CASE STUDY
www.baxter.com
INTENDED OUTCOME
The right drug with the right diluent for the right dose at the right
time has been and remains the ever-present responsibility of a
pharmacist. The introduction of IV Workflow Management systems
(IVWFM) into the sterile compounding space has significantly
reduced the effort and improved the chances of consistently
meeting this responsibility. This type of quality assurance
verification has been the primary use of IVWFM systems since
their introduction into the United States in 2008 when DoseEdge
Pharmacy Workflow Manager system (DoseEdge) was introduced.
However, the pharmacist’s responsibilities continue to grow
with the increasing number and ever more strict regulations
and guidelines governing the processes for compounding
sterile preparations and the environments they are prepared
in. Therefore, pharmacists must consider how these
IVWFM systems can be used to support these needs.
CHALLENGES
Accurate and consistent data from published literature on the
incidence of IV compounding errors is difficult to find as most
facilities and pharmacists are reluctant to share this type of
information. Confounding this is the fact that there is no single
recognized definition of what constitutes these types of medication
errors. The relatively small number of data sets that are available for
error rates at individual facilities or groups of facilities not using
any type of IVWFM system (or technology-assisted workflow
systems) can range from 0.22%1 to 9%2. These errors can
result from pharmacy staff not knowing with specificity
what drugs, diluents, and volumes should be used to
prepare a compounded sterile preparation (CSP).
Before automation, pharmacists had to verify
every CSP dispensed from the cleanroom
using manual and sometimes inexact
methods. It was not always possible
to determine if the correct drug
and/or amount was added to
an IV container. Therefore, the true number of compounding errors
could not be determined.
The Institute for Safe Medication Practices (ISMP) published a
survey in October of 2020 that included 634 respondents, 80%
of whom were pharmacists, and another 18% were pharmacy
technicians3. The survey results demonstrated some
concerning results3:
• 56% of all responders (355) reported always having and following
standard operating procedures for the compounding process.
• 48% of pharmacist responders (243) stated that it was always
easy to identify with certainty which drugs, diluents, and
volumes were used when verifying the preparation of a CSP.
• 57% of respondents (361) were using technologies
to support sterile compounding.
• 47% of the 361 respondents using technology (170) were
taking advantage of IVWFM systems that included both
barcode scanning and image capture to help manage risks.
Additionally, on November 1, 2022, the United States Pharmacopeia
(USP) published the revised General Chapter <797> Pharmaceutical
Compounding — Sterile Preparations (USP <797>) which
provides the new minimum acceptable standards for sterile
compounding. In recent years, USP <797> requirements seem
to also be garnering more attention from organizations such
as The Joint Commission and other accrediting bodies which
now conduct inspections according to these requirements.
Many of the updates to USP <797> are relatively minor changes, and
the basic principles remain the same. Examples of this are the need
to maintain acceptable levels of viable and non-viable particle counts
in the classified areas. However, more detail is provided around the
performance and frequency of the required sampling. These changes
in testing detail don’t affect the basic requirements of how many
particles per cubic meter or colony forming units per cubic meter
are acceptable as those limits are set by separate ISO standards.
However, as with previous revisions of the chapter, some changes
in the guidelines are more significant and may require considerable
INTO THE FUTURE WITH BAXTER’S
DoseEDGE PHARMACY WORKFLOW
MANAGER SYSTEM
Sponsored by an Educational Grant From Baxter
CASE STUDY
www.baxter.com
changes to pharmacy and cleanroom operations. An example of
this type of significant change would be how restricted-access
barrier systems (RABS) can be used. In the 2008 version of the
chapter, the ISO 5 environment that can be achieved with these
systems alone was considered sufficient to apply extended Beyond-
use Dates (BUDs) for CSPs regardless of where the RABS was
located4. However, the 2023 version of USP <797> requires that
the RABS be located in an ISO 7 environment to apply Category
2 or 3 beyond-use dating5. Essentially, a RABS in an unclassified
space is now equivalent to a segregated compounding area.
