By Gina Shaw
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Craig Greszler, PharmD

A gravimetric workflow used to verify doses in the preparation of oral controlled substances provided accuracy and additional safety checks compared with the volumetric alternative, according to a recent study (Am J Health Syst Pharm 2023;80[16]:1063-1070).

The gravimetric workflow also offered users greater access to data, the authors, from BD (Becton, Dickinson and Co.) and Wesley Medical Center, in Wichita, Kan., reported. However, the practice also comes with logistical hurdles, including slightly longer preparation time.

“Anytime that you are adding safety checks, you are not necessarily going to see increased efficiency; it’s about putting the patient first,” said study author Craig Greszler, PharmD, the senior manager of medical affairs at BD.

Technology-assisted workflow (TAWF) combines software that can support and document the different steps of pharmaceutical preparation with various technologies such as cameras, barcode readers, robots and gravimetric systems with precision scales. The use of TAWF employing gravimetrics has become increasingly common in the IV compounding process, with various articles in the peer-reviewed literature documenting its benefits (Am J Health Syst Pharm 2018;75[17]:1286-1292; Am J Health Syst Pharm 2022;79[4]:230-238). But little has been published exploring the value of TAWF in oral medication preparation. “To my knowledge, this is the first time TAWF with gravimetric preparation has been studied in oral dosing,” Dr. Greszler said.

In a two-phase observational study, he and his colleagues first prepared solutions of oral controlled substances volumetrically; in the next phase, the same subset of medications was prepared gravimetrically via the same TAWF. Thirteen different medications were evaluated during phase 1 (1,495 preparations) and phase 2 (1,781 preparations).

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The investigators found that the deviation detection rate increased using gravimetrics (7.9% vs. 4.7%; P<0.01). The number of deviations detected nearly tripled (254 vs. 658) between phases 1 and 2. Doses prepared gravimetrically had a mean accuracy rate of 100.6% (mean achieved dose was 0.6% higher than the mean prescribed dose) and rejection rate of 0.99% (compared with the phase 1 rejection rate of 1.07%; P=0.67).

Compared with the volumetric workflow, the gravimetric workflow provided more specific information about the cause of the deviation, such as an incorrect initial bottle weight, an underdrawn or overdrawn syringe, an incorrect remainder weight, or volume withdrawn that was more than the container volume.

The gravimetric method presented some challenges: Despite a phase 2 goal of using gravimetric analysis for more than 80% of preparations, only 45.5% (811 preparations) were prepared using this workflow because adoption issues and dose size limitations prevented compliance. The mean compounding time also increased slightly but significantly in phase 2 compared with phase 1 (1:49 vs. 1:28 minutes; P<0.01).

Because of the extra steps needed to weigh the syringes and correct out-of-range doses, the overall average preparation time increased by 51 seconds per preparation. “But what you got in return was a threefold increase in potential error prevention,” Dr. Greszler said. These deviations would not necessarily always result in an error that could have affected patients, he added, “but if you consider that even half of those could potentially reach a patient, that’s still a pretty significant improvement.”

University Of Rochester Uses Gravimetrics for Safer Oral Therapy

One institution that has implemented gravimetrics in oral liquid repackaging is the University of Rochester Medical Center, in New York, which in 2022 began producing cups of oral medications using a unit-dose oral repackaging machine.

“With this machine, we use gravimetrics on a limited basis as a check process,” said David Webster, RPh, an assistant professor of public health sciences and the director of pharmacy operations. “We compiled a database of weights of the product and size we produce, and then use gravimetrics to weigh the batch as a check.”

Some batches contain several hundred doses, he added, “so we weigh each strip of cups as we go—usually five to 10 at a time depending on the size of the cup.”

Gravimetrics serves two primary purposes in this setting, he said. One is enhanced patient safety. “In a unit-dose cup, you can’t see the volume as easily as with an oral syringe, so there’s even more reason to do a check,” Dr. Webster said. Gravimetrics also helps mitigate drug diversion by “ensuring that we have repackaged the amount of drug we were intending to repackage, within a very small tolerance,” he continued. “We are committed that any controlled substance we repackage on this device will use the same gravimetric check.”

But there are some challenges with using gravimetrics in oral repackaging, and the benefit calculus is different than with IV sterile compounding. “Oral liquid batches are typically hundreds of doses for us, so the feasibility of weighing each dose upon producing is challenging,” Dr. Webster noted.

Furthermore, oral liquids have a different risk profile from that of sterile compounding. “Gravimetrics in sterile compounding makes a lot of sense for a lot of reasons, because you are often taking clear liquids and mixing them into other clear liquids, and you cannot see what was added,” Dr. Webster said. “Once that bag leaves the pharmacy, there is very little chance of someone picking up on an error.”

Errors may still occur when liquids are drawn up into oral syringes, but they can be mitigated by strategies such as barcode scanning, and “the opportunity to catch an error during visual checking after leaving the pharmacy is much higher, as you can see the dose that was measured,” Dr. Webster said. “Additionally, with oral liquids, you are typically dealing with a less risky therapeutic impact compared with an IV preparation. An error is still critical to avoid, but the potential for significant poor outcomes has driven the focus on sterile compounding.”

Whether the cost and time involved with implementing gravimetrics for oral repackaging are valuable remains an open question, Dr. Webster said. “We’ve grappled with what is the real payoff in safety versus the logistics,” he acknowledged. “If you are batch-producing a lot of repackaging jobs like we do, [with] 300 to 500 syringes in a batch, the idea of introducing gravimetrics for each individual syringe has some feasibility challenges. That’s not to say that we wouldn’t do it if it added significant safety benefits, but there is definitely an impact on workflow.”

—G.S.

A Manageable Learning Curve

There will be a slight increase in the time it takes to prepare an oral dose using gravimetrics, agreed Rita Jew, PharmD, the president of the Institute for Safe Medication Practices. “But based on the experience of implementing IV workflow software using TAWF and gravimetrics for injectable medications, after the initial learning curve, that time will decrease significantly as people get more comfortable with the workflow,” she said. “I would be interested to see a follow-up study from these authors in the same setting six months later; there might not be a statistically significant difference in mean compounding time.”

Despite the benefits, widespread adoption of TAWF in the oral preparation setting faces barriers. “There is not any one organization or group pushing for orals to undergo the same type of scrutiny that IV preparations are,” Dr. Greszler said. “Perhaps the reason is that we don’t have any known blockbuster cases involving errors in this area. Are they occurring? Possibly; we don’t know, but behind the scenes we could be over- or underdosing a lot of different patients.”

Now that the November 2023 deadline for compliance with USP General Chapter <795> on nonsterile compounding has passed, Dr. Greszler speculated that this might convince some health systems of the value of using gravimetric TAWF to prepare oral medications. “This chapter includes new revisions on what is required for documentation, and even outside of its safety benefits, TAWF is also useful because it can help with those documentation issues,” he said.

The sources reported no relevant financial disclosures.

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