Pharmacy Practice News - Special Edition December 2021

The 2021 Annual Compendium of Educational Reviews

Lean Thinking for CSTDs 10 Tips for Adding Quality to Your 503As and 503Bs A survival guide for audits and inspections Practical Considerations for

Implementation of Biosimilars in Oncology IV-WMS: Slow Adoption Continues to Threaten Compounding Safety January Through December 2020

Medication Errors: The Year in Review Parenteral Nutrition Safety

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Pharmacy Practice News

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EDITORIAL BOARD

NUTRITION

ADMINISTRATION

Beverly Holcombe, PharmD, BCNSP, FASHP, FASPEN Chapel Hill, NC

ART/PRODUCTION STAFF Michele McMahon Velle, MAX Graphics/Creative Director

Robert Adamson, PharmD, Livingston, NJ

Vanessa Kumpf, PharmD, BCNSP, Nashville, TN

James A. Jorgenson, MS, RPh, St. Paul, MN

ONCOLOGY

Indu Lew, PharmD, Livingston, NJ

Cindy O’Bryant, PharmD, Aurora, CO

AMBULATORY CARE

Lisa Holle, PharmD, Farmington, CT

James O’Neill, Senior Systems Manager

Ali McBride, PharmD, MS, BCPS, Phoenix, AZ

Marty Barbieri, Associate Director of Production

Meghan D. Swarthout, PharmD, MBA, BCPS, Sallston, MD

Frank Tagarello, Senior Art Director/Managing Director MAX Graphics

Sara S. Kim, PharmD, BCOP, New York, NY

ANESTHESIOLOGY/PAIN

ORGAN TRANSPLANT PHARMACY

Julie A. Golembiewski, PharmD, Chicago, IL

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PEDIATRICS

McMAHON PUBLISHING

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CARDIOLOGY

PHARMACOGENOMICS

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CNS/PSYCHIATRY

REIMBURSEMENT

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STERILE COMPOUNDING

CRITICAL CARE

Kristina N. Bryowsky, PharmD, MBA, BCPS, Fenton, MO

Judi Jacobi, PharmD, FCCM, Indianapolis, IN

TECHNOLOGY Thomas Van Hassel, RPh, Yuma, AZ

INFECTIOUS DISEASES Steven J. Martin, PharmD, BCPS, FCCM, Toledo, OH David P. Nicolau, PharmD, Hartford, CT Jason Pogue, PharmD, Detroit, MI LEADERSHIP Ernest R. Anderson Jr., MS, RPh, Boston, MA

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TABLE OF

CONTENTS

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Lean Thinking for CSTDs Fred Massoomi, PharmD, RPh, BCSCP, FASHP Seth Eisenberg, RN, OCN, BMTCN Jim Jorgenson, RPh, MS, FASHP

10 Tips for Adding Quality To Your 503As and 503Bs A survival guide for audits and inspections Gina Shaw

Practical Considerations for

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Implementation of Biosimilars In Oncology Douglas Hackenyos, PharmD, BCOP

Parenteral Nutrition Safety Jay M. Mirtallo, MS, RPh, BCNSP, FASHP, FASPEN Phil Ayers, PharmD, BCNSP, FMSHP, FASHP

January Through December 2020

31 43 4

MCMAHON PUBLISHING GROUP

Medication Errors: The Year in Review Institute for Safe Medication Practices

IV-WMS: Slow Adoption Continues To Threaten Compounding Safety Adam Leitenberger

Cost Saving Time Saving Waste Saving Life Saving

ADVANCED

TM

To learn more visit:

Universal, Needle-Free 20mm Admixture Device for Immediate Use IV Administration West and the diamond logo and By your side for a healthier world, are trademarks or registered trademarks of West Pharmaceutical Services, Inc., in the United States and other jurisdictions.

Vial2Bag AdvancedTM and Blue Vial Adapter are trademarks and registered trademarks of West Pharma. Services IL, Ltd., a subsidiary of West Pharmaceutical Services, Inc. Copyright © 2021 West Pharmaceutical Services, Inc. #11438 • 0821

If you employ the use of CSTDs in your facility to protect healthcare workers, you need to read these studies: Vapor Containment Efficacy of Air-Cleaning CSTDs with 3 NIOSH Surrogates Vishnuprabha (Dhanapal) Vogel, PharmD, BCPS, BCOP, Szlaczky, Mark, BSc, Pharm D, Rida, Nada, Pharm D, Mazur, Izabela, Pharm D, Henry Ford Hospital, Detroit, MI

https://bit.ly/2YfTJZn

An Assessment of Exposed Syringe Inner Walls as a Route of Exposure from Hazardous Drugs Stephen F. Eckel, PharmD, MHA, University of North Carolina Eshelman School of Pharmacy

https://bit.ly/3l6apLd

Evaluation of Vapor Containment Efficacies of Air-Cleaning CSTDs and Regular Syringes Using NIOSH Hazardous Drug Surrogates Phillip Schwieterman, PharmD, Kathryn Plahn, BA, CPhT, CSPT, University of Kentucky, Lexington, KY

https://bit.ly/3kFHIob

Monitoring Contamination on Inner Walls of Syringes Used for Preparation and Administration of Hazardous Drugs University Hospital Leuven Belgium, Exposure Control Sweden AB

https://bit.ly/3i8Rn5j

Efficiency of Closed System Transfer Devices (CSTDs). Comparative study Dr. Elena Khanonkin, Dr. Tikhon Filippov, Dr. Valery Bulatov and Prof. Israel Schechter, Faculty of Chemistry, Technion – Israel Institute of Technology Haifa 32000, Israel | israel@technion.ac.il

https://bit.ly/3zN6dnH

Given all the evidence contained in these studies, shouldn’t health systems reconsider how CSTD purchase decisions are made?

*Studies sponsored by Equashield **NIOSH did not play any role in conducting these studies

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Lean Thinking for CSTDs FRED MASSOOMI, PHARMD, RPH, BCSCP, FASHP SETH EISENBERG, RN, OCN, BMTCN Source: Rx3 Compounding Pharmacy

JIM JORGENSON, RPH, MS, FASHP St. Paul, Minnesota Visante Inc

L

ean management principles have been used effectively in manufacturing scenarios for decades, particularly in Japan.

More recently, the use of Lean concepts in health care1 has

caught the interest of regulators, who suggest that the discipline be a guide for training pharmacists who are involved in pharmacy compounding procedures. One of those procedures—the use of closed system drug-transfer devices (CSTDs)—may well be an under-recognized area for Lean applications.

The first step is to understand the basics of Lean management principles. Lean thinking begins by driving out waste so that all work adds value and serves customers’ needs. Identifying value-added and non–value-added steps in every process is the beginning of the Lean initiative. More specifically, Lean thinking comprises 5 principles: 1) defining value, 2) mapping the value stream, 3) creating flow, 4) using a pull system, and 5) pursuing perfection.2 Too often in our everyday work in health care, we don’t really think about these principles as we make decisions about technology or design work processes.

Often, consideration for things such as value stream mapping only happens once something has broken

and needs repair. But the application of Lean principles should be a consideration on the “front end” of technology selection and process design and should periodically be reevaluated for all key processes.

By dismissing Lean principles, health systems lose the opportunity to benefit from its tool kit of efficiencies, consistency, safety, and waste reduction. Also lost is the opportunity to improve complex processes while delivering substantial gains to the bottom line.3 Given those benefits, it’s not surprising that the use of Lean concepts in health care has caught the interest of the Massachusetts Board of Registration in Pharmacy, which has published “An Introduction and Guide to the Practices and Implementation of Lean

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Table. Closed System Drug-Transfer Devices Device

Manufacturer

FDA Cleared

BD PhaSeal

Becton Dickinson and Company

1998

Spiros

ICU Medical Inc

2005

ChemFort or OnGuard with Tevadaptor

Simolivia Healthcare Ltd B. Braun (US distributor) Teva Medical Ltd (manufacturer)

2006

ChemoClave

ICU Medical Inc

2006

Equashield

Equashield LLC

2008

ChemoLock

ICU Medical Inc

2013

EquaShield II

Equashield LLC

2014

Halo

Fresenius Kabi (US distributor) Corvida Medical Inc (manufacturer)

2015

Arisure

Baxter International Inc

2017

BD PhaSeal Optima

Becton Dickinson and Company

2018

NeoShield

JMS North America

2018

ProSeal

Epic Medical Pte Ltd

2020

Source: Visante.

Concepts in a Pharmacy Setting.” The document notes that “sterile compounding, complex non-sterile compounding, and institutional sterile compounding pharmacies shall ensure their employees are trained in lean concepts before renewing their pharmacy license.”4

Making the Initial Assessment Since the introduction of the first CSTD to the US market in 1998, many new CSTDs have emerged, providing organizations with a variety of options that best fit their compounding and drug administration processes (Table). Preferred features of a CSTD, based on general Lean principles, would include intuitive connections, pre-bonded components to limit the number of attachment/disconnection steps, pre-purging displacement air into the system, wetting potential of filters, and locking mechanisms that clearly indicate complete connection. In addition, systems also should limit the pressure required to engage and disengage the components, thus reducing the risk for repetitive stress injuries. The risk for repetitive motion injuries is a concerning yet underappreciated issue with drug compounding.5 Each device is very unique in the number of components, component options, mechanism of protection, integration with existing systems and costs, and, thus, should be assessed individually as a system versus generically categorizing the devices as a “CSTD.”

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The overall effect of integrating any device into medication safety systems must consider each end user’s use of the device(s), standard operating procedures, primary engineering controls, infusion pumps, disposal, staff perception of safety, number of components, and overall costs.

Another factor to consider is the FDA’s clearance code for CSTDs, “ONB.” The code is applied to devices that have indications for use with antineoplastic and other hazardous drugs. Regardless of their technology, all devices cleared by the FDA under the ONB code are considered CSTDs.

Lean Attributes of CSTDs Within updated USP Chapter <800> standards6 and nursing and pharmacy guidelines, the introduction of CSTDs was mandated for antineoplastic drug administration and recommended for compounding of hazardous drugs. In deciding which CSTD to deploy and how to effectively integrate a CSTD into compounding and administration processes, it is useful to think about these processes in the context of the 5 Lean principles.

1. DEFINING VALUE Value at the simplest level is the quality delivered plus the customer satisfaction at a defined cost. It is imperative for a new technology such as a CSTD to meet the actual needs of the users. To select the

Figure. Almost all CSTD manufacturers make options that allow connecting integrated CSTD tubing with the IV bag.

When direct spikes (shown above) are used in compounding, they eliminate the need to prime tubing in the BSC. BSC, biological safety cabinet; CSTD, closed system drug-transfer device

optimal product and integrate that most effectively and efficiently into pharmacy and nursing practices, end users have to clearly understand what they want and the price they can afford. For a CSTD, this can be challenging because the technology has two main user groups in nursing and pharmacy, both of which come with different needs and elements driving satisfaction. The primary value proposition for both health care professionals in regard to choosing a CSTD is protection—for their patients and for themselves. Compounding and administering medications require diligence in balancing timeliness and expected attributes while ensuring safety from needlesticks and exposure to hazardous drugs.

2. MAPPING

THE

VALUE STREAM

In value stream or process mapping, the goal is to use the customer’s defined value as the desired end point and then to identify and map all the activities in the processes that contribute to these values. Activities that do not add value to the end user would be identified as waste. The waste can be further delineated into two categories: non-value added but necessary and non-value added and unnecessary. The first category should be reduced as much as possible, and the second category is just pure waste and should be eliminated to the maximum extent possible.

By reducing and eliminating unnecessary processes

or steps in compounding and administration, including the steps for CSTD application, users can improve the likelihood that they are getting exactly what they want while reducing their costs. In compounding, eliminating the concern for possible needlesticks, overpressurized drug vials resulting in spills/sprays, and lapses in aseptic technique due to individual variations with the use of traditional compounding tools (ie, syringe in combination with a needle) are non-valued waste that may be eliminated by a CSTD.

3. CREATING FLOW After reducing wastes from the value stream, the next consideration is to ensure that the flow of the remaining implementation steps runs smoothly, without interruptions or delays. From the moment a CSTD is integrated from the vial, it is in a system of “flow” from compounding, to delivery, to administration and, finally, to disposal. Health systems that employ CSTDs minimize angst by not having to worry about needlesticks, drug vaporous sprays, lapses in aseptic technique, and Luer line disconnections and spills, which can lead to delays in therapy and loss of revenue.

Further aiding flow, almost all CSTD manufacturers make options that allow connecting integrated CSTD tubing with the IV bag. When these direct spikes are used in compounding, they eliminate the need to prime tubing in the biological safety cabinet. This not only

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frees up pharmacy or technician time but also removes large, bulky items from the sterile compounding area.

Examples of direct spikes can be seen in the Figure.

4. ESTABLISHING PULL Inventory is considered one of the biggest wastes in any production system. The goal of a pull-based system is to limit inventory and work-in-process items while ensuring that the requisite materials and information are available for a smooth workflow. The uniqueness of each CSTD brings a significant variation in the number of components required for use.

It is important to understand each component of CSTD systems to determine which components are required for a site’s medication management processes. Value stream mapping is a valuable tool to visualize the number of steps requiring CSTD components and which components are required. If you do not have all required components, this will result in delays, frustrations and safety issues. The importance of nursing and pharmacy defining the specific CSTD components and putting them together helps to understand what works for a particular site.

5. PURSUING PERFECTION Waste is prevented or minimized through the achievement of the first 4 Lean steps. The fifth step of pursuing perfection makes Lean thinking a continuous process improvement endeavor. Pharmacy and nursing should actively promote and encourage continuous learning. As such, they always should look to find ways to use CSTDs to make the process of hazardous drug compounding and administration safer, more efficient and more cost-effective.

Future application of CSTDs includes use outside of hazardous drugs handling, where the noted Lean advantages can be applied to all sterile compounding, and the application of the devices to minimize potential medication waste through drug vial optimization programs.7 As the individual devices continue to evolve and the demand for sterile compounding continues to increase, CSTDs can serve as tools for growth.

