CSP Accuracy and Error Prevention Should Be Both a Leadership and Regulatory Mandate
Millions of compounded sterile preparations (CSPs) are produced each year, many in hospital pharmacies. The inherent risks in the sterile compounding process are numerous and include: 1) sterility and contamination concerns, which could lead to possible patient infections; 2) exposure of healthcare personnel, patients, and the environment to potentially hazardous drugs, which could result in adverse health effects; and 3) inaccuracies during preparation (e.g., wrong drug, wrong base solution, wrong diluent, wrong concentration), which could lead to harmful or fatal medication errors.
USP General Chapter <797> provides environmental and personnel standards to promote preparation of CSPs that are free from contaminants and are consistent in intended identity, strength, and potency. USP General Chapter <800> provides standards for safe handling of hazardous drugs to minimize the risk of exposure to healthcare personnel, patients, and the environment. Based on these standards, healthcare leaders are spending millions of dollars to update their facilities’ physical environments and pharmacy technology to be in compliance with the sterility standards in USP <797> and the hazardous drugs standards in USP <800>.
These USP standards represent much needed, high-leverage improvements that, when fully implemented, will improve the sterility of CSPs and reduce potential exposures to hazardous drugs. However, healthcare leaders have devoted fewer resources to ensure accuracy (e.g., right drug, right base solution, right diluent, right concentration) during the preparation of CSPs, risking potentially fatal medication errors. Many examples of harmful and fatal CSP preparation errors have been published in the ISMP Medication Safety Alert! during the last 25 years.
While some electronic health record (EHR) systems offer their own integrated intravenous (IV) workflow software modules, which utilize barcode scanning technology to verify product selection during the sterile compounding process, they typically lack imaging or gravimetrics to verify volumes of ingredients and completed CSPs. The most reliable way to ensure and achieve accuracy during the preparation of CSPs is through the consistent use of IV workflow management systems interfaced with EHR systems, which use barcode scanning technology to verify ingredients along with imaging and/or gravimetric tools to verify the volumes of ingredients and final preparations.
One health system’s experience
A large health system spent several million dollars on pharmacy construction and environmental improvements to achieve facility compliance with USP <797> and <800> standards. In conjunction with this work, the pharmacy director had requested a small fraction of what had been spent for USP <797> and <800> compliance to add an IV workflow management system to help improve and maintain CSP accuracy. Lacking a regulatory mandate for CSP accuracy, this request was not approved. In this health system, pharmacy technicians used the outdated “syringe pull-back” method for pharmacists to visually verify the amounts of CSP ingredients used after the preparations had been mixed. When the request for contracting with an IV workflow system was denied, the director independently managed to outfit each workbench/laminar flow hood with a computer tablet, barcode scanner, and camera, to supplement their EHR IV preparation software module. Within a few months, the combined technology was being used for all CSPs prepared in the pharmacy, including premixed IV compounds. The software and hardware combination was also used during the dispensing of certain high-alert medications (e.g., insulin vials) and vaccines, due to ongoing errors despite manual independent double checks.
The pharmacy director worked with information technology staff to receive weekly reports showing when the EHR pharmacy software with the supplemental hardware had detected a possible medication error during product selection when preparing CSPs, high-alert medications, and vaccines. The very first weekly report showed multiple instances of selecting and scanning wrong diluents, drugs, or strengths, particularly with antibiotics. One event caught the director’s eye, because it was clear that this particular drug selection error could have resulted in the death of an infant had it not been caught by the newly implemented IV software and hardware and corrected before leaving the pharmacy.
A physician prescribed IV fluconazole 12 mg/kg daily for a premature infant (1.5 kg) with invasive candidiasis in the neonatal intensive care unit (NICU). To prepare each dose, the pharmacy technician typically uses a premixed bag of fluconazole (200 mg in 100 mL of 0.9% sodium chloride) from which the required dose (18 mg [9 mL] in this example) is withdrawn into a syringe. In this case, the technician retrieved a 100 mL premixed bag from the fluconazole bin, but it was actually potassium chloride 40 mEq in 100 mL of fluid. Both the fluconazole and potassium chloride bags were packaged in 100 mL bags, and both bag labels presented the product name and strength in red font while other label text was black. It is presumed that the potassium chloride bag had been incorrectly returned to the fluconazole bin due to confirmation bias when glancing at the red font labeling and bag size (in many pharmacies these bags are typically stored apart from each other).
The potassium chloride bag was then taken into the cleanroom and placed on the workbench to prepare the fluconazole syringe. Fortunately, the bag was scanned before preparation of the syringe, and the error was caught prior to erroneously dispensing the potentially fatal dose of potassium chloride for the infant.
At pharmacy staff meetings, the director shared this error and other errors that were caught using the new technology rather than relying solely on manual independent double checks. Pharmacy staff agreed that events like these had been occurring and reaching patients regularly before utilizing the new software and hardware, and they were thankful that these errors were now being caught. Many pharmacy staff members also agreed that, even if the potassium chloride error had reached the infant and caused a fatality, the infant’s death would not have been traced back to the erroneously prepared CSP but instead associated with the infant’s medical condition or otherwise deemed an “unexplained death.”
Data submitted to the ISMP National Medication Errors Reporting Program (ISMP MERP) have repeatedly shown that the human-based, manual, post-production verification of CSP ingredients by pharmacy technicians and pharmacists is not reliable for detecting and correcting CSP preparation and dispensing errors. ISMP strongly believes that the barcode scanning of all base solutions, diluents, medications, and other ingredients is the minimum requirement for pharmacy CSP processes, and that overriding any compounding technology-based alerts requires the review of a pharmacist, not a technician acting alone.
Furthermore, ISMP recommends the acquisition and implementation of IV workflow management system technologies that incorporate barcoding to verify ingredients as well as imaging and/or gravimetrics to verify ingredient and finished CSP volumes. These technologies should undoubtedly be used when preparing chemotherapy and pediatric infusions. We urge healthcare leaders to support the acquisition and implementation of IV workflow management systems as soon as possible in organizations with CSP processes that lack these technologies. The next patient’s life could depend upon the decisions healthcare leaders make (or fail to make) today.
To this end, we are in sync with the THRIV Coalition, which argues that, just as critical technologies are required to meet sterility standards, IV workflow management systems should be required for achieving CSP accuracy. For guidance, go to the THRIV website to view a technology checklist of criteria that an IV workflow management system should meet or exceed. And while on the THRIV website, consider adding your name as a THRIV Champion for IV accuracy, acknowledging that fully efficient IV workflow management systems should be universally implemented and faithfully utilized by pharmacy compounding services to improve CSP accuracy.
In any facility that has yet to install the above technologies, all CSPs should be required to undergo an independent double check of the vials, ampules, prepared syringes, and container labels (drug and diluent) prior to adding them to the final solution, in place of the outdated “syringe pull-back” method or other manual post-production checking procedures.
Additional recommendations can be found in the ISMP Guidelines for Safe Preparation of Compounded Sterile Preparations. Also, one of the 2020-2021 ISMP Targeted Medication Safety Best Practices for Hospitals (#11) recommends eliminating the use of proxy methods of verification for CSPs (e.g., the “syringe pull-back” method, checking a label rather than the actual ingredients), and instead using technology to assist in the CSP verification process (e.g., barcode scanning verification of ingredients, gravimetric verification, robotics, IV workflow management systems).
ISMP plans to publish more detailed recommendations for pharmacy sterile compounding processes after analyzing the findings from our current ISMP Survey on Pharmacy Sterile Compounding. If you are a pharmacist or pharmacy technician who prepares or oversees the production of CSPs, please participate in our survey by September 18, 2020. We want to be sure that our future CSP recommendations thoughtfully address the challenges and safety concerns you have related to pharmacy sterile compounding, which we hope you will share with us via the survey.
Although the accuracy of parenteral sterile compounding processes is not as highly regulated as CSP sterility and the reduction of exposure to hazardous medications, it is a critically important component of medication safety and should not be overlooked. Healthcare leaders must direct the same level of resources to CSP error prevention as they do to engineering controls and construction to make the pharmacy and other clinical locations compliant with USP <797> and <800>. It is time for CSP accuracy and error prevention to be both a leadership and regulatory mandate. Similar to USP standards for sterility and hazardous drugs, perhaps standards and mandates would advance adherence and leadership prioritization of technologies that facilitate CSP accuracy and error prevention.