In any case, whether the standards of the 2008 and 2023
versions of the chapter remain the same, or they receive minor or
significant updates, history tells us that they can be challenging
to consistently adhere to for many pharmacies. In the 2023
State of Pharmacy Compounding survey published in Pharmacy
Purchasing and Products, only 31% of respondents indicated
their facilities were in full compliance with standards that will
become effective in November of 20236. An even more alarming
statistic is that only 76% of respondents indicated their facilities
were in full compliance with the 2008 version of USP <797>6.
DISCUSSION
The compounded sterile preparation goals of ISMP and
USP are both rooted in ensuring that safe medications are
available to patients when they are needed, ISMP with the
Guidelines for Sterile Compounding and the Safe Use of Sterile
Compounding Technology, and USP with General Chapter <797>.
Although, in some ways, the two organizations approach the
goals differently, there is overlap in that they both focus on
processes to achieve the goals. It’s this process overlap that
can allow IVWFM systems with broad functionality such as the
DoseEdge system to support the needs of pharmacies in their
pursuit of compliance with both organizations’ guidelines.
From an ISMP perspective, the use of technology such as an
IVWFM system to improve the safety, efficiency, and prioritization
of compounding within the cleanroom is a well-known and frequent
topic of discussion. In fact, ISMP includes this in their 2022-2023
Targeted Medication Safety Best Practices for Hospitals and has
done so since 20167. These improvements can be achieved by
automating potentially error-prone processes that have traditionally
been performed manually. These error-prone processes can
include researching and following the correct and complete
compounding process, manually performing dose calculations
and determining appropriate BUDs, prioritizing urgently needed
products and using the ‘syringe pull-back’ or ‘proxy’ method for
indicating volumes of drugs injected into final containers.
Additionally, in 2022, “ISMP Guidelines for Sterile Compounding
and the Safe Use of Sterile Compounding Technology”
was published. It contains essential technology attributes,
safe pharmacy processes, safety gaps, and associated
best practices for various technologies such as automated
compounding systems, IV robotics and IVWFM systems.
The ISMP essential attributes for IVWFM systems are
listed below. Many align nicely to address the gaps
or issues associated with CSP preparation8.
ISMP Essential Technology Attributes
DoseEdge
System
Functionality
IV workflow management systems are interfaced
with the electronic health record to eliminate order
transcription from one system into another.
If a compounded sterile preparation has been
discontinued before initiation of the compounding
process, the system interface allows for the
removal of these products from the queue.
IV workflow management systems allow users
to create a master formulation record for non-
patient specific batch, stock solution, and patient-
specific compounded sterile preparations.
When master formulation records are
created, the IV workflow management system
prompts for an independent double check,
which is documented in the system.
Master formulation record changes are
timestamped, saved, and identify the
user who made the modification.
IV workflow management systems
provide an electronic log of changes
made to the database by users.
IV workflow management systems allow users to
customize the incoming order queue to prioritize work.
Machine-readable coding (e.g., barcode, RFID)
is used to verify source products, including
diluents, during the compounding process.
IV workflow management systems automatically
perform calculations or conversions.
IV workflow management systems guide users
through essential steps in the compounding
process including which steps require video
or still images or gravimetric analysis.
Image-capture pictures are clear such that syringe
graduation marks, drug and/or diluent names, lot
numbers, and expiration dates are easily visible.
CASE STUDY
www.baxter.com
IV workflow management systems that use
gravimetric analysis prevent users from creating
master formulation records for preparations
that are outside the system’s tolerance limits,
and if staff attempt to weigh a volume outside
the integrated scale’s tolerance limit the IV
workflow management system alerts the user.