Standard Work Another hallmark of Lean management is eliminating variations in practice that can lead to increased waste and decreased quality and safety. CSTD components are designed to be modular and integrated in such a way as to standardize a specified method of

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drug compounding and drug administration. In addition, a well-designed CSTD provides a safe method for flushing tubing after the drug has been administered. 8 Since nurses do not have the benefit of working in the same type of contained, controlled environment associated with compounding, the proper use of CSTDs helps to prevent widespread environmental contamination in the patient care areas. In addition, the more intuitive a system is to use, the easier it is to lessen variances in compounding and to facilitate effective training.

The device that integrates into pharmacy and nursing practices with perceived protection from both disciplines is the ideal CSTD. Other Lean attributes to consider are devices with the least number of components, packaging, steps for user-to-device interfacing, steps for device-to-device interfacing and drug transfer. These attributes should be fully vetted and validated at each site to ensure the advertised benefits of a specific CSTD meet the expectations of the staff using the devices. Ultimately, a CSTD should meet the efficiency needs of pharmacy and nursing with the benefits of saving time, controlling costs, minimizing line items, and training.

References 1.

Going Lean in Health Care. IHI Innovation Series white paper.

Institute for Healthcare Improvement; 2005.

2.

Womack JP, Jones DT, Roos D. The Machine That Changed the World. Free Press; 2007.

3. Shaw G. The ‘Gemba walk’ and its role in compounding quality assurance. Pharmacy Practice News. June 25, 2020. Accessed November 1, 2021. bit.ly/3tsYxV0 4. The Commonwealth of Massachusetts; Executive Office of Health and Human Services; Department of Public Health; Bureau of Health Professional Licensure; Massachusetts Board of Registration in Pharmacy; Policy No. 2016-013: An Introduction and Guide to the Practices and Implementation of Lean Concepts in a Pharmacy Setting. August 2016.

5. Abbot L, Johnson T. Minimizing pain resulting from the repetitive nature of aseptic dispensing. Hosp Pharm. 2002;9:77-79.

6. USP General Chapter <800> Hazardous Drugs— Handling in Healthcare Settings. Accessed November 1, 2021. www.usp.org/compounding/ general-chapter-hazardous-drugs-handling-healthcare 7.

Buckley B, Buckley J. Is drug vial optimization set to expire?

Pharmacy Practice News. June 8, 2018. Accessed November 1, 2021. bit.ly/3qUg9aI

8.

Polovich M, Olsen M. ONS Safe Handling of Hazardous Drugs. 3rd ed.

Oncology Nursing Society; 2018.

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10 Tips for Adding Quality To Your 503As and 503Bs A survival guide for audits and inspections “What is tested is not sold; what is sold is not tested.”

That’s an observation from Ian F. Deveau, PhD, the division director of the FDA’s Center for Drug Evaluation and Research Office of Manufacturing Quality. And it’s why pharmacies that do sterile compounding cannot rely solely or even primarily on testing of their compounded sterile preparations to ensure sterility and potency, said Amy Summers, PharmD, a consultant to the compounding industry, during a session at the 2021 Compounding Pharmacies Grand Salon, held virtually.

If, for example, you make 100 units of a compounded sterile preparation, you don’t test them all for endotoxins, sterility and subvisible particulates; instead, you test a small percentage of the batch. Those that come back having passed will not be delivered to a patient, unlike the remaining untested units. “You can’t rely on testing to say that you produce quality preparations,” Dr. Summers said.

She noted that, in 2020, the FDA began teaching boards of pharmacy how to apply Current Good Manufacturing Practice standards to the compounding pharmacy setting and predicted an impending paradigm shift. “The regulators will be expecting you to scientifically justify everything you do,” Dr. Summers explained.

“Saying you follow the standards just won’t be good enough. We’re going to need to have quality built into, not tested into, our systems, from the facility and equipment to materials and personnel. Quality has to be at the center of everything that you do.”

Scientific approaches to ensuring sterility or potency include process validations, media fills, best practices in gowning and cleanroom behavior, appropriate environmental and personnel monitoring, and appropriate cleaning and disinfection programs. “If you have all that working for you, you know you are making a

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good-quality product,” Dr. Summers said.

She broke down quality management systems for sterile compounding pharmacies into 10 key categories: Organization and personnel. “Who’s responsible and who does what? A clear organizational chart provides a visual overview that helps everyone understand, from a legal standpoint, which personnel are allowed or not allowed to perform certain functions,” she said. “Make sure you have one and keep it current. For personnel, you need clear training and competency requirements in aseptic operations, documents, visual inspection, labeling and packaging, cleaning and disinfection, and SOPs [standard operating procedures] like gowning and handwashing. Lots of folks just have their employees read the SOPs, provide one demonstration and then jump into qualification without providing proper mentorship and training. You must document that training and how it was performed.”

Building and facilities. “Your primary and secondary engineering controls, such as ISO [International Organization for Standardization Class] 5 and ISO 7 environments, must work as intended. Air movement patterns, air exchange, particle counts, pressure differentials, temperature and so on must meet defined industry standards,” Dr. Summers said. If you have an aging facility, she recommended certifying spaces semiannually. “Don’t just take the certifier’s word for it. Study your reports, watch the unidirectional air flow patterns in dynamic smoke studies to ensure there are no weak points anywhere near the critical site or aseptic working area. And don’t stress your cleanrooms beyond their studied maximum capacity. If there are two people allowed at a time in fill suite A, then you’d better not have three in there.”

Equipment. SOPs should exist for the calibration, qualification, maintenance and documentation of all equipment. “Don’t say, ‘Use pH meter per manufacturer instruction,’” Dr. Summers said. “Go into detail about how to use it at your organization. What is the relative humidity of the room while the meter is in use? Will you use one particular pH meter for preparations having highly acidic values and another for highly basic, or will you use the same one? Your SOPs need to be highly specific.”

Critical supplies. A lack of qualifying materials has led to several recalls in compounding pharmacies and compromises in patient safety, Dr. Summers noted.

“It’s not enough to buy from a supplier that ‘everyone uses.’ Each must be qualified, with the latest regulatory audit report, and if you’re a 503B, complete testing of the first three lots of materials and complete testing of one lot per year.”

503As that use active pharmaceutical ingredients (APIs) to compound sterile preparations from non-sterile materials “should consider testing critical parameters of APIs (e.g., assay, endotoxins, bioburden) to confirm they

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meet specification and, therefore, quality,” Dr. Summers stressed. She also advised pharmacies to create a survey outlining what you want to know from each supplier, and if you can’t travel to them, perform a “desk audit” by asking for SOPs or validation documents of interest to you.

Production and process controls. Stability and beyond-use dating (BUD) assignments for all preparations are essential elements of process and production controls in compounding. “How should this preparation be stored once it’s finished; how long is it good for? Do pertinent staff know how to assign BUD and store each product?” Dr. Summers asked. “Is that information easy to find on the master formula and compounding record for each compound?”

She added that pharmacies relying on USP or manufacturer directions for BUD assignment should still perform period spot testing regularly. For both 503As and 503Bs, Dr. Summers recommended that those tasked with overseeing compounding quality make it a daily habit to walk the floor and audit the process firsthand.

“This doesn’t have to be lengthy if you do it daily,” she said. “Even 10 minutes will help you gauge the quality built-in status of your organization.”

Labeling and packaging controls. “Whether you’re a major 503B or a small compounding pharmacy, proper labeling procedures include security, selection, printing, application and reconciliation,” Dr. Summers said. Security: Where are your labels stored, and who can access them? Selection: Are they all blank, white and similar in appearance, or at least partially preprinted? How do you prevent mix-ups? Printing and application: Who prints and applies them, and when is this done? Reconciliation: If you’re batch labeling, is each label accounted for at the end of preparation? Does the preparation count match the label count? What happens to any leftover labels?

Holding and distribution/dispensing. 503B outsourcers have no choice but to hold batches in quarantine until batch release results are back, but for 503As, there’s no quarantine period for single-unit preparations associated with a prescription. “Nonetheless, there is a short period where the compound is on hold waiting for pharmacist approval, and there need to be controls in place preventing compounds from going to the floor or being dispensed prior to that approval,” Dr. Summers said.

Laboratory controls. “If you use a third-party lab for stability studies or production batch release, qualify them like you did your suppliers,” Dr. Summers recommended.

Documentation. Your pharmacy should have documentation control and security for handling the generation or updating of SOPs, master formulas, protocols, compounding records and other such

documents. “A good records management system assigns numbers to each control document, tracks revisions over time and maintains retrievable copies for review in a second location or electronically,” Dr. Summers said.

Returned and salvaged drug products.

“Make sure to define a rework procedure if you intend to allow one for salvaging drug preparations,” she concluded. “This is used typically when a batch or compound fails the acceptance criteria and needs to be reprocessed before release or dispensing. Examples include pH readjustment, filtering, relabeling and repackaging. It’s also advised from a regulatory compliance perspective to have a written policy describing that returned drugs that have previously left the pharmacy are not allowed to be dispensed to a different patient.”

Aim for ‘Quality Built In’

‘Don’t stress your cleanrooms beyond their studied maximum capacity. If there are two people allowed at a time in fill suite A, then you’d better not have three in there.’

If you have a philosophy of “quality built in” at your compounding pharmacy, you will probably perform well on any inspec—Amy tion by the FDA or state board of pharmacy.

But it can be helpful to build your facility’s “inspection readiness,” said Helen McKnight, PharmD, MBA, BCSCP, the director of pharmacy at Princeton Baptist Medical Center, in Birmingham, Ala., in another Grand Salon session.

“You should be ready to be inspected at any time, with a regulatory preparation team,” said Dr. McKnight, who is the first pharmacist in Alabama to earn the board-certified Sterile Compounding Pharmacist designation. That team should include your facility’s compliance officer, clinical staff members who work directly with patients, a representative from human resources, your engineering manager, a construction director if your facility has one and legal counsel if your compliance officer is not an attorney. Dr. McKnight recommended that the team meet at least once a month, especially if there is a scheduled regulatory inspection coming up soon.

“In 2019 and 2020, inspection trends really focused on hand hygiene, forced air mixing, and documentation and follow-up,” Dr. McKnight said. “A lot of inspectors have been asking compounding pharmacies to pull their certification records and documentation of staff training. They have been particularly interested in ensuring that the person who is most responsible for [USP Chapter] <797> has an understanding of the records they’re looking at, particularly from certification companies.”

Dr. McKnight suggested establishing an inspection protocol so that staff know exactly what to do if an inspector shows up at your pharmacy. “Ask for their credentials, and have an assigned person to accompany the inspector throughout the facility,” she said. “It’s helpful to

Summers, PharmD

have a designated area where the inspector can review documents and meet with staff. Coach your personnel to respond truthfully only to the questions they are asked, and not to volunteer any additional information.”

Regulatory preparation teams also should be prepared to outline an appropriate response to any citation that might be received, which could range from a warning notice, a written correction order, a citation, to even criminal charges. “That’s rare, but it could happen, and has happened,” Dr. McKnight said. “An appropriate response to a citation should be written, formal and address each one of the citation areas, whether or not the facility agrees with the findings.”

Avoid Informal Responses A common error made by many facilities, she said, is sending a response that is too informal. “Many places believe they can send a quick letter and that will be fine. That’s not the case. You need to have documented all your communications with the agency and review your plans for implementation of responses to every violation.

If you’re going to suggest that the pharmacy is exempt from any of [the violations], then you should pull those exemption guidelines and publish references to [them] in your response.”

—Gina Shaw The sources reported no relevant financial disclosures.

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Practical Considerations for

Implementation of Biosimilars in Oncology

DOUGLAS HACKENYOS, PHARMD, BCOP Oncology Pharmacy Clinical Coordinator Department of Pharmacy UConn Health Farmington, Connecticut

T

he FDA approval of filgrastim-sndz (Zarxio, Sandoz) in March 2015 marked a major milestone in drug development—the first agent approved under the Biologics Price Competition and Innovation Act

of 2009.1,2 Since then, 28 more biosimilars have reached the US market.2,3

Although the introduction of additional biosimilars in oncology comes with the hope of significant health care savings, individual institutions are faced with growing challenges related to formulary management.

This article focuses on the practical management and uptake of biosimilars in oncology practice, covering factors related to product selection, information technology (IT) integration, and the role of pharmacist in educating providers and patients about these agents.

Selecting a Preferred Product An immediate issue facing any institution looking to implement use of biosimilars is the selection of appropriate preferred products. Product selection is complicated by the availability of competing biosimilars for any given reference product (Table 1).4-16 Two key

processes are involved in evaluating biosimilar products: clinical review and comparison and pharmacoeconomic evaluation.

CLINICAL REVIEW

AND

COMPARISON

As with any agent being considered for formulary addition, a thorough review of safety and efficacy data is a necessary first step. A unique aspect in reviewing and deciding between biosimilar products is the potential for varying levels of supporting data for each agent. Biosimilars—defined as biologics that are highly similar to and have no clinically meaningful differences

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Table 1. Approved Antineoplastic Biosimilars and Reference Products Reference Product

Biosimilar

FDA Approval Date

Bevacizumab (Avastin, Genentech)

Bevacizumab-awwb (Mvasi, Amgen)

September 2017

Bevacizumab-bvzr (Zirabev, Pfizer)

June 2019

Trastuzumab-dkst (Ogivri, Mylan)

December 2017

Trastuzumab-pkrb (Herzuma, Celltrion)

December 2018

Trastuzumab-dttb (Ontruzant, Samsung Bioepis)

January 2019

Trastuzumab-qyyp (Trazimera, Pfizer)

March 2019

Trastuzumab-anns (Kanjinti, Amgen)

June 2019

Rituximab-abbs (Truxima, Celltrion)

November 2018

Rituximab-pvvr (Ruxience, Pfizer)

July 2019

Rituximab-arrx (Riabni, Amgen)

December 2020

Trastuzumab (Herceptin, Genentech)

Rituximab (Rituxan, Genentech)

Based on references 4-16.

from a previously approved reference product in terms of safety, purity, and potency—receive FDA approval based on analytical studies of structure and function, animal studies, and clinical studies to compare pharmacokinetics, pharmacodynamics, safety, and efficacy end points.17 Depending on the data provided, the FDA may allow extrapolation and approval of indications without additional clinical studies. Although the FDA approval process for biosimilars helps to reduce significant clinical differences between products, pharmacy and therapeutics committees ultimately must choose between products and establish any restrictions on use. In evaluating indications for rituximab products, for example, rituximab (Rituxan, Genentech) and rituximab-abbs (Truxima, Celltrion) carry FDA approvals for rheumatoid arthritis, whereas rituximab-pvvr (Ruxience, Pfizer) and rituximab-arrx (Riabni, Amgen) do not.4-6,16 It is important to consider the patient populations seen at an institution when deciding between products, given potential coverage issues resulting from different approved indications. Additional factors to weigh include the reliability of manufacturers with respect to product quality and availability.

