Thank you for the opportunity to comment on document 110-36. In the new USP there are changes that will enhance compounding quality and patient safety, however there are several arbitrary changes that will not. I wanted to voice my concern on these changes relevant to the new USP along with document 110-36.
The compounding Expert Committee (CEC) of the U.S. Pharmacopeia (USP) has introduced revised chapters 795 and 797 that became effective November 1st, 2023. In several of the recommendations the CEC has not enunciated the scientific basis for the restrictions or how those restrictions keep patients safer. This is a deviation from the CEC from the norm with an independent organization like USP, whose credibility should be rooted in hard data to document the standards that it issues. These restrictions, that are not based on scientific data, create impediments to patient access to certain compounded sterile preparations.
As the state board of pharmacy, it is imperative that the board is aware and has considered all of the implications of certain unsubstantiated restrictions on patient safety and access in Virginia.
Below are proposed changes to USP that should not be implemented without thoughtful consideration of the Virginia Board of Pharmacy:
Moreover, items that I believe need clarity in document 110-36 are listed below:
USP 797 beyond-use dating, batch size restriction and increased environmental monitoring:
USP 797 restricts batch sized for compounded sterile product (CSPs) to 250 units and limits beyond-use dates of these compounds without providing evidence that the new restrictions enhance patient safety by reducing the risk of contamination. 250 units is an arbitrary batch size limit. Moreover, limiting the batch size could potentially increase contamination. With a reduced batch size compounders will now need to prepare multiple batches instead of fewer larger batches, increasing the number of manipulations and foot traffic inside sterile environments. Furthermore, increased activity may increase fatigue for the compounder and may lead to poor aseptic technique. Financially the requirement of more batches increases cost associated in preparing the medications which will ultimately result in higher costs for patients. The CEC has provided no data that the implementation of the batch size limit, which doubles the percentage of units tested per batch, will increase the probability of detecting a contaminated sample. In addition, the CEC has provided no explanation why the new guidelines restrict the batch size rather than increasing the minimum number of required samples for a batch regardless of batch size.
Another new restriction in the current USP 797 is a limit on beyond-use dating to less than 180 days with no scientific basis for the restriction. This restriction will require compounders to compound CSPs more frequently to meet patient need, increasing the number of batches. Also, shorter BUDs will mean that patients must get refills more frequently, increasing patient inconvenience and increasing the risk that a patient may not stay adherent to their drug therapy.
The CEC has acknowledged the need for CSPs to be assigned a BUD of up to 180 days but missed the mark allowing category 3 CSPs in general to be assigned a BUD of up to 180 days and instead only allows on type of category 3 CSP (terminally sterilized, stored frozen) a maximum BUD of 180 days. The need in today’s healthcare system for CSPs with extended BUDs up to 180 days goes beyond just terminally sterilized CSPs stored frozen, it is a need that applies to aseptically processed CSPs and CSPs stored refrigerated and at room temperature as well. For example, compounders have been making both progesterone and testosterone injectable medication in oil with years of data showing stability and safety stored at room temperature with BUDs of 180 days or more. The newly imposed restrictions from USP 797 regarding beyond use dating restricts a compounder to make a now inferior product. For example, if a compounder wanted to make testosterone in oil with a BUD dating of up to 180 days it would have to be labeled with frozen conditions. Testosterone’s solubility is directly correlated with temperature and at lower temperatures it crystalizes. Thus, the ideal storage temperature is controlled room temperature and frozen testosterone would be an inferior product. This restricts the compounder to put a shortened room temperature BUD per the newly implemented guidelines. This will again increase cost, decrease patient adherence and overall, negatively impact patients in Virginia without any scientific basis.
In summary I ask the Virgnia Board of Pharmacy to consider rejecting the new USP 797 beyond use dating and batch size restrictions in favor of the previous USP 797 requirements. Or at a minimum to put out guidance to the commonwealth that the board will exercise enforcement discretion while considering batch size and BUD dating. Compounders who have invested and created a contamination control strategy and stability program that includes environmental monitoring sampling to eliminate many of the concerns CEC may have should not be handicapped while trying to serve their patients in Virginia. I feel that it is important that the Virginia Board of Pharmacy be aware of all USP’s potential flaws and lack of scientific data to make an informed decision to overall benefit and protect the patients in the commonwealth. Ultimately adopting USP 797 in its entirety without careful consideration from the Virginia Board of Pharmacy on the practical and patient facing implications, introducing greater risk and cost into the sterile compounding process. I appreciate your attention on this important matter.