IV workflow management systems document
all steps and components of the compounding
process (e.g., products used, the practitioner
who performed the compounding, the primary
engineering control, machine readable code scans,
date and time of preparation, alerts or warnings
presented during the process, the practitioner
who verified the preparation), and the information
is available to users in a log and/or report.
IV workflow management systems allow for
remote verification using video or image capture,
and, when used, gravimetric analysis.
IV workflow management systems track beyond-use
dating of opened or reconstituted products to warn
practitioners and prevent use of an expired product.
IV workflow management systems allow
for customization of labels (e.g., tall man
lettering, color print, reverse print, electronic
health record compatible barcode).
IV workflow management systems limit
the printing of the dispensing label until the
compounding process is complete.
Workload (e.g., incoming load) is documented
by the technology and captured in a report to
inform and facilitate operational improvement.
Close-call compounding events (e.g., wrong
drug scans) intercepted by the technology are
captured in a report to facilitate compounding
error analysis and process improvement.
Data in vendor reports are provided in a
useful format and do not require significant
manipulation by the end user.
When a system update is available, IV
workflow management system vendors
ensure all customers receive and install the
update in a reasonable timeframe.
2022 ISwMP Guidelines for Sterile Compounding and the Safe Use of Sterile Compounding Technology
A - Can be obtained from DoseEdge Technical Support
The use of IVWFM systems to help meet the Chapter <797>
standards is discussed far less, if at all. However, given the
broad functionality of some of these systems, such as the
DoseEdge system, they can influence pharmacy procedures and
documentation practices etc. which can directly or indirectly support
these requirements.
The following are many of the standards from the 2023 version of
USP <797> that could potentially be supported by using IVWFM
systems5.
USP Chapter <797> Standards
How DoseEdge
Functionality Could
Provide Support
3. PERSONAL HYGIENE AND GARBING
Personal hygiene and garbing are
essential to maintain microbial control of
the environment. Most microorganisms
detected in cleanrooms are transferred
from individuals. Squamous cells are
normally shed from the human body
at a rate of 106 or more per hour, and
those skin particles are covered with
microorganisms. Individuals entering a
compounding area must be properly garbed
and must maintain proper personal hygiene
to minimize the risk of contamination
to the environment and/or CSPs.
Individuals that may have a higher risk of
contaminating the CSP and the environment
(e.g., personnel with rashes, recent tattoos,
oozing sores, conjunctivitis, or active
respiratory infections) must report these
conditions to the designated person(s).
The designated person(s) is responsible for
evaluating whether these individuals should
be excluded from working in compounding
areas before their conditions have resolved
because of the risk of contaminating
the CSPs and the environment.
Remote verification
could help decrease
the number of
pharmacists required
to enter the cleanroom
to verify doses
including in-process
and final checks.
This can be especially
beneficial on off-shifts
when staffing may
be lower or when
pharmacist verifiers
with higher risks
for contamination
may be the only
pharmacist on duty.
4. FACILITIES AND
ENGINEERING CONTROLS
The design of the facility should
take into account the number of
personnel and their movements.
4.1 Protection from Airborne Contaminants
Proper design and controls are required
to minimize the risk of exposure of
CSPs to airborne contaminants.
Total airborne particle counts by ISO
classification must not be exceeded:
ISO 5 = 3520 particles/m3
ISO 7 = 352,000 particles/m3
Remote verification
can help minimize
the number of
pharmacist verifiers
needing to enter the
cleanroom which
may be able to affect
the overall design.
This decrease in
staff needing to enter
the cleanroom can
also be used as a
control mechanism
to decrease airborne
contaminants.
CASE STUDY
www.baxter.com
6. MICROBIOLOGICAL AIR AND
SURFACE MONITORING
6.2.3 Viable air sampling data
evaluation and action levels
Viable airborne particle counts
by ISO classification must not
exceed actionable levels:
ISO 5 > 1 cfu/m3
ISO 7 > 10 cfu/m3
6.3.3 Surface sampling data
evaluation and action levels:
ISO 5 > 1 cfu/media device
ISO 7 > 10 cfu/media device
The decrease in
staff needing to
enter the cleanroom
associated with
remote verification
can also be used as
a control mechanism
to decrease viable
air and surface
contaminants.
