Compounding
Rachel Balick
Proposed revisions to USP General Chapters <795> and <797>, which establish standards for nonsterile and sterile compounding, respectively, raised the ire of compounding pharmacists because of their stringent rules around beyond-use dates (BUDs). In response, the USP Compounding Expert Committee considered appeals by pharmacists and the professional associations that represent them and issued decisions; however, stakeholders who submitted appeals requested further review by a panel with members appointed by USP. In accordance with USP bylaws governing its formal appeals process, the organization postponed official dates of the revised chapters until further notice. Publication of a new chapter on radiopharmaceutical compounding, <825>, was also postponed.
In the meantime
In the interim, the current content of <795>, last revised in 2014, and <797>, last revised in 2008, will remain official—including the section on radiopharmaceuticals as compounded sterile preparations (CSPs), said Jeanne Sun, PharmD, scientific liaison and manager at USP.
“USP is working with individual appellants to schedule hearings on the appeals. USP intends to treat the hearings as open meetings unless appellants request otherwise—for example, to protect confidential information,” Sun said. After deliberation, the Appeals Panel will either deny the appeals, resulting in the Expert Committee’s approved standard becoming official; or grant one or more of the appeals, resulting in a remand of the standards to the responsible Expert Committee for further evaluation, stakeholder engagement, revisions, or a combination of these.
From a compendial perspective, Sun added, early adoption of the revised standards in advance of the official date by states, regulators, accreditation bodies, and pharmacists is allowed unless specified by USP General Notices 3.10 (at the time of publication). “States, regulators, and accreditation bodies may make their own determination on implementation and enforcement of the current official standards or postponed revised USP compounding standards,” she said. “Stakeholders should speak with the appropriate regulators in their state to determine what may be required.”
The objections
Compounders say strict, arbitrary, and short BUDs could have a devastating impact on patient access, particularly patients who require sterile CSPs. Making smaller, more frequent batches increases the risk of contamination or other quality errors. Pharmacies could even find it so burdensome to comply with new restrictions that they’ll leave the compounding space altogether, said Michael Blaire, BSPharm, vice president of government and regulatory affairs at Wedgewood Pharmacy in Scottsdale, AZ, former chair of the APhA Special Interest Group on Compounding, and president-elect of the Alliance for Pharmacy Compounding (formerly the International Academy of Compounding Pharmacists).
Blaire worries that restrictions for CSPs will limit compounders to a product with 48 to 96 BUDs if they don’t do sterility testing. “Getting the results of testing that will allow a 30-day BUD takes anywhere from 14 to 20 days. So, effectively if you do the testing, you’re dispensing a product that has maybe a 10-day BUD on it.”
Patients would feel the effects. “Let’s say you have a child with autism, and you’ve been getting a bottle of methylcobalamin for injections every 30 days or 45 days,” Blaire said. “Now you would have to get three bottles a month because the stuff that you’re getting is only going to have 10 days’ useful life on it. So, your cost has tripled.” The higher costs and more frequent refills could lead to noncompliance and poorer patient outcomes, particularly around <797>.
“And because it doesn’t pay to make large batches of product that you’re not necessarily going to be able to sell, the pharmacies are going to have to make smaller batches more frequently, which statistically increases the chances of having an accident,” he added.
USP disagrees. “Based on the revised chapter, for aseptically prepared CSPs that have undergone sterility testing, BUDs of 30 days at controlled room temperature, 45 days refrigerated, or 45 days frozen can be assigned,” Sun said.
Sun said the revisions to the BUDs were updated using a risk-based approach since it is difficult to predict the stability and microbial susceptibility for all the different types of nonsterile and sterile preparations. “These revisions were necessary to ensure that patients receive medicines that are the right strength, quality, and free of contaminants.”
What’s next?
Sun said USP cannot predict or project a future official date for any of the chapters while the appeals process remains active. “Regardless of the outcome of the appeals process, USP would not reestablish an official date for <795>, <797>, or <825> without granting another 6-month implementation period, at a minimum,” she said. Any decisions on the appeals … will not foreclose the possibility of future revisions.
“USP is committed to providing support to advance the public health goals of quality compounding, while preserving patient access to medications,” Sun added. “USP will continue ongoing engagement and collaboration with stakeholders and offer tools and resources.”