medication compliance.
Our commitment to you and your patients includes a commitment to continually meet the highest quality standards in the industry, and the new USP standards that took effect on November 1st are those highest quality standards. Unfortunately, the practical implications of a small section of those standards related to BUDs has created some obstacles to compounders’ ability to provide you and your clients with the breadth and quantity of medication that you’re used to. Rest assured that Wedgewood will continue to partner with you in ensuring that you and your patients receive the highest quality compounded medication that best fits your needs.