11. MASTER FORMULATION AND
COMPOUNDING RECORDS
11.1 Creating Master Formulation
Records (MFR)
An MFR is a detailed record of procedures
that describes how the CSP is to be
prepared. An MFR must be created for all
CSPs prepared from nonsterile ingredient(s)
or CSPs prepared for more than one patient.
11.2 Creating Compounding Records (CR)
CR documents the compounding of
each CSP. A CR must be created for all
Category 1, Category 2, and Category
3 CSPs. A CR must also be created for
immediate-use CSPs prepared for more
than one patient. The CR must be created
to document the compounding process.
A prescription or medication order or
label may serve as the CR. If an ACD,
workflow management system, or other
similar equipment is used, the required
information in the CR may be stored
electronically as long as it is retrievable
and retains the required information.
The following
DoseEdge
functionality can be
used in aggregate to
support most/all the
requirements for the
contents of an MFR
and CR, and help
ensure that the MFRs
and CRs are followed:
• Customizable
Drug Formulary
• Customizable
Product Formulary
• Customizable
Actions
• Customizable
Procedures
• Customizable
Scan Events
• Storage
capabilities
• Customizable
product-specific
information fields
12. RELEASE INSPECTIONS AND TESTING
12.2 Sterility Testing
For Category 2 CSPs assigned a BUD
that requires sterility testing (see
Table 13) and all Category 3 CSPs,
the testing must be performed.
12.3 Bacterial Endotoxins Testing
Category 2 injectable CSPs compounded
from one or more nonsterile component(s)
and assigned a BUD that requires
sterility testing and Category 3 injectable
CSPs compounded from one or more
nonsterile component(s) must be tested
to ensure that they do not contain
excessive bacterial endotoxins.
Customizable Actions
and/or Procedures
can be used to
remind compounders
when sterility and/or
bacterial endotoxin
testing (or other
requirements) needs
to be completed.
14. ESTABLISHING BEYOND-USE DATES
Each CSP label must state the date, or
the hour and date, beyond which the
preparation must not be used and must
be discarded (i.e., the BUD). The BUD is
determined from the date and time that
preparation of the CSP is initiated.
14.2 Parameters to Consider
in Establishing a BUD
When establishing a BUD for a
CSP, compounders must consider
parameters that may affect quality.
The BUDs for CSPs are based primarily
on factors that affect the achievement
and maintenance of sterility, which
include, but are not limited to:
• Conditions of the environment
in which the CSP is prepared
• Aseptic processing and
sterilization method
• Starting components (e.g., sterile
or nonsterile ingredients)
• Whether or not sterility
testing is performed
• Storage conditions (e.g.,
packaging and temperature)
14.3 Establishing a BUD for a CSP
The BUD must not exceed the
shortest remaining expiration
date of any of the commercially
available starting components.
14.5 Multiple-Dose Containers
The use of preservatives must be
appropriate for the CSP formulation
and the route of administration. For
example, the preservative must not be
inactivated by any ingredients in the
CSP, and some preservatives are not
always appropriate for the patient (e.g.,
neonates) or route of administration (e.g.,
intrathecal or ophthalmic injection).
After a multiple-dose CSP container
is initially entered or punctured, the
multiple-dose container must not be
used for longer than the assigned BUD
or 28 days if supported by antimicrobial
effectiveness testing results on
the CSP, whichever is shorter.
BUDs are
automatically
calculated from the
time the compounding
process is initiated.