PHARMACOECONOMIC EVALUATION In tandem with any clinical review is the necessary pharmacoeconomic evaluation of available biosimilars.

Historically, average wholesale price is approximately 20% to 30% lower for biosimilars compared with reference products.18 Additional savings may be realized through participation in group purchasing organizations (GPOs). A further benefit of many GPOs is their ability to provide ongoing evaluation of biosimilars and

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coverage considerations, thus shifting some of this process from individual institutions.

Reimbursement factors largely into any biosimilar formulary decision, given that the majority of their use occurs in the outpatient setting. Familiarity with an institution’s payor mix and the formulary preferences of major commercial payors should be weighed heavily in biosimilar implementation decisions. The Centers for Medicare & Medicaid Services (CMS) also has rules to provide financial incentives for use of biosimilars, and many recently approved biosimilars benefit from higher reimbursement than reference products due to 340B pass-through status.19,20 Manufacturer rebates may incentivize some payors to continue to prefer reference products; however, increased market competition with additional biosimilars likely will help increase their uptake.18

IMPLEMENTING BIOSIMILAR USE After selecting a formulary preferred product, full implementation involves IT integration as well as significant provider and patient education. The overall approach to implementation may involve use only in newly started patients or may include conversion of patients already receiving a reference product. Either way, careful coordination with care team members and prior authorization staff is necessary.

MANAGING EXCEPTIONS

AND

CHANGES

The ever-changing landscape of biosimilar approvals and insurance formularies makes it nearly impossible for most institutions to select a single biosimilar to replace any given reference product. Making preferred

Table 2. Reference Products and Innovative Subcutaneous Formulations That Add Competition to Biosimilar Market IV Reference Product

Novel Subcutaneous Formulation

Rituximab (Rituxan, Genentech)

Rituximab and hyaluronidase (Rituxan Hycela, Genentech)

FDA Approval Date

Indication(s)

June 2017

• Chronic lymphocytic leukemia • Diffuse large B-cell lymphoma • Follicular lymphoma

Trastuzumab (Herceptin, Genentech)

Trastuzumab and hyaluronidase-oysk (Herceptin Hylecta, Genentech)

February 2019 • HER2-positive breast cancer, early adjuvant • HER2-positive breast cancer, metastatic

Pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo, Genentech)

June 2020

• HER2-positive breast cancer, early adjuvant or neoadjuvant • HER2-positive breast cancer, metastatic

Based on references 10, 17, and 21-23.

product selection clear across systems may help minimize inappropriate orders and support prior authorization requests; however, a successful biosimilar implementation process will allow conversion to a reference product or non-preferred biosimilar in cases of insurmountable insurance restrictions or rare clinical exceptions. Additional patient-specific exceptions may be required for clinical trials and medications supplied by mail order or specialty pharmacy.

INNOVATION

IN

interchanged the way conventional brand-name and generic medications are. Biosimilar electronic medication records (eMARs) should include the unique NDC, HCPCS J code, generic name (with 4-letter suffix), and brand name associated with each unique product. Comprehensive biosimilar builds minimize look-alike/soundalike (LASA) errors that may arise with order entry, verification, preparation, and administration (Table 3).

LASA warnings also may be added to each build so they appear on the eMAR and drug labels.

REFERENCE PRODUCT LINES

Competition breeds innovation, and this can be seen in additional non-biosimilar products that are poised to draw away from biosimilar use (Table 2).10,17,21-23 Monoclonal antibodies with hyaluronidase intended for faster, more convenient subcutaneous administration are attractive treatment options compared with existing IV reference products and biosimilars.24 These agents have the potential to further complicate inventory management and treatment decisions, but insurance authorization hurdles, site of care issues, and narrower FDA-approved indications hamper widespread use at this time. As more innovative formulations reach the market and lists of approved indications grow, competition with biosimilars undoubtedly will increase.

Biosimilar IT Integration ELECTRONIC HEALTH RECORD BUILD Successful incorporation of biosimilars into the electronic health record (EHR) begins with well-constructed building blocks: electronic prescriptions or medication records. It is important to recognize that biosimilar products have distinct National Drug Codes (NDCs), billing codes, and names that will not allow them to be

BIOSIMILAR ORDER SETS In addition to their many other benefits, electronic order sets and oncology treatment pathways can aid biosimilar uptake substantially. A preferred formulary biosimilar may be set as the default agent in a plan to bolster use and prevent provider confusion at order entry. Statements added to treatment plans and electronic consent forms can be used to further highlight formulary preferences and promote patient education related to biosimilars. Defaulted treatment plans also may assist in streamlining the prior authorization referral process and make the preferred biosimilar selection clear to authorization staff.

Default selection of a preferred formulary product within a treatment plan also must be balanced with a need for flexibility. Ideally, plans should be designed to accommodate third-party payor preferences and nonpreferred products supplied by specialty pharmacies or manufacturer assistance programs. Sophisticated EHRs may allow for toggling between biosimilars and reference products within a treatment plan to allow pharmacist substitution of the required product. Efforts to minimize or avoid use of brand names in oncology treatment pathway titles, plan parameters,

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Table 3. Tips for Minimizing Look-Alike/Sound-Alike Medication Errors With Biosimilars Order entry

• Discrete medication records for each biosimilar with full generic name, 4-letter suffix, and brand name • Default order sets/treatment pathways to formulary product preference

Verification

• Discrete medication records for each biosimilar with full generic name, 4-letter suffix, and brand name • Minimize need for substitution upon verification

Preparation

• Barcode scanning • Segregated inventory locations for reference, biosimilar, and subcutaneous product formulations

Administration

• Barcode scanning • Discrete medication records for each biosimilar with full generic name, 4-letter suffix, and brand name • Segregated inventory locations in automated dispensing cabinets

and other order-set fields outside of the specific medication order may make future substitutions or product conversions more efficient.

DISPENSING TECHNOLOGY Technology within the pharmacy can drastically improve an institution’s ability to incorporate biosimilars into practice. Inventory management systems with electronic barcode scanning can help pharmacy staff differentiate between biosimilars and reference products as soon as medications enter the pharmacy. Biosimilar products may be assigned segregated locations using inventory management technology to avoid confusion during stocking and picking of physical inventory. Barcode scanning, image capturing, and dose compounding verification technology also can minimize preparation errors that may result from LASA biosimilar products.

Dose preparation and verification technology also may help prevent preparation errors that may result from differences in the preparation of specific products. For example, vial sizes, reconstitution instructions, and the need for sterile water for injection (SWFI) versus bacteriostatic SWFI vary between single- and multidose trastuzumab products.15,21 Inventory management and dose preparation may be further complicated by the need to stock multiple biosimilars as well as subcutaneous formulations for any given reference product; barcoding technology is essential to avoid errors in such scenarios.

MEDICATION ADMINISTRATION TECHNOLOGY Technology greatly facilitates safe administration of all medications including biosimilars. The use of barcode scanning and smart infusion pumps can reduce errors that may come with multiple product options.

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Many institutions are opting to minimize build and maintenance work for their smart pump libraries by using a single entry under a generic name to address both reference and biosimilar products with identical administration instructions. Some eMARs also may allow the addition of intranet links to drug information and patient education resources for biosimilar products for easy access at the point of care.

The Role of Pharmacists In Biosimilar Education The continued development and approval of biosimilar agents bring both opportunities and challenges to health care. Biosimilars stand to provide price competition and cost savings sorely needed in cancer care.

Unfortunately, significant knowledge gaps have been identified that add to the challenge of implementing biosimilar use.

BECOMING INFORMED

AS A

PHARMACIST

The rapid introduction of multiple biosimilar agents has challenged all clinicians, including pharmacists, to stay informed. In a 2019 survey conducted by the International Society of Oncology Pharmacy Practitioners, respondents identified 3 key areas that required more training: biosimilar comparative efficacy to innovator products (74%), practical guidance for managing biosimilar conversions (74%), and biosimilar medication safety, including immunogenicity (74%).25 Pharmacists must have a fundamental understanding of biosimilars to be in a position to implement them and educate providers and patients about their use. Numerous review articles, including publications geared specifically toward oncology pharmacists, discuss biosimilars.26,27 Pharmacists also can stay abreast of the most recent

Table 4. Key Patient Counseling Points for Biosimilar Agents What are biosimilars?

• These biologic agents are highly similar to a reference product and are safe and effective.

• Biosimilars are tested and compared with reference products before FDA approval.

• These agents are not generic versions. As biologics, they are large, complicated molecules made by living cells that can’t be copied exactly.

Why use biosimilars?

• These agents provide more treatment options.

• They enhance competition and increase cost savings in health care.

• Biosimilars improve access to care.

• Insurance coverage may require use of biosimilars.

Is it safe to switch to a biosimilar?

• There are no meaningful differences in effectiveness or side effects of biosimilars compared with reference products.

• The function, purity, potency, and immunogenicity of biosimilars are similar to those of reference products.

• Biosimilars use the same dosage and administration as reference products and are produced in FDA-licensed facilities.

• Safety tracking continues after the biosimilar has been approved and reaches the market.

biosimilar approvals through resources such as FDA Alerts and weekly FDA briefings from the Hematology/ Oncology Pharmacy Association (HOPA).28,29

EDUCATING CLINICIANS Several studies have identified areas for improvement in oncology clinicians’ understanding of biosimilars, and pharmacists may play a key role closing these knowledge gaps.30,31 Position statements and resources from the National Comprehensive Cancer Network, American Society of Clinical Oncology, HOPA, and Oncology Nursing Society can be very helpful in supporting pharmacist-led education of clinicians and, ultimately, increasing acceptance of biosimilars.32-35 Educational efforts and identification of a physician to champion biosimilar use can be critical for successful biosimilar implementation.

In addition to clinician education, support staff should be informed about new considerations related to the addition of biosimilars. Pharmacists can facilitate the education of staff involved in patient access and prior authorization by explaining care plan changes, emphasizing changes in preferred products, and providing clinical rationales for biosimilar prior authorizations. Pharmacy technicians also should be educated to minimize the risk for LASA errors in compounding and dispensing.

CURBING BIOSIMILAR MISINFORMATION Given the relatively limited US experience with biosimilars, there may be key concepts that are poorly understood by patients and providers. For example, the term similar may be misunderstood as implying a clinical difference in products rather than its true

intention of emphasizing inherent variability between biologics.36 The abbreviated approval pathway for biosimilars also can be misinterpreted as being more lenient or lax compared to that of reference products.

Pharmacists play an important role in correcting misinformation that might otherwise discourage biosimilar uptake.

EDUCATING PATIENTS Patient education remains a vital component of cancer treatment using antineoplastic biosimilars. The education of patients newly taking biosimilars is comparable to that of other patients initiating treatment with a biologic. Given the growing potential for changing payor and institutional formularies based on cost savings, it may be appropriate to introduce the patient to the term biosimilar and explain key concepts of biosimilar switching, safety, immunogenicity, and production (Table 4).

The massive amount of information that patients must process at the start of a new regimen necessitates succinct, patient-friendly written information.

Biosimilar manufacturers often provide helpful explanations and easily interpreted figures, and these aids can help if branded patient educational materials are permitted at your institution. In addition, the FDA has a host of nonbranded materials with infographics that quickly explain key concepts related to biosimilars in patient-friendly terms.37 Education at the time of conversion from an antineoplastic reference product to a biosimilar is an important, sensitive step to maintain a respectful patient–provider relationship during implementation. Conversions may be driven by institutional

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cost-savings opportunities or insurance formulary preferences; in either case, it is important to be open about the general motivation for increasing biosimilar use. In the outpatient setting, education must be coordinated in advance of order conversion, prior authorization, and eventual treatment with the biosimilar. An example conversion time line may include patient education about the biosimilar in person or via telephone at the time of their treatment with a reference product, prior authorization between treatments, order conversion, and follow-up at the first biosimilar infusion.

Whether patients need to re-consent when converted to an antineoplastic biosimilar is a frequently asked question. Pharmacists can review institution-specific consenting policies and consult in-house legal counsel (if available) to help determine the most appropriate course of action. Either way, it may be appropriate to update consent forms or policies to contain broader wording (eg, “treatment with: X drug and similar products”) to allow for future conversions.

Conclusion Successful implementation of antineoplastic biosimilars requires flexibility in a changing market. Evaluation of clinical data, cost, reimbursement, formulary preferences of major payors, and new innovative formulations is essential for appropriate decision making and product selection. IT systems must be leveraged to further support implementation; comprehensive eMAR builds and technology involved in dispensing and administration will enhance uptake and minimize errors related to biosimilar use. With third-party payor preference being a major factor in determining biosimilar product selection, it is also essential to maintain

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flexibility in eMAR and oncology treatment pathway design. In addition, the incorporation of biosimilars into oncology practice requires education such that everyone involved in the medication use process understands how and when biosimilars are appropriately used. Adequate patient counseling and support when a patient is newly initiated or converting to a biosimilar are critical. Pharmacists are uniquely positioned to provide clinician and patient education and will play a significant role in increasing adoption of biosimilars for cancer treatment.

References 1.

FDA. Drugs@FDA: FDA-Approved Drugs. Filgrastim-sndz.

Accessed October 29, 2021. www.accessdata.fda.gov/scripts/cder/ daf/index.cfm

2.

FDA. Biosimilar product information. Accessed October 29, 2021. www.fda.gov/drugs/biosimilars/biosimilar-product-information

3. FDA. Title VII—improving access to innovative medical therapies.

Subtitle A—Biologics Price Competition and Innovation. Accessed October 29, 2021. www.fda.gov/media/78946/download 4. Rituxan (rituximab) [package insert]. Genentech, Inc; 2012.

5.

Truxima (rituximab-abbs) [package insert]. Celltrion, Inc; 2020.

6. Ruxience (rituximab-pvvr) [package insert]. Pfizer, Inc; 2019.

7.

Avastin (bevacizumab) [package insert]. Genentech, Inc; 2020.

8. Mvasi (bevacizumab-awwb) [package insert]. Amgen, Inc; 2019.

9. Zirabev (bevacizumab-bvzr) [package insert]. Pfizer, Inc; 2019.

10. Herceptin (trastuzumab) [package insert]. Genentech, Inc; 2018.

11. Ogivri (trastuzu-dkst) [package insert]. Mylan; 2017.

12. Herzuma (trastuzumab-pkrb) [package insert]. Celltrion, Inc; 2018.

13. Ontruzant (trastuzumab-dttb) [package insert]. Samsung Bioepis Co, Ltd; 2019.

14. Trazimera (trastuzumab-qyyp) [package insert]. Pfizer, Inc; 2019.

15. Kanjinti (trastuzumab-anns) [package insert]. Amgen, Inc; 2019.

16. Riabni (rituximab-arrx) [package insert]. Amgen, Inc; 2020.

17. FDA. Guidance document: scientific considerations in demonstrating biosimilarity to a reference product. Accessed October 29, 2021. www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf 18. Mulcahy AW, Hlavka JP, Case SR. Biosimilar cost savings in the United States: initial experience and future potential.

Rand Health Q. 2018;7(4):3.

19. Centers for Medicare & Medicaid Services. Fact sheet: final policy, payment, and quality provisions in the Medicare physician fee schedule for calendar year 2018. Accessed October 29, 2021. www.cms.gov/newsroom/fact-sheets/ final-policy-payment-and-quality-provisions-medicare-physicianfee-schedule-calendar-year-2018 20. Centers for Medicare & Medicaid Services. Medicare program: changes to hospital outpatient prospective payment and ambulatory surgical center payment systems and quality reporting programs. Accessed October 29, 2021. www.federalregister.gov/documents/2018/11/21/2018-24243/ medicare-program-changes-to-hospital-outpatient-prospectivepayment-and-ambulatory-surgical-center 21. Herceptin Hylecta (trastuzumab and hyaluronidase-oysk) [package insert]. Genentech, Inc; 2019.

22. Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf) [package insert]. Genentech, Inc; 2020.

23. Rituxan Hycela (rituximab and hyaluronidase) [package insert].

Genentech, Inc; 2017.

24. Anderson KC, Landgren O, Arend RC, et al. Humanistic and economic impact of subcutaneous versus intravenous administration of oncology biologics. Future Oncol. 2019;15(28):3267-3281.

25. Chan A, Patel H, Siderov J, et al. Assessing biosimilar education needs among oncology pharmacy practitioners worldwide: an ISOPP membership survey. J Oncol Pharm Pract. 2020; 26(3 suppl):11-21.

26. Cuellar S, McBride A, Medina P. Pharmacist perspectives and considerations for implementation of therapeutic oncology biosimilars in practice. Am J Health Syst Pharm.

2019;76(21):1725-1738.

27. Foreman E, Chan A, Biosimilars Task Force. Biosimilar implementation in clinical practice: an ISOPP collection for oncology pharmacists. J Oncol Pharm Pract. 2020;26(3 suppl 2).

28. FDA. Get email updates. Accessed October 28, 2021. https://www.fda.gov/about-fda/contact-fda/get-email-updates 29. Hematology/Oncology Pharmacy Association. Drug updates.

Accessed October 28, 2021. https://www.hoparx.org/table/ resources/drug-updates-from-the-fda/ 30. Cook JW, McGrath MK, Dixon MD, et al. Academic oncology clinicians’ understanding of biosimilars and information needed before prescribing. Ther Adv Med Oncol. 2019; 11:1758835918818335. doi: 10.1177/1758835918818335 31. Williamson C, Berger L, Sullivan TP, et al. Addressing oncologists’ gaps in the use of biosimilar products. Am J Manag Care.

2019;25(6 Spec No.):SP188-SP191.

32. Zelenetz AD, Ahmed I, Braud EL, et al. NCCN Biosimilars White Paper: regulatory, scientific, and patient safety perspectives.

J Natl Compr Canc Netw. 2011;9(4 suppl):S1-S22.

33. Lyman GH, Balaban E, Diaz M, et al. American Society of Clinical Oncology statement: biosimilars in oncology. J Clin Oncol.

2018;36(12):1260-1265.

34. Hematology/Oncology Pharmacy Association. Biosimilars issue brief: an important new category of medications for cancer patients. Revised December 2015. Accessed October 29, 2021. http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/ HOPA_Biosimilars_Issue_Brief.pdf 35. Vizgirda V, Jacobs I. Biosimilars: considerations for oncology nurses. Clin J Oncol Nurs. 2017;21(2):E54-E60.

36. Cohen HP, McCabe D. The importance of countering biosimilar disparagement and misinformation. BioDrugs.

2020;34(4):407-414.

37. FDA. Patient materials: biosimilar basics for patients. Updated March 23, 2020. Accessed October 29, 2021. https://www.fda. gov/drugs/biosimilars/patient-materials

Dr Hackenyos reported no relevant financial disclosures.

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Parenteral Nutrition Safety JAY M. MIRTALLO, MS, RPH, BCNSP, FASHP, FASPEN Professor Emeritus The Ohio State University College of Pharmacy Columbus, Ohio Clinical Practice Specialist The American Society for Parenteral and Enteral Nutrition Delaware, Ohio

PHIL AYERS, PHARMD, BCNSP, FMSHP, FASHP Chief Clinical Pharmacy Services Baptist Health Systems Clinical Associate Professor University of Mississippi School of Pharmacy Jackson, Mississippi

P

arenteral nutrition (PN) is a complex therapy that requires a robust system to ensure its safety and efficacy. Since its inception, PN has been associated with serious issues,

ranging from catheter complications, such as thrombosis and infection, to metabolic complications, such as hyperglycemia, refeeding syndrome, and fluid/electrolyte disorders.

Although adverse events (AEs) related to PN rarely are reported, they are likely to be associated with harm when they occur. PN-related mortality has occurred due to contaminated PN admixtures, precipitates of calcium and phosphorus in PN, omission of vitamins from PN (as during a multivitamin shortage in the United States), poorly controlled levels of glucose and electrolytes, and dextrose admixture errors.

PN-specific errors that have been reported to a medication error reporting system, such as Quantros’s MEDMARX, have resulted from performance and knowledge deficits, communication issues, and procedures not being followed. Errors occurred at every level of the PN process, including prescribing, preparation, distribution, monitoring, and evaluation. Early PN AEs led to the recommendation that interdisciplinary teams manage IV catheters in addition to PN.1 Such interdisciplinary care

may help improve the safety of PN. This review aims to: • describe PN as a system of care and identify processes that are prone to error; • provide evidence to explain why PN errors are likely to reach patients and cause harm; • explain the rationale for a standardized process for PN therapy; and • provide resources that every pharmacy/pharmacist can use to evaluate their PN system and resolve potential problems.

The PN System PN, like the medication-use system, is a system of care, the key components of which are assessment, order, order review, preparation, delivery, administration, and monitoring (Figure). The procurement process

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Figure. Parenteral nutrition: a system of care.a a

This process involves multidisciplinary care that incorporates the health-system medication safety system for error reporting.

b

Prescribers include physicians, physician assistants, nurse practitioners, pharmacists, and dietitians.

c

The multidisciplinary team includes a physician, nurse, pharmacist, and dietitian.

ACD, automated compounding device; PN, parenteral nutrition Adapted from: Mirtallo JM. Parenteral nutrition: can outcomes be improved? JPEN J Parenter Enteral Nutr. 2013;37(2):181-189.

(with potential drug shortages and supply chain issues), the nutrition care plan, and transitions of care are components that have an indirect effect on the quality of the PN system. By its nature, PN is an interdisciplinary process involving a dietitian, physician, pharmacist, nurse, and/or patient caregiver. Each of these participants represents a node that can be evaluated in medication safety reviews.

Errors in the PN Process Errors with the PN system have been measured and reported. Sacks et al found the overall error rate to be 74 per 4,730 PN prescriptions (1.6%), or 15.9 errors per 1,000 PN prescriptions filled.2 The majority of errors (39%) were associated with the transcription process,

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a wrong electrolyte dose or salt, the wrong protein source, or the omission of a medication (most commonly insulin).2 The harm score distribution of errors, based on the MEDMARX Database Severity Scale (Table 1), was as follows: 15% “near miss” events (categories A and B), 91% “no harm” events (categories C and D), and 8% “harmful” events (categories E and F). Harmful events included a central PN formulation infused peripherally, PN formulations cycled inadvertently, wrong infusion rates causing severe hyperglycemia (glucose, 500 mg/dL), and incorrect electrolyte salt exacerbating existing metabolic alkalosis.2 This report is important because it demonstrates that PN errors occur within our system and that organizations claiming to have no problems with the PN system

Table 1. MEDMARX Database Severity Scale Severity

Description

A

Circumstances or events that have the capacity to cause error An error occurred:

B

Did not reach the patient

C

Reached the patient but no harm resulted

D

Required monitoring to confirm that it resulted in no harm and/or required intervention to prevent harm

E

May have contributed to or resulted in temporary harm or required intervention

F

Contributed to or resulted in temporary harm and required initial or prolonged hospitalization

G

Contributed to or resulted in permanent harm

H

Intervention required to sustain life

I

Resulted in patient death

Sources: National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) and reference 8.

probably are not looking for them.

In fact, results from a survey by the American Society for Parenteral and Enteral Nutrition (ASPEN) indicate that errors are observed frequently.3 Almost two-thirds of the survey respondents reported observing 1 to 5 PN-related errors per month. Most errors (71%) were related to PN electrolytes. In addition, respondents estimated that 35% of the errors required increased monitoring, 25% resulted in harm, 3.3% were almost fatal, and 1.5% were fatal.3 In preparation for development of the ASPEN guideline,4 Boullata et al conducted a PN-use survey with a section evaluating PN-related medication errors.5 All 895 respondents to the survey, which included dietitians, physicians, nurses, and pharmacists, indicated that they believed PN required a multidisciplinary process, but few reported that they had a PN quality improvement process in place at their institutions (39%).

In organizations that had a process, it was performed by a single department or discipline. In addition, 44% of the respondents reported that their organization did not yet track PN medication errors. Most respondents (58%) also reported that they did not know where in the process errors were occurring.

Mirtallo et al reported on isolated PN errors that occurred between 1992 and 2007 (Table 2).6 This report indicates that there is a low frequency of reported events, but when they occur, they are likely to cause permanent and severe harm, especially in children. PN events occurred across all patient ages and health systems—in hospitals (ICU-medical/surgical units),

extended care facilities, at home, and, importantly, during transitions of care. They occurred as a result of individual error (performance), process issues (preparing PN without having completed training), not using safety alerts in software, and hardware malfunction.

Another source of data on PN errors is the Institute for Safe Medication Practices (ISMP) Medication Error Reporting Program (MERP). Using MERP data, Cohen reviewed the typical PN errors causing severe harm and found the following sources of errors7: • wrong dextrose concentration; • confusion of 5% dextrose with concentrated potassium chloride; • catheter misconnections; • infusion of PN via epidural catheter; and • insulin/heparin additives (due to confusion with units and dosage designations).

The ISMP’s MEDMARX Database Evaluation is another source of information on PN errors. In this national, anonymous, subscription-based medication error reporting system, individuals completing reports describe errors and assign them a severity level (Table 1). The reported errors tend to be low in severity, with no or little patient harm reported.

In 2012, Storey et al evaluated PN errors reported to the MEDMARX system and characterized them by node (process), severity, ingredient, and type.8 The noteworthy findings of the evaluation are shown in Table 3. All PN nodes have errors reported, with errors most frequently occurring during ordering, transcribing, and administration. Each ingredient class is

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Table 2. Selected Serious Events Related to PN System Failures Event

Patient Age

Outcome

Contributing Factors

Calcium/phosphorus precipitation

Adult

Death, respiratory distress

• Improper compounding sequence

Glucose overdose

Pediatric

Death

• Misinterpretation of product label and order

Glucose underdose

Infant

Death

• Final concentration of dextrose compounded as 1.75% instead of 17.5%

Hyperkalemia

Pediatric

Death

• Error in manual preparation of PN

Hypermagnesemia

Neonate

Toxicity

• Compounder malfunction

Iron overload

Pediatric

Liver toxicity

• Misinterpretation of label, 50-fold dosing error

No dextrose in PN

Neonate

Permanent brain damage

• Compounding error

Zinc overdose

Neonate

Death

• Performance deficit; training not completed • Compounder safeguards not used • Dose not assessed for appropriateness

PN, parenteral nutrition Based on reference 6 and ISMP Medication Safety Alert. 2007;12(8):1-4.

involved as well, with the following being most problematic: fat emulsion, electrolytes, and insulin (other).

The most frequent type of error found is omission; it occurs in all nodes but is most often found in ordering and transcribing.8 Common problems leading to these error reports are individual performance factors (competence) or a breakdown in the PN system. In response to PN safety issues, ASPEN developed statements that address competency in PN prescribing9 and PN standardization.10

Product Shortages Affecting PN One variable that has continually affected PN system safety and effectiveness has been PN product shortages.11 PN product shortages highlight the weaknesses in the overall PN system related to inconsistent PN practices. Safety issues related to PN shortages arise from use of a product that is less desirable or familiar, confusion in the prescribing process due to substitution, and frequent changes in compounding and distribution. In addition, workarounds in ordering and compounding processes can circumvent safety checks. Sterility issues occur, especially when organizations repackage lipid injectable emulsions to conserve supply. Accuracy, stability, and compatibility issues also have been reported.11 During periods when supplies were conserved, doses of PN ingredients were reduced and maintained at suboptimal levels, predisposing patients to nutrient deficiencies that required

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increased monitoring (eg, periodic trace element levels).11 The types of PN safety issues related to micronutrients that have resulted from PN product shortages are shown in Table 4.12 Continual PN product shortages over the past 10 years are a barrier to appropriate PN dosing and may lead to nutrient deficiencies and impairment of growth and development.13 The realization that clinicians have not been able to properly dose PN ingredients and adapted the routine practice of underdosing nutrients has led ASPEN to develop recommendations for PN. These include appropriate PN nutrient requirements and dosing recommendations for adult, neonatal, and pediatric patients. Best-practice recommendations are outlined below13: • Do not ration nutrients for PN if the supply of those components is sufficient to provide the full daily dose.

• During component shortages, follow the PN management recommendations available on the ASPEN website at nutritioncare.org/ProductShortage/.

• Return to appropriate dosing as soon as the component shortage has resolved.

• Rationing and conservation strategies are intended to be used only during shortages.

• The lack of observed AEs/deficiencies and the potential cost savings associated with “partial” dosing should not be an impetus to continue less than optimal dosing.

Table 3. PN Errors Reported to MEDMARX by Node and Ingredient Severity, N A-D

Severity, N E-I

Type

Ordering

472

8

Improper dose, omission

Transcribing

360

3

Omission, prepared incorrectly

Compounding

90

1

Deteriorated product, omission

Administration

487

10

Expired drug, deteriorated product, omission

Dextrose

21

3

NA

Fat emulsion

254

3

NA

Electrolyte

92

2

NA

Othera

74

5

Ordering, preparation, and administration

Parameter Node

Ingredient

a

Insulin was the most frequent drug in the ”Other” category related to more harmful events.

NA, information not available Based on reference 8.

Process Standardization for PN Inconsistency in PN practice has the potential to cause PN errors. A factor that contributes to this issue is the inconsistent training of health professionals, including pharmacists, in PN therapy. Mirtallo noted that the number of ways a PN order may be written— based on rate (mg/kg/min), amount (g/kg/d, g/d, g/L), or percent concentration (volume of % original concentration, % final concentration)—can contribute to confusion.14 Best practices provide order templates and expert consensus recommendations for ordering PN.4 However, a survey of practice found poor adoption of best practices.5,15 Boullata et al identified barriers to adopting safe PN practices during the ordering process, with respondents indicating that either a nutrition support team was involved in ordering PN, so a standard process was not needed (33%), or orders were received from multiple facilities, as with home infusion (20%).5 In 2007, ASPEN formed a task force and created a “Statement of Parenteral Nutrition Standardization,” which states that a standardized process may include use of standardized PN formulations (including commercial PN products) but also includes aspects of ordering, labeling, screening, compounding, and administration of PN.10 This important concept was reiterated in the 2014 ASPEN Parenteral Nutrition Safety Consensus Recommendations,16 which emphasize the importance of standardization,

especially during transitions of care. The consensus paper refers readers to additional documents discussing the importance of PN standardization.

Supply Chain Beginning in 2019, PN products began moving through the FDA Unapproved Drug Program. So far, selenium, cysteine, zinc, and ethanol have achieved FDA approval, with other unapproved products being removed. A major issue with this is the sometimesextreme increase in price of the FDA-approved product. This hinders patient access to home PN when providers turn away patients due to lack of reimbursement, providers are unable to stay in the market, or the high-priced product is withheld, putting patients at risk for developing a deficiency. All PN products have already gone through the process and FDA has discontinued the program due to its disruption of the pharmaceutical supply chain. It is never too early to evaluate the safety of PN and develop processes to adequately manage this problem.

New Lipid Injectable Emulsions Soybean oil–based lipid injectable emulsion (ILE), formally known as IV fat emulsion (IVFE), began to be used in the United States in the 1970s. Soybean oil–based ILE was first used in practice to prevent essential fatty acid deficiency, then later incorporated into PN regimens as a source of calories to aid in the

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Table 4. Cases of Micronutrient Deficiencies Resulting From PN Shortages Nutrient

Age, y

Disease/Complication

Cause

Copper

62

Fatigue, poor exercise tolerance, lower extremity edema

Copper intentionally withheld from PN due to shortage

Selenium

2, 3, 4, 5, 13

Biochemical decrease in levels

Selenium intentionally withheld from PN due to shortage

Thiamine

16

Dizziness, vertigo, diplopia, horizontal nystagmus, confusion, and disorientation

Multivitamins inadvertently omitted from PN due to shortage

Based on reference 12.

reduction of carbohydrate load from dextrose.6 It has been the primary lipid used in PN regimens.

Recently, 3 new ILEs have been introduced into the US market. SMOFlipid, a 4-oil emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil17; Clinolipid, a soybean oil/olive oil–based emulsion18; and Omegaven, a fish oil–based ILE.19 These products have been used worldwide and have demonstrated benefits in specific patient populations. However, incorporating these ILE products could create safety issues due to practitioner inexperience. This along with gaps in ILE practice previously identified,20 led ASPEN to publish information on ILE safety considerations.21 The primary medication safety issues related to ILE involve stability, compatibility, in-process or in-use contamination, filtration, and systems issues, especially with prescribing and administration nodes.21 More detailed information may be found on the ASPEN website at https://bit. ly/3kYGlBK. Policies and procedures must be developed if the new ILE products are added to a facility’s formulary.

These products should be filtered using a 1.2-micron filter, and a vented infusion set should be used when Omegaven is infused from the bottle.17-19 Compatibility and stability data associated with soybean oil– based ILE may not be applicable to the newer ILE products. As noted earlier, fat emulsion (lipid) was the most common ingredient associated with PN errors reported to MEDMARX.8

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PN and Electronic Health Records In 2018, ASPEN along with the American Society of Health-System Pharmacists and the Academy of Nutrition and Dietetics published A Call to Action for Optimizing the Electronic Health Record in the Parenteral Nutrition Workflow. This paper identified 5 key areas for optimization of the electronic health record (EHR) in the PN process22: 1. standardized PN order and label; 2. clinical decision support and warnings for macronutrient and micronutrient dosing, toxicity, and incompatibilities; 3. EHR interfaces, interoperability, and workflow involving automated compounding devices (ACD) functionality to improve safety and minimize risk for errors; and 4. ordering cyclic PN, taper up and taper down; and 5. transition of PN from hospital to home or other alternative care settings and vice versa.

The use of the EHR for PN ordering has lagged behind use for other medications. Surveys conducted in 2003, 2011, and 2014 revealed electronic ordering of PN occurred in 29%, 33%, and 63%, respectively. Interface with an ACD occurred in 16% (2003), 19% (2011), and 28% (2014).23 A recent gap analysis conducted by a 22-hospital system revealed the top 5 areas for opportunity for PN and its EHR24:

1. direct transmission of PN orders from the EHR to the ACD without manual reentry; 2. EHR and ACD interfaces that are modifiable simultaneously such that changes to individual product ingredients can be made to reflect availability and/ or conservation; 3. tools within the EHR and ACD to capture failed message transfers; 4. tools within the EHR and ACD to support downtime of the interface; and 5. outsourcing of PN compounding without manual transcription of PN order, supported by the EHR.

PN and Filters In-line IV filters are critical in reducing exposure to particulate matter during the administration of PN. A 2017 ILE survey with gap analysis noted 20.6% of respondents did not filter total nutrient admixtures (TNAs) in adult patients and 18.6% did not filter TNAs in their pediatric population.20 The same survey revealed that 15.1% did not filter ILE infused as a separate infusion in adults. In the pediatric population, 9.7% did not filter, and in neonates, 19.4% ILE infused separately.

ASPEN recently published a position paper updating the use of filters in PN and recommending use of a 1.2-micron in-line filter for administration of TNAs and ILE.25 For TNAs, place the filter as close to the catheter hub as possible. For dextrose-amino acid admixtures, place the filter below the Y-site where the dextroseamino acid admixture and ILE co-infuse. The position paper recommends that health care organizations not filtering PN and ILE reevaluate their decision and consider the potential for increased morbidity and mortality from not using filters.

of transition of care. The ability to use the EHR for safe prescribing of PN continues to evolve, and facilities should work with their vendors to ensure optimization of this process.

References 1.

Maki DG, et al. Ann Intern Med. 1973;79(6):867-887.

2.

Sacks GS, et al. Pharmacotherapy. 2009;29(8):966-974.

3. Seres D, et al. JPEN J Parenter Enteral Nutr. 2006;30(3):259-265.

4. Boullata J, et al. JPEN J Parenter Enteral Nutr. 2014;38(3):334-377.

5.

Boullata JI, et al. JPEN J Parenter Enteral Nutr. 2013;37(2):212-222.

6. Mirtallo J, et al. JPEN J Parenter Enteral Nutr. 2004;28(6):S39-S70.

7.

Cohen MR. JPEN J Parenter Enteral Nutr. 2012;36(2 suppl):14s-19s.

8. Storey MA, et al. Nutr Clin Pract. 2016;31(2):211-217.

9. Guenter G, et al. Nutr Clin Pract. 2015;30(4):570-576.

10. Kochevar M, et al. J Parenter Enteral Nutr. 2007;31(5):441-448.

11. Mirtallo JM, et al. Nutr Clin Pract. 2012;27(3):385-391.

12. Mirtallo JM. Nutr Clin Pract. 2015;30(1):86-91.

13. ASPEN. Appropriate Dosing for Parenteral Nutrition: ASPEN Recommendations. January 2019. Accessed August 12, 2021. http:// www.nutritioncare.org/PNDosing 14. Mirtallo JM. JPEN J Parenter Enteral Nutr. 2012;36(2 suppl):29S-31S. 15. O’Neal BC, et al. Am J Health Syst Pharm. 2002;59(3):264-269.

16. Ayers P, et al. JPEN J Parenter Enteral Nutr. 2014;38(3):296-333.

17. SMOFlipid [package insert]. Fresenius Kabi; 2015.

18. Clinolipid [package insert]. Baxter Healthcare Corporation; 2016.

19. Omegaven [package insert]. Fresenius Kabi; 2018.

20. Christensen ML, et al. Nutr Clin Pract. 2017;32(5):694-702.

21. Mirtallo JM, et al. Nutr Clin Pract. 2020;(35):769-782.

22. Vanek VW, et al. Nutr Clin Pract. 2018;33:e1-e21.

Conclusion The safety of PN is influenced by systems issues related to PN, including errors in the ordering, preparation, delivery, and administration nodes, which can be complicated by supply chain problems with PN products. Health systems need a systematic approach to PN that begins with adequate reporting of and response to errors and includes the standardization of PN processes within organizations and at every point

23. Vanek VW, et al. Nutr Clin Pract. 2016;31:401-415.

24. Ayers P, et al. Nutr Clin Pract. Published online February 2020.

Accessed August 12, 2021. https://doi.org/10.1002/ncp.10463 25. Worthington P, et al. Nutr Clin Pract. 2021;36:29-39.

Additional Resources can be found online at: https://www.pharmacypracticenews.com/Review-Articles/ Article/09-21/Parenteral-Nutrition-Safety/64518

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Medication Errors: The Year in Review

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reventing medication errors is an essential component of caring for patients and must be a core mission of every pharmacy. For medication error–prevention

efforts to be effective, they must be a priority.

An error reduction program begins by establishing a multidisciplinary medication safety team to improve medication use. To be effective, the team must be given reasonable time and resources to assess medication safety and implement systemwide changes that make it difficult or impossible for practitioners to make mistakes that endanger patients. This multidisciplinary team should accept ownership of the medication-use process and enthusiastically embrace the opportunity to improve medication safety. Effective results depend on understanding the entire medication-use process through varied perspectives and disciplines.

The goals of the team should include the following: • Promote a culture of safety to reduce harm from medication errors.

• Increase detection and reporting of medication errors and potentially hazardous drug–use situations.

• Explore and understand the root causes of and factors that contribute to medication errors.

• Educate practitioners about the system-based causes of errors and their prevention.

Horsham, Pennsylvania

• Recommend methods to facilitate the implementation of organization-wide, system-based changes to prevent medication errors.

• Respond to potentially hazardous situations before errors occur.

• Learn from errors occurring in other organizations through the ISMP Medication Safety Alert! and other published reports of medication errors, and proactively take measures to prevent similar errors.

The Institute for Safe Medication Practices (ISMP) is a nonprofit organization that works closely with health care practitioners and institutions, regulatory agencies, professional organizations, and the pharmaceutical industry to provide education about medication errors and their prevention. ISMP independently reviews medication errors that practitioners and patients have submitted voluntarily to the ISMP National Medication Error Reporting Program (ISMP MERP). ISMP is an accessible resource for any pharmacist or organization interested in implementing the actions recommended Text continues on page 42

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Table 1. Safety Issues Related to Labeling, Packaging, and Nomenclature Title

Problem/Discussion Point

Recommendation

Auxiliary label obscures critical reconstitution information on label of REVATIO (sildenafil; Pfizer) oral suspension carton

• An oral suspension of Revatio requires 90 mL of water for reconstitution (60 mL followed by 30 mL).

• A pharmacy technician missed adding the additional 30 mL because an auxiliary label placed on the carton obscured the mixing instructions (Figure 1).

• The reconstitution instructions do not appear on the immediate container.

• Do not obscure important information by affixing auxiliary labels, price stickers, or other labels to medication cartons or containers.

Containers with dual linear barcodes lead to scanning the wrong barcode

• Some IV products have 2 linear barcodes: 1 for the lot number/expiration date and another for the NDC. • If a nurse scans the barcode with the lot number/expiration date, the unsuccessful scan can lead to a delay and calls to the pharmacy.

• If pharmacies are not using the lot number/ expiration date barcode, they should completely block out that barcode on these products.

2

Errors associated with oxytocin use

The following errors have occurred: • Selection of the wrong drug (eg, oxytocin vs oxyCODONE) when searching using only the first 3 letters • Nurse admixture without complete labeling • Infusion bag swaps with magnesium sulfate or lactated Ringer’s, and inconsistent terminology to express the rate of infusion • Lack of clear communication during care handoffs

• Require at least 5 letters of a drug name when searching electronic systems.

• Develop standard order sets and have pharmacy dispense oxytocin in ready-to-administer, labeled bags in standardized concentrations.

• Use barcode scanning technology.

• Standardize oxytocin dosing units and infuse through a smart infusion pump with an engaged drug library.

• Label and trace lines when starting infusions.

• Immediately discard discontinued infusion bags.

• Use communication strategies (eg, SBAR) during communication of care.

1,2,3,5

Generic insulin pen (70% insulin aspart protamine/ 30% insulin aspart) needs to be relabeled

• Generic insulin pen (Novo Nordisk Pharma) for the NOVOLOG MIX 70/30 FlexPen does not specify the insulin ratio on the syringe or carton.

• The 10-mL vial of the generic insulin also does not list the ratio.

• Relabel or add an auxiliary label to note the ratio expression and to note that each 100 units contains 70 units of insulin aspart protamine and 30 units of insulin aspart.

Mix-up between conventional and liposomal formulation of DOXOrubicin injection

• A technician accidentally used liposomal DOXOrubicin (DOXIL) instead of conventional DOXOrubicin (ADRIAMYCIN) for 2 infusions.

• When scanning the barcodes on the vials, the technician received an alert stating, “Wrong medication scanned.”

• The technician overrode the alert, the pharmacist did not catch the error during final verification, and the preparations were dispensed and administered.

• Store vials of liposomal and conventional DOXOrubicin separately with a prominent warning sticker on the liposomal formulation, such as “DOUBLE-CHECK: LIPOSOMAL DOXORUBICIN. DO NOT CONFUSE WITH CONVENTIONAL DOXORUBICIN.” • Ensure dispensing technology requires a second review of scanning overrides.

• Ensure pharmacists are required to perform an independent double check for all drugs and diluents before admixture.

Rocuronium peel-off label (Fresenius Kabi) shows the amount per mL, not per vial

• A peel-off overlay on the label of Fresenius Kabi rocuronium 5-mL vials expresses the concentration as 10 mg/mL, not 50 mg/5 mL. • Reading the peel-off label, staff could mistakenly think that the vial only contains 10 mg.

• Ensure a member of the pharmacy staff removes the overlay before dispensing the vials.

Similarities between B. Braun 500-mL bags of heparin sodium and hypertonic sodium chloride 3%

• ISMP received multiple reports involving look-alike issues between several IV heparin products and IV hypertonic (3%) saline manufactured by B. Braun.

• Use barcode scanning to help prevent errors with these products and store them apart in the pharmacy.

• Consider obtaining one of the products from a different manufacturer.

See KEY on page 42.

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Tech

2,6

Table 1. Safety Issues Related to Labeling, Packaging, and Nomenclature Title

Problem/Discussion Point

Recommendation

Tech

Topical thrombin (RECOTHROM; Baxter) given systemically instead of antithrombin III (THROMBATE III, Grifols)

• A perfusionist looking to administer Thrombate to patient undergoing cardiac surgery typed “T-H-R-O-M” into the ADC. • The perfusionist saw Recothrom pop up on the display screen, selected it in error, and erroneously administered it to the patient.

• Recothrom is supplied with vial-and-syringe packaging that might mislead a practitioner to believe it is a parenteral product when it is actually for topical use only.

• Consider editing product displays in the ADC to clearly indicate “topical thrombin” versus “antithrombin III.” • Implement training for new staff, standardize workflows, and add an independent double check for certain medications.

• Remove topical thrombin products from the ADC and store them in a different location.

• Review the ISMP Medication Safety Alert! Acute Care newsletter from January 12, 2017, for further errors associated with and recommendations for topical thrombin products.

1,2,4

Unsafe expression of strength on Teva vials of haloperidol decanoate injection

• An ADC was almost refilled with 5-mL instead of 1-mL vials of haloperidol decanoate injection.

• Both the 5-mL vial and outer carton labels list the strength per mL (50 mg/mL) rather than prominently noting the total amount per vial (250 mg/5 mL) (Figure 2), as required by USP <7>.

• If a 250-mg vial is needed, purchase it from a different manufacturer until Teva product labeling is updated.

• Ensure barcode scanning of the product occurs when the ADC is refilled.

2,4

Waste and error risk tied to packaging of antineoplastic agent REGORAFENIB (Stivarga, Bayer)

• Regorafenib comes in a carton containing 3 bottles containing 28 (40-mg) tablets for the recommended dose of 160 mg daily for 21 days of a 28-day cycle.

• Reduced dosing (120 or 80 mg) may be required for some patients.

• Tablets must be stored in the original bottle, leading some pharmacies to dispense the full carton; this, in turn, leads to leftover tablets, waste, extra doses, and improper insurance billing.

• Teach patients prescribed lower doses of regorafenib that there will be more medication than needed and instruct them about what to do with leftover medication.

• Provide patients with a dosing calendar for the 4-week cycle that blocks off the final 7 days.

• Patient education material is available from Bayer at http://bit.ly/35AZy3K.

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Table 2. Safety Issues Associated With Order Communication and Documentation Title

Problem/Discussion Point

Recommendation

Tech

Confusion between LYUMJEV and HUMALOG (both insulin lispro

by Lilly), which have different onsets of action

• Lyumjev and HumaLOG are not interchangeable.

• Lyumjev contains ingredients that make it faster acting than HumaLOG. • Dispensing errors have occurred when health care professionals search for either Lyumjev or HumaLOG using only the generic name “insulin lispro” and when they fail to include the brand names on prescriptions.

• Order entry systems and container labels should include both the brand and generic names.

• Practitioners should confirm the brand name if it is not on the prescription.

• Patients should be aware of the differences between these insulins and confirm that they received the correct insulin from the pharmacy.

1,5

Confusion between the numbers 15 and 50

• After talking to an endocrinologist, a medical resident ordered 50 units of insulin glargine for a pediatric patient.

• A pharmacist confirmed the high dose with the resident, although the resident mentioned the endocrinologist seemed tired when they spoke.

• Upon investigation, the endocrinologist stated he ordered 15, not 50, units during the phone consultation.

• When verbalizing medication orders, state the dose the way pilots state numbers (eg, “15 units” stated as “one-five units”).

• Always confirm orders by repeating back the intended dose to the prescriber.

• When possible, remove a mask and face shield when speaking by phone.

5

Nizatidine confused with tiZANidine

• The recall of ranitidine led a hospital to substitute with nizatidine.

• Shortly after, nizatidine was mistakenly prescribed instead of tiZANidine.

• Both drugs have similar letters, with the same last 5 letters (-idine).

• Alert practitioners to the risk for confusion between nizatidine and tiZANidine.

• Use tall man letters when expressing tiZANidine.

• Use barcode scanning during product selection.

1,2

Use brand names to differentiate tacrolimus formulations

• All tacrolimus products were in the same pharmacy drop-down menu.

• Immediate-release tacrolimus was dispensed instead of the extended-release formulation ASTAGRAF XL. • Astagraf XL, ENVARSUS XR, and PROGRAF (and generics) are all different formulations and are not substitutable.

• Display the brand name of tacrolimus extended-release formulations (ie, Astagraf XL, Envarsus XR) on computer screens to help differentiate them from immediaterelease tacrolimus (ie, Prograf, generics).

• Avoid using the modifier “IR” for immediaterelease products.

1,5

See KEY on page 42.

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Table 3. Problems Involving Drug Information, Patient Information, Patient Education, and Staff Education Title

Problem/Discussion Point

Recommendation

Tech

Administer adenosine rapidly for cardioversion

• Adenosine has a very short half-life, requiring rapid administration and subsequent IV flushing to treat life-threatening arrhythmias.

• A nurse administered adenosine too slowly, and the patient failed to convert to normal sinus rhythm.

• Retrieval of adenosine from an ADC often is via override; therefore, instructions for administration built into orders on the MAR may not appear.

• Affix an auxiliary label to adenosine, reminding staff to administer the drug via rapid IV push followed by IV flush.

• Ensure that pharmacy staff and other health care professionals stationed in the emergency department or who respond to codes are aware of the requirement for rapid injection of adenosine and subsequent flush at a site as proximal to the patient’s torso as possible.

4

Education is “predictably disappointing” and should never be relied on alone to improve safety

• Education alone is a weak, low-value improvement strategy.

• Education relies heavily on human memory and vigilance, and ranks among the least effective interventions.

• Unless a knowledge deficit is uncovered, education does little to address human error or policy/procedure violations, or to change unsafe, complex habits.

• A single strategy, particularly one as weak as education, is not enough to change behaviors and prevent errors.

• Numerous high-leverage risk-reduction strategies need to be layered together, on top of education, to create a more robust safety system (Figure 3).

Insulin pens— insulin lispro (HUMALOG) and insulin degludec (TRESIBA) pen mix-ups at home

• Two patients mixed up their insulin pens and gave themselves the wrong insulin, leading to hyperglycemia.

• HumaLOG and Tresiba pens are produced by different manufacturers and have different label colors but are similarly shaped and are a similar shade of blue.

• Patients should be taught different strategies to prevent mix-ups when they use multiple types of insulin.

• Pharmacists can flag the pens with “rapid-acting” or “long-acting” stickers and put the brand name on the sticker to help prevent confusion.

• Once opened and used, the pens no longer need to be stored in the refrigerator and can be stored where they will be administered, as in the bedroom for Tresiba and the dining room for HumaLOG.

Methadone overdose linked to errors in prescribing, dispensing, and administering the drug

• A physician prescribing methadone oral solution 2.5 mg twice daily accidentally selected a 10-mg/mL (concentrated) solution instead of a 1-mg/mL solution.

• Not recognizing that only 0.25 mL would be needed for each dose, the pharmacist dispensed a batched oral syringe (60 mg/6 mL).

• Instead of scanning the patient-specific barcode on the syringe, the nurse scanned the barcode on the outer bag, which failed to warn her to administer only 0.25 mL. • The nurse administered the entire (60 mg/6 mL) syringe, as did the evening nurse.

• Order-entry systems should default to the most appropriate concentration of the product based on the dose.

• Dispense pharmacy-prepared, patient-specific doses for high-alert medications.

• If products must be batched, a single, patient-specific barcode should be available for the nurse to scan at the bedside.

• Standardize batched doses to match commonly prescribed doses in your facility.

1,2,5

Wrong-route tranexamic acid errors

• Three cases of inadvertent spinal administration of tranexamic acid instead of a local anesthetic were reported.

• Prior mix-ups have occurred between tranexamic acid and bupivacaine or ropivacaine.

• All 3 products are available in vials with blue caps, which are often stored upright, making labels difficult to read.

• Typically used in areas where barcode scanning is not used (eg, OR, labor and delivery).

• FDA announced that it will be revising labeling of tranexamic acid to highlight the IV route of administration and strengthen the warning in the prescribing information (http://bit.ly/35FNHS2).

• Purchase these products from different manufacturers to help differentiate their appearance.

• Consider alternate preparations (eg, premixed bag, pharmacy-prepared syringes/infusions).

• Store tranexamic acid separately and avoid upright storage to ensure visibility of labels.

• Use an auxiliary label over the cap to indicate vial contents.

• Use barcode scanning before dispensing or administering.

2,4

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Table 4. Safety Issues Related to Medical Devices and Equipment Title

Problem/Discussion Point

Recommendation

Tech

Bypassing soft low-dose alerts for subtherapeutic heparin infusions

• In a large health system, most heparin infusions required weight-based dosing using a standardized, indication-based protocol.

• A pump programming error resulted in a subtherapeutic dose of 12 units per hour.

• Analysis of aggregate pump data identified 25 similar cases within a 2-month period.

• Users had selected “non–weight-based” heparin in error when programming the pump, and often overrode the resulting low-dose alert.

• Standardize to weight-based dosing for heparin infusions.

• If there are indications for which weight-based dosing is not feasible, limit the non–weightbased programming choice to the established care area/profile where it is needed.

• Establish a hard stop for heparin low-dose alerts.

• Implement smart pump interoperability or employ an independent double check for user-programmed heparin infusions.

3

IV workflow systems can ensure accuracy and prevent errors with CSPs

• When preparing a dose of IV fluconazole for an infant, a technician selected a minibag of potassium chloride (40 mEq/100 mL) that had been incorrectly returned to the fluconazole bin.

• Fluconazole and potassium chloride minibags are similar in appearance.

• The error was caught when the technician went to scan the medication in the IV workflow system before preparation.

• To ensure accuracy during compounding, use IV workflow management systems interfaced with EHR systems.

• Use barcode scanning, as well as imaging and/or gravimetrics.

• Additional recommendations can be found in the ISMP Guidelines for Safe Preparation of Compounded Sterile Preparations (https://bit.ly/3qlqf4m).

6

Keeping infusion pumps outside COVID-19 patients’ rooms

• Many hospitals position infusion pumps outside the rooms of COVID-19 patients to conserve personal protective equipment and reduce staff exposure.

• Hallways may become cluttered.

• Tubing may become disconnected.

• Patient verification during drug administration is a challenge outside the room.

• Medications take longer to reach the patient.

• Tubing may pose a tripping hazard.

• Weigh the risk versus benefit of positioning infusion pumps outside the rooms of patients with COVID-19.

• A special report from ECRI provides guidance on the selection and use of long extension sets for this purpose and factors to consider (https://bit.ly/3qV1ah0).

• Never position pumps in the hallway for 2 patients occupying a single room.

NRFit neuraxial connectors comply with the ISO standard to prevent misconnections

• ISO developed standards to make small-bore connectors for different clinical applications dissimilar to prevent tubing misconnections and wrong-route errors.

• After ENFit ISO-compliant enteral connectors, the next phase is implementation of NRFit, ISO-compliant neuraxial connectors, which are incompatible with the luer system.

• Assemble a team to coordinate transition from the luer connector to NRFit for neuraxial applications.

• Provide education to staff and update related procedures and order sets.

• Review the NRFit Connector Transition Checklist for Nurses and Clinicians (https://bit.ly/3bDfGWC) for further guidance.

1

Primary administration sets for small-volume intermittent infusions can lead to medication loss and underdosing

• Small-volume intermittent IV infusions administered using a primary administration set may leave a significant amount of residual volume behind in the primary administration set, resulting in underdoses.

• The medication left behind in the tubing could become contaminated or unstable over time and/or subsequently be administered with the next patient infusion.

• An appropriate carrier fluid should be added to order sets for small-volume intermittent infusions.

• Increase staff awareness of the residual volume left in the tubing when using primary administration sets for small-volume infusions.

• Create reminders to administer small-volume intermittent infusions with a secondary set.

3

Scanning issues associated with barcodes on curved surfaces

• Scanning difficulties occur when barcodes are placed horizontally on curved surfaces of containers.

• Alert staff to the potential difficulty scanning barcodes on curved surfaces.

• Consider procuring different products with a vertical barcode orientation if these issues could affect patient safety.

2

Set the drug search feature to at least 5 letters in ADCs

• Using only the first 2 or 3 characters to search for a drug in an ADC can lead to errors, especially if the drug is removed via override.

• For example, verapamil or vecuronium may be chosen instead of the intended drug VERSED (former brand of midazolam).

• The Omnicell XT ADC can be programmed to address safety so that at least 5 letter characters must be entered to select a drug via override.

• Determine whether this is a feature that can be implemented based on the ADCs used at your organization.

4

See KEY on page 42.

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Table 4. Safety Issues Related to Medical Devices and Equipment Title

Problem/Discussion Point

Recommendation

Tech

Standardizing critical care drug infusions

• When programming a norepinephrine infusion via a smart pump outside the patient’s room, a nurse accidentally selected a weight-based (mcg/kg per minute) dosing option instead of the prescribed mcg per minute infusion rate.

• The nurse also selected the maximum concentration (32 mg/250 mL) instead of the prepared concentration (4 mg/250 mL).

• Standardize dosing units to either weight-based (mcg/kg per minute) or non–weight-based (mcg per minute) for norepinephrine.

• The ASHP’s Standardize 4 Safety initiative recommends using mcg/kg per minute dosing units for norepinephrine.

3

Use smart infusion pumps with DERS in the OR

• Use of smart pumps with DERS in the OR by anesthesia providers is often limited.

• A recent analysis of anesthesia providers using smart pumps showed frequent programming of propofol and dexmedetomidine in excess of labeled dosing for an hour or more.

• Dose excursions likely are caused by providers not using the pump’s bolus-dose feature and a lack of hard stops in anesthesia mode.

• The use of smart infusion pumps with an engaged drug library should be expected in the OR. • Engage anesthesia providers in the building of the smart pump library.

• Implement upper and lower dose limits.

• Restrict use of pumps in anesthesia mode.

• Require the use of the pump’s bolus feature.

• Train anesthesia providers to use smart pumps with DERS, including the bolus feature.

• View ISMP’s guidelines on smart pumps for more information (http://bit.ly/39tTDPk).

3

Using smart infusion pumps incorrectly in the OR leads to milrinone overdose

• An anesthesia resident started a milrinone infusion in the OR using a smart pump in “anesthesia mode.”

• Concentration was entered as 200 mcg in 100 mL, when the Hospira premixed infusion being hung contained 20 mg in 100 mL. • The bag label emphasized the per-mL amount (200 mcg) rather than the total drug in the bag (20 mg) (Figure 4).

• Rapid infusion and overdose occurred, requiring ICU monitoring.

• In addition to the previously mentioned recommendations, hands-on education about how to use smart pumps along with competency assessments should be implemented for all anesthesia providers.

3

Ventilator arms may break from the weight of hanging 2-L bags of sterile water

• Hanging a 2-L bag of sterile water for humidification on the articulated arm of a ventilator may cause the arm to break due to the weight of the bag.

• Similar concerns have been reported with 1-L bags of sterile water, which also may be inadvertently infused as IV fluids.

• Use hard-sided sterile water containers to differentiate them from IV fluids.

• Avoid using 1-L sterile water bags outside the pharmacy because they look too similar to IV bags (Targeted Medication Safety Best Practice #10) (http://bit.ly/35FPlDh).

• Instead of hanging a bag from a ventilator arm, use a pole labeled “For Respiratory Use Only.”

Table 5. Other Discussion Items Title

Problem/Discussion Point

Recommendation

Tech

Differences between human error, at-risk behavior, and reckless behavior

• Many organizations struggle with differentiating and responding justly to human error, at-risk behavior, and reckless behavior.

• Human error is inadvertent.

• At-risk behaviors occur when staff knowingly violate policies and procedures because they have lost the perception of risk or believe the risk to be insignificant or justified.

• Reckless behavior is the conscious disregard of what is known to be a substantial and unjustifiable risk.

• In a just culture, human error is managed by consoling the person who made the error and redesigning the system to make it less prone to human error.

• At-risk behavior is managed by coaching the person who made the error to recognize the risk, redesigning the system, and using a reward system that encourages safe behavior.

• Reckless behavior is managed through disciplinary actions.

• Safety programs should focus on the just and proactive management of at-risk behaviors, not just the management of human error and reckless behavior.

Doubleconcentration (2%) propofol now available

• There has been a shortage of propofol 1% (10 mg/mL) DIPRIVAN and generics.

• Fresenius Kabi received an EUA from the FDA to import propofol 2% (20 mg/mL) Fresenius PROPOVEN emulsion in 100-mL vials.

• Alert practitioners to the double concentration.

• Post a wall chart and distribute fact sheets for health care providers and patients/caregivers.

Table continues on following page

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Table 5. Other Discussion Items

continued

Title

Problem/Discussion Point

Recommendation

Errors in paramedicine (prehospital care delivered through EMS)

• Rapid changes in ill or injured patients present challenges that increase the risk for medication errors.

• EMS errors are related to common themes: – Clinical assessment and management errors – Therapeutic product use errors – Errors in communication during transitions of care – Errors related to inventory management

• When stocking EMS vehicles or aircraft, choose products that do not look alike and are ready to administer in standard concentrations.

• Stock medications with the front label facing outward.

• EMS providers should get a complete medication history from each patient and communicate that to the provider at the transition of care.

• Use standardized checklists for verbal handoffs.

Errors with remdesivir (VEKLURY, Gilead)

• To treat severe COVID-19, FDA issued an EUA for remdesivir, which is supplied in 100-mg/20-mL (concentrated solution) and 100-mg (lyophilized powder) vials.

• Incorrect storage and preparation of both formulations have led to wrong dose or formulation errors or discarding of improperly prepared/stored products.

• Review details about correct dosing, administration, preparation, and storage in the prescribing information for remdesivir (https://bit.ly/3mcNT19).

• Use standardized order sets, alerts, and/or a hard stop to enter patients’ weights.

Inadvertent IV administration of an oral liquid medication

• A nurse prepared oral liquid midazolam in an oral syringe.

• A medical resident verbally checked the drug name, expiration date, dose (based on patient weight), and volume before taking the unlabeled syringe to the procedure room.

• The physician began to administer the medication via IV push and asked for the medication to be put in a “normal” syringe.

• Wrong route error was discovered after nearly half of the dose had been wrongly administered IV.

• Separate different formulations of the same medication in storage areas.

• Label medications prepared in syringes unless they are immediately administered.

• Ideally, the person preparing the medication should be administering the medication.

• Educate clinical staff on how to prevent wrong-route administration of medications, including the appropriate use of oral/enteral syringes.

Leadership support is vital during the COVID-19 pandemic

• Health care workers continue to work in under-resourced environments and deal with the risk for infection during the COVID-19 pandemic.

• Leadership is vital in supporting staff wellbeing, health, and safety.

• Half the respondents to a recent survey strongly agreed that their employers have communicated a clear plan of action for COVID-19.

• One in 3 respondents are confident that they will be safe if they follow their organization’s policies during this crisis.

• Leaders can support staff by: – creating a safe haven for staff to retreat, reflect, and talk to each other away from their work units; – creating an environment of trust, fairness, and compassion; – balancing critical information with positive updates; – communicating transparently; and – being a visible leader in patient care units.

Test patients should not be created in live EHRs

• At the request of a surveyor, a nurse ordered alteplase for a test patient.

• This test patient was accidentally “admitted” to a different hospital within the system.

• The alteplase was almost prepared for a real patient; however, the pharmacist questioned the real patient’s nurse about the dose.

• The nurse reentered the order, believing it had been ordered incorrectly; however, the physician never intended for the real patient to receive alteplase.

• Use a test environment, not a live EHR, to create test patients.

• If creating a test patient in a live EHR is necessary, use an obviously fake name (eg, “Test Patient”).

• Do not allow one hospital to impact the workflow of another hospital within the same health system.

• Provide staff with clear instructions and procedures to follow when demonstrating workflows to surveyors.

See KEY on page 42.

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Tech

1,5

Table 6. ISMP’s Targeted Medication Safety Best Practices for Hospitals Title

Problem/Discussion Point

Recommendation

Tech

FDA removes syringe administration from vinCRIStine labeling

• More than 140 deaths have occurred worldwide from accidental intrathecal injection of vinCRIStine via syringe.

• No cases have been reported with dilution of the drug in a minibag.

• In 2019, ISMP called on FDA to eliminate vinCRIStine syringe administration in official product labeling.

• In June 2020, FDA asked Pfizer to revise product labeling.

• Pfizer revised the package insert so all references to preparation and administration in an IV syringe have been removed.

• VinCRIStine should always be diluted in a flexible plastic container and prominently labeled as indicated: “FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES.”

6

FDA revises labeling for methotrexate tablets

• ISMP has received numerous reports about fatal oral methotrexate errors occurring when the weekly dose was divided into 3 doses given 12 hours apart but mistakenly taken daily every 12 hours for numerous days in a row.

• FDA has required the removal of divided doses from official labeling.

• Official labeling now recommends a single weekly dose for nononcologic indications.

• Inform staff about this change and make sure any patient educational materials reflect this change.

Inappropriate prescribing of transdermal fentaNYL patches for opioid-naive, elderly patients

• FentaNYL patches have been inappropriately prescribed for opioid-naïve, elderly patients discharged from the ED to treat acute pain or due to an “allergy” to codeine that was only a minor drug intolerance.

• Prescribing information recommends that fentaNYL patches be used only in opioid-tolerant patients for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment.

• Document each patient’s opioid status.

• Build interactive alerts to confirm opioid tolerance when prescribing fentaNYL patches.

• Distinguish between true allergies and drug intolerances when collecting allergy information.

• A Risk Evaluation and Mitigation Strategy for long-acting opioids strongly encourages practitioner training about safe use of opioids.

1,5

Prepare for vials of neuromuscular blocking agents without cap warnings through 2022

• Shortages of neuromuscular blocking agents occurred due to the high demand for treating COVID-19 patients.

• FDA allowed temporary manufacturing of these agents without the vial cap (seal) warning statement, “Paralyzing Agent,” as normally required by USP and FDA (Figure 5).

• The absence of this warning may lead to potentially fatal drug selection errors.

• Affected products include vecuronium bromide (Fresenius Kabi) and rocuronium bromide (Athenex and Alvogen) vials.

• These products are no longer being manufactured, but current manufacturer expiration dates extend through June 2022.

• Alert staff about the absence of the usual warning statement on some of these vial caps.

• Store the vials lying down with the label facing up (not cap up).

• Affix auxiliary labels noting, “Warning: Paralyzing Agent,” to vial caps.

• Use barcode scanning during preparation and administration.

• For additional strategies, go to http://bit. ly/3qV38xU.

2,4

Two new best practices in the 2020-2021 TMSBPs for Hospitals

• The TMSBPs consist of 16 best practices.

• New #15: Verify and document patient’s opioid status before prescribing and dispensing certain opioids.

• New #16: Limit the variety of medications removed via override from an ADC; require an order before removing medications from the ADC; monitor ADC overrides; and periodically review medications available via override.

• Refer to ISMP’s TMSBP FAQs (https://www. ismp.org/tmsbp/faq) and Implementation Worksheet (http://bit.ly/3svlmbd) for help implementing these best practices.

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Figure 2. Unsafe expression of strength on Teva vials of haloperidol decanoate injection.

Both 1-mL and 5-mL vials of haloperidol decanoate are labeled as 50 mg per mL. The 5-mL vial should prominently note the total amount per vial (250 mg per 5 mL) as required in USP Chapter <7>.

Figure 1. Auxiliary label obscures critical reconstitution information on REVATIO (sildenafil) oral suspension carton label.

Auxiliary pharmacy labels obscured a portion of the reconstitution directions for Revatio oral suspension.

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Figure 3. Education is “predictably disappointing” and should never be relied upon alone to improve safety.

Categorization of safety strategies as most effective but hardest to implement (top) versus the least effective but easiest to implement (bottom).

Figure 4. Incorrect use of a smart infusion pump in the OR leads to milrinone overdose.

Hospira’s premixed milrinone lactate injection label contributed to a pump programming error because of the emphasis on 200 mcg per mL, not 20 mg/100 mL.

Figure 5. Prepare for vials of neuromuscular blocking agents without cap warnings.

Images of currently approved cap (left) and temporary cap (right) for rocuronium bromide injection, 50 mg per 5 mL and 100 mg per 10 mL.

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KEY Identified issue involves a medication listed on ISMP’s List of High-Alert Medications in Acute Care Settings (http://www. ismp.org/Tools/institutionalhighAlert.asp). High-alert medications are associated with a heightened risk for causing significant patient harm when they are used in error.

ADC, automated dispensing cabinet; CPOE, computerized prescriber order entry; CSP, compounded sterile preparation; DERS, dose error-reduction system; EHR, electronic health record; EMS, emergency medical services; EUA, emergency use authorization; IM, intramuscular; ISO, International Organization for Standardization; IT, information technology; MAR, medication administration record; NDC, National Drug Code; OTC, over-the-counter; SBAR, situation, background, assessment, recommendation; TMSBPs, targeted medication safety best practices

TECHNOLOGY (TECH) KEY

1

A fully integrated CPOE system includes the capability to build medication safety alerts and clinical decision rules. It should directly interface with the laboratory system and pharmacy, list drug–drug and drug–disease interactions, and offer clinical decision support.

4

ADCs are robust, point-of-use dispensing systems. ADCs should

2

Barcode-enabled point-of-care systems are designed to detect medication errors during medication distribution and/or administration.

Using a barcode scanner to scan barcodes on a medication and a patient’s wristband, users can verify and record all drugs administered to the patient.

5

A “robust” pharmacy order entry system is fully interfaced with a

3

“Smart” infusion pump systems allow users to enter drug infusion

6

IV workflow technology combines software and automated pharmacy workflow technology for compounding sterile products. It receives dose information from health IT systems and uses robotics, gravimetric analysis, and barcode scanning with video technology or digital images. Some systems can generate drug-specific administration notes and labels for point-of-care scanning by nurses.

protocols into a drug library with predefined dose limits. If a dose is programmed outside established limits or clinical parameters, the pump halts or sounds an alarm. Some pumps can integrate patient monitoring and other patient parameters.

Text continued from page 31

herein. Among the many products and services ISMP offers is ISMP Medication Safety Alert! Acute Care, a biweekly newsletter that provides timely information related to error prevention. It identifies errors that have been reported by organizations and offers recommendations to prevent those errors from recurring.

The information in the tables of this review summarizes many of the significant error-prevention strategies recommended in the ISMP Medication Safety Alert!

Acute Care newsletter from January through December 2020. The errors presented in the tables are actual or potential errors reported to ISMP. Each table consists of 4 columns. The first column lists the involved medications, devices, or other problematic issues. The second column describes the specific error or problem.

The third column contains ISMP’s recommendations to proactively address similar errors and prevent them from recurring. The fourth column lists technology that may help prevent or detect such errors. Technology can be a powerful tool in the fight against medication errors but only when it is used appropriately within a

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be integrated with the health care facility’s information system and directly interface with the pharmacy system. In addition, ADCs must be able to use barcoding technology for the restocking process to prevent medication errors.

CPOE system and must be able to produce medication safety alerts, directly interface with a health care facility’s information systems, and generate a computerized MAR to be used by nurses while they administer medications.

well-designed medication-use system.

The technology key summarizes the technology addressed in the tables and specific criteria that ISMP believes should be included.

Suggested Reading Cohen MR, ed. Medication Errors. 2nd ed. American Pharmacists Association; 2007.

Institute for Safe Medication Practices. ISMP Medication Safety Alert!

Acute Care newsletters 2020. Accessed January 11, 2021. www.ismp. org/newsletters/default.asp Institute for Safe Medication Practices website. Accessed January 11, 2021. www.ismp.org

Compiled by ISMP and FDA/ISMP Safe Medication Management Fellows.

2019-2020: Benedicta Asamoah, PharmD; Allison Hanson, PharmD, BCPS; Neha Kumar, PharmD; Yashar Rafi, PharmD; Nistha Shah, PharmD. 2020-2021: Merissa Andersen, PharmD, MPH; Damon Birkemeier, PharmD; Bennet Ninan, PharmD; Jill Paslier, PharmD, CSP.

PRINTER-FRIENDLY VERSION AVAILABLE AT PHARMACYPRACTICENEWS.COM

IV-WMS: Slow Adoption Continues to Threaten Compounding Safety

A

lthough the COVID-19 pandemic continues to strain budgets and resources, U.S. hospital

pharmacies have made progress in adopting IV workflow management systems (IV-WMS), which pharmacy leaders say are critical to improve the safety and efficiency of IV drug compounding.

Still, progress is slow. With a minority of hospitals using IV-WMS, advocates are questioning why the technology remains so underused despite years of guideline recommendations and robust evidence of its benefits.

“Why aren’t IV workflow systems in every hospital in the country?” asked Christopher R. Fortier, PharmD, the chief pharmacy manager at Massachusetts General Hospital (MGH), in Boston, during Illuminate 2021, Omnicell’s digital medication management conference. “Adoption is really low. It boggles my mind. This technology has been around for 10 or more years, so why [the delay]?”

Several factors may contribute to the low rate of adoption, but Dr. Fortier’s theory is that hospitals were incentivized to focus on implementing electronic health record (EHR) systems when IV-WMS first hit the market. “I think IV workflow got put on the back

burner,” he said. But he and many of his colleagues hope that change is on the horizon.

The most recent national practice survey by ASHP found about 21% of U.S. hospitals used IV-WMS, a 1% increase from the previous year (Am J Health Syst Pharm 2021;78[12]:1074-1093). For comparison, the rate was 13% in 2017. “Fortunately, we’ve had a little bit of a push, but there’s still a long way to go,” Dr. Fortier said.

Many hospitals have at least adopted key components of IV-WMS, such as barcode scanning (33.8%), image verification (25.3%) and gravimetrics (5%), and small numbers reported the use of robotics (3.4%), said Amey C. Hugg, BSPharm, ASHP’s director of member relations for the Section of Pharmacy Informatics and Technology.

“When all technologies are considered, … 52.7% of hospitals do not use any technologies for compounding sterile preparations, which is decreased from 2017,

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10 Tips for Implementing an IV-WMS B lake Barlow, PharmD, MBA, MS, the clinical pharmacy manager for adult medicine and cardiology at WVU Medicine, in Morgantown, W.Va., and Andrew C. Lodolo, PharmD, BCPS, BCCCP, the pharmacy manager for inpatient services at Eskenazi Health, in Indianapolis, shared key lessons they learned when implementing an IV-WMS at their institutions: Involve staff early. Dr. Barlow recommended that pharmacists and technicians be integrated into the process as early as possible so they know what the device is, how it works and why it’s important for patient safety. “We saw that if you’re not integrating early, you might see some failures down the line due to [lack of] staff buy-in.”

Train support staff. Use training and education resources to develop pharmacist and technician subject-matter experts to provide ongoing support to staff and management, Dr. Barlow said.

Maintain existing systems as a backup. It’s important to maintain operation of your existing compounding workflow as a safety backup during early implementation.

Dr. Barlow noted that a staff member “might get confused on how to proceed, or if there’s a tech error up front, you need a safety system to fall back onto so a patient can get the right medicine as quickly as possible.”

Share progress. “We utilized an implementation daily go-live project dashboard that we found very successful to really promote our progress with the group, cheer them on, show them our success … so that everybody was kept in the loop on a daily basis as far as how well we were going with the process,” Dr. Barlow said.

Decrease batch time intervals.

Dr. Barlow said his institution plans to reduce batch times so staff can focus on a smaller volume of orders. “With a brand-new device, we found that the staff were getting a little overwhelmed when a lot of batch orders were printing out at once. Even though those orders might not be due for four to five hours, just the sheer volume that was sitting next to them maybe made them feel a little stressed and try to rush the process.”

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Identify key stakeholders up front. Dr. Lodolo emphasized the importance of aligning key stakeholders at the beginning of the product selection process. “We identified key stakeholders who would be needed to weigh in on this decision of implementing an IV workflow solution that included: 1) senior leadership that would provide the financial backing for this initiative, 2) pharmacists, both front-line and those who would maintain the system, and 3) IT [information technology] team members, as we knew we wanted an integrated system, and our EHR specialist,” he said. “At golive, we knew it would be important to identify other key stakeholders like subject-matter experts and super users.”

Release medications in phases.

Dr. Lodolo said he “was really hopeful for a big bang go-live … for all compounded sterile products.

Unfortunately, that wasn’t an option.

Therefore, we introduced biweekly phased releases of two to four medications into production. This allowed for staff buy-in because they were still able to use the systems that they were comfortable with.”

Create and maintain a test environment. A test environment

is something Dr. Lodolo recommended for any health system planning to implement an IV-WMS. “This allows us to develop protocols in a safe space and complete robust testing before we implement that into the production environment.”

Use protocol selection.

Dr. Lodolo recommended using gravimetric verification whenever possible, especially for products with patient-specific dosing, such as high-alert medications or partial vials.

For whole vials, “we might implement volumetric workflows because we know you’re going to typically use the whole vial, so there’s no reason to slow down the process if you don’t have to.”

Develop a synced cadence.

Dr. Lodolo’s institution developed a synced cadence as “a tryout approach with our operations team, our EHR analytics team and our IV-WMS consulting team. This has allowed for robust evaluation of ordering capabilities within EHR to make sure all orders transition to IV-WMS appropriately. It also allows us the opportunity to troubleshoot protocols before they go into the production environment.”

—A.L.

‘IV workflow management systems, technology and automation are proven to improve patient safety by reducing potential for human error associated with manual processes. Use of such technologies is strongly advocated by ASHP and the Institute for Safe Medication Practices.’

—Amey C. Hugg, BSPharm

when 64% of hospitals did not use any technology for sterile product compounding activities.”

Delay Despite Society Support The slow rollout has occurred despite societies of pharmacy recommending the use of IV-WMS for more than a decade. That’s an unfortunate delay, Dr. Hugg noted. “[IV-WMS], technology and automation are proven to improve patient safety by reducing potential for human error associated with manual processes,” she said. “Use of such technologies is strongly advocated by ASHP [bit.ly/3j68Wn3] and the Institute for Safe Medication Practices [ISMP; bit.ly/3nrdkhN].”

The risks for human errors in manual preparation of IV medications are well established. A 2020 ISMP survey showed 74% of pharmacy staff were aware of at least one compounding error, most of which were incorrect doses (58%), during the previous 12 months (bit.ly/3jhGC17).

The benefits of IV-WMS in reducing these errors also are well established, said Dr. Fortier, noting a halfdozen studies published in the American Journal of Health-System Pharmacy over the 2010s that all demonstrated “a major amount of error detection” using IV-WMS, as well as staff satisfaction.

IV-WMS Versus Barcoding A team at MGH demonstrated the benefits of implementing an IV-WMS in a recent study, according to Blake Barlow, PharmD, MBA, MS, a former resident at the hospital and now the clinical pharmacy manager for adult medicine and cardiology at WVU Medicine, in Morgantown, W.Va. Unlike studies that compare IV-WMS with manual processes such as the syringe pull-back method, Dr. Barlow and his colleagues compared an IV-WMS (Omnicell IXV) with its existing barcode system (Epic Dispense Prep/Check) after implementation across MGH’s entire nonhazardous formulary (five sterile compounding suites, two off-site infusion pharmacies, 350,000 IV doses dispensed annually, 21 technicians and nine pharmacists).

Using failure modes and effects analysis, Dr. Barlow and his colleagues found the IV-WMS significantly

reduced the potential for errors, particularly in the technicians’ compounding workflow, with a 53% reduction (P=0.02). The IV-WMS also reduced the risk for severe errors in the technicians’ workflow by 81% (P<0.001).

“Not only did it provide a much safer environment for our patients,” Dr. Barlow told attendees at Illuminate 2021, “the staff as a whole—both pharmacists and technicians—actually preferred the use of the device, perceiving it to be both safer and more accurate.”

However, total turnaround time increased by about five minutes (24.6 vs. 29.6 minutes), with a longer compounding process (15.4 vs. 22.2 minutes) and slightly shorter verification (9.2 vs. 7.4 minutes).

Slower Turnaround Times Are a Trade-off for Safety Concern about longer turnaround times is understandable, but slower turnaround is a trade-off for improved safety, according to Dr. Fortier. “It primarily will slow down the technician,” he said. “But that’s the give-and-take of having a much safer situation. On the flip side, it will improve the efficiency of the pharmacist verification because … it can be done remotely [and there will be] better information for that pharmacist to verify those medications.”

Beyond turnaround, the cost of implementation is perhaps the most commonly cited barrier to adoption of an IV-WMS. But as previously reported, research has shown the potential cost savings of this technology can offset the up-front investment. One study of IV-WMS implementation at Cincinnati Children’s Hospital showed the system significantly reduced medication waste (P<0.001) and projected more than $500,000 in annual savings (Int J Med Inform 2018;115:73-79).

A New Standard of Practice Christina Michalek, BSPharm, RPh, a medication safety specialist and an administrative coordinator for the Medication Safety Officers Society at ISMP, noted that the up-front investment barrier could be mitigated if an IV-WMS were to become a required standard of practice. “It’s not required, and unlike other technologies like CPOE [computerized provider order entry] and BCMA [barcode medication administration], it is

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‘[IV-WMS is] not required, and unlike other technologies like [computerized provider order entry] and [barcode medication administration], it is not incentivized.’

—Christina Michalek, BSPharm, RPh

not incentivized,” she said.

The recently released update to USP Chapter <797> guidelines for compounding sterile preparations does not include requirements for an IV-WMS (bit.ly/3lL6949).

Navigating Vendor Selection Another challenge can be selection of a vendor when adopting an IV-WMS. To help evaluate product features, Dr. Fortier recommended THRIV Coalition’s technology checklist for five standard capabilities an IV-WMS should have (www.thrivcoalition.org/technology-checklist/). The criteria are: • interfaced software that guides staff step-by-step through the compounding process; • barcode scanning; • volume verification using images, gravimetrics or volumetrics; • auto-labeling; and • auto-documentation.

All these and other barriers to adoption disproportionately affect smaller institutions, which explains

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why their adoption rates are lower, Ms. Michalek noted.

“Smaller hospitals definitely have unique challenges, especially with financial and human resources,” she said.

‘Stay Committed’ Ms. Michalek encouraged pharmacy leaders to remain dedicated to improving safety through IV-WMS adoption despite these obstacles. “If you are struggling with gaining support, stay committed,” she said.

“If you’ve gotten support for acquisition of sterile compounding technology and are beginning implementation, leverage resources from your peers, vendors, national organizations and ISMP’s forthcoming guidelines. We hope the upcoming guidelines will drive more discussions related to the need for technology in sterile compounding as well as draw attention to the best practices for their use.”

—Adam Leitenberger

The sources reported no relevant financial disclosures other than their stated employment.

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