Earlier this year, the United States Pharmacopeia (USP) took the first in a series of steps to revise the standards for compounding nonsterile and sterile preparations, and aligning the relevant chapters with USP <800> (“Hazardous Drugs — Handling in Healthcare Settings”), which was published in 2016 and goes into effect December 1, 2019.

The public comment period for USP <795> closed in late July of this year, at the same time that USP introduced their Proposed Revision for GC <797>, with a public comment period that will close on November 30, 2018.

USP <797> specifically addresses “Pharmaceutical Compounding — Sterile Preparations.” Like USP <795>, the Proposed Revision introduces substantive changes that affect a range of categories, particularly for institutional pharmacies.

Understandably, these revisions could have a sizable impact on facility workflow and finances, so it’s incumbent on pharmacists and executives to review USP <797> and determine how the scope of the proposed changes could actually influence their practices. 

Here are some of the revisions likely to have the most significant consequences.

Shifting definitions for sterile compounding

As is case for the revisions to nonsterile compounding rules, this chapter also brings fundamental change to the medication compounding model.

The previous version of <797> outlines three categories of compounded sterile products: low-risk, medium-risk, and high-risk. The Proposed Revision to GC <797> consolidates those into two: Category 1 and Category 2.

This shift is likely to have the greatest impact on facilities that were formerly classified as medium-risk compounders, which describes the vast majority of hospitals in the U.S. Many of these facilities will now be graduating to a higher level of compounding “risk” in Category 2 and, as such, will have a higher bar to clear to remain in compliance.

USP <797> also introduces a new definition of “what constitutes compounding.” In the case of a “bag and vial” system (in which a medication vial is attached, with adaptor, to the bag that it needs to be mixed in, for infusion), if a nurse is on the nursing unit and attaches the bag and vial, that is not regarded as compounding.

However, if a batch of these is being attached within the pharmacy to be put into different automated dispensing cabinets, that process is now considered “sterile compounding” and would need to be done inside an ISO Class 5 hood.

Investment of time

Previously, mandatory checks such as glove fingertip testing and media fill testing have been done annually, but <797> will now mandate that these be performed semi-annually.

The person responsible for this QA will now effectively have their workload doubled: in the example of a mid-sized facility — with 25 employees — the process (including training, visual observations, and the testing mechanics) could be estimated to take two hours per employee. That represents an additional 50 hours of work, not to mention a doubling in the cost of supplies.

Similarly, the requirement for surface sampling (literally wiping surfaces in various compounding areas to test for bacterial contamination) is mandated to be done monthly in the new version of <797>; the previous version required that this testing need only be done “periodically,” with that term defined loosely. For most facilities, then, this redefinition will result in additional time requirements.

Facility renovations: Another major adjustment for facilities that will be newly deemed to be “Category 2 compounders” will come in the form of new requirements for what qualifies as a “classified area” for sterile compounding.

Many hospitals, currently categorized as medium-risk facilities, perform compounding using a compounding aseptic containment isolator (CACI). Under the current rules, facilities are able to place these units in unclassified areas and assign usual beyond-use dating (extending as far as 45 days) to the compounded products made there.

But, per the new version of <797>, if you have a CACI in an unclassified area, anything compounded there can only have a maximum 12-hour beyond-use date at controlled room temperature.

In the case of a pharmacy that wants to be able to mix medications and provide greater than a 12-hour beyond-use date at controlled room temperature, that team will now be required to create an area that would bring them up to Category 2 standards.

If they have simply had an isolator in their facility where they’ve been mixing, they will now have to create a classified compounding area that’s in compliance. Specifically, this facility might now be required to construct its first compounding suite, comprised of a negative pressure buffer room (for hazardous medications), positive pressure buffer room (for sterile compounding), and an ante room.

Based on some estimates, the cost to construct a brand new compounding suite could reach the neighborhood of one million dollars.

Multiple-dose preparations: A rule that is completely new to this General Chapter introduces rather stringent guidance related to beyond-use dates for multiple-dose compounded sterile preparations.

If, for example, a pharmacist makes a stock solution of Pepcid in a 60 mL IV bag, and subsequently draws out 1 mL of that drug to make an individual patient dose, the stock solution in that larger bag becomes a multiple-dose compounded sterile product. Per the Proposed Revision to <797>, unless antimicrobial effectiveness testing is performed, the stock solution can only have a beyond-use date of six hours.

Given that an extreme minority of hospitals perform their own antimicrobial testing, this will either place a significant burden on them to start adding this time-intensive function to their workload, or it creates a scenario that will result in excessive waste.

Particularly in the case of children’s hospitals, which frequently work with medications that need to be diluted in order to get the proper dosing for the pediatric population, they could be faced with surplus containers of sterile products that can now only be kept for six hours — less than the time of one shift, in most cases.

Next steps

Given the breadth of likely new requirements, it is incumbent on facility managers to assess their operations to determine what compliance issues might arise if USP <797> is implemented as currently written.

Important to note, though, that they have an opportunity, before November 30, to write to USP to request clarification or make a well-reasoned case for revisions to the chapter before it is formalized.

In any case, this latest regulatory activity needs to be on the radar — now — of any facilities that compound sterile medication for patients.

Kenneth Maxik, MBA, MBB, FACHE, is director of patient safety and compliance for CompleteRx. He has more than 20 years of pharmacy operations and management experience and works closely with health organizations across the country to help them stay ahead of current and imminent regulatory standards. www.completerx.com