They can be
customized and
automated to
account for the many
options that are
available between
and within the three
Compounding
Categories
BUDs can be
customized at the
dose level based on:
• Starting
components
used in the dose
• Location of
preparation
(environmental
conditions such
ISO classified
vs SCA/RABS)
• Storage conditions
• Processes used
during preparation
(including
sterility testing)
The BUD of individual
doses are compared
to the BUDs or
expiration dates of the
components used in
dose to ensure they
are appropriate.
With ‘Preservative-
free” and “Route
of Administration”
designations in the
Product Formulary,
inappropriate
component use
can be prevented.
“Work in Progress”
products and labels
can automate BUDs
for components used
during preparation
CASE STUDY
www.baxter.com
15. USE OF CONVENTIONALLY
MANUFACTURED PRODUCTS
AS COMPONENTS
15.1 Use of Conventionally Manufactured
Single-Dose Containers
A conventionally manufactured single-dose
container is a container closure system
that holds a sterile product for parenteral
administration (injection or infusion) that
is not required to meet the antimicrobial
effectiveness testing requirements. If a
single-dose vial is entered or punctured only
in an ISO Class 5 or cleaner air, it may be
used up to 12 h after initial entry or puncture
as long as the labeled storage requirements
during that 12-h period are maintained.
Opened single-dose ampules must
not be stored for any time period.
15.3 Use of Conventionally Manufactured
Pharmacy Bulk Packages
A conventionally manufactured pharmacy
bulk package is a container of a sterile
product for parenteral use that contains
many single doses. The contents are
intended for use in a pharmacy admixture
program and are restricted to the sterile
preparation of admixtures for infusion
or, through a sterile transfer device, for
the filling of empty sterile containers.
The pharmacy bulk package must be
used according to the manufacturer’s
labeling (see <659>, General Definitions,
Injection Packaging Systems). The
pharmacy bulk package must be entered
or punctured only in an ISO Class 5 PEC.
“Work in Progress”
products and labels
can also automate
BUDs for single dose
products, multiple
dose products and
pharmacy bulk
packages used
during preparation
18. QUALITY ASSURANCE AND QUALITY
CONTROL
18.1 Notification About and Recall of Out-of-
Specification Dispensed CSPs
If a CSP is dispensed or administered before
the results of release testing are known, the
facility must have procedures in place to:
• Immediately notify the prescriber of
a failure of specifications with the
potential to cause patient harm (e.g.,
sterility, strength, purity, bacterial
endotoxin, or other quality attributes)
• Recall any unused dispensed
CSPs and quarantine any stock
remaining in the pharmacy.
• Determine the distribution of any
affected CSP, including the date
and quantity of distribution.
• Identify patients who have
received the CSP.
Lot number tracking
can be used to
trace products
and components
to individual
patient doses.
CONCLUSION
The safety, efficiency, and waste-reduction benefits with the use
of IVWFM systems are well-established. ISMP has put forth much
effort in defining what an effective system should be capable of and
recommending their use among other technologies in the cleanroom.
Although IVWFM systems are only used in a minority
of facilities, that number continues to grow due to an
ever-increasing focus on safety and efficiency.
With the updated version of USP <797> effective on November
1, 2023, there is also a heightened interest in what facilities
need to do to become compliant before the effective date.
IVWFM systems with broad functionality such as the
DoseEdge system, can help support pharmacies in their
pursuit of regulatory compliance, optimized workflows,
compounding efficiency, and most of all, patient safety.
The DoseEdge System is not intended to replace the knowledge,
judgment or expertise of pharmacists and pharmacy technicians
in the preparation of IV admixtures or oral doses.
For safe and proper use of the product mentioned herein,
please refer to the appropriate Operator's Manual.
References
1. Stephen F Eckel, et al. Multicenter study to evaluate the benefits of technology-assisted workflow
on i.v. room efficiency, costs, and safety, American Journal of Health-System Pharmacy, Volume 76,
Issue 12, 15 June 2019, Pages 895–901.
2. Elizabeth Flynn, et al. Observational study of accuracy in compounding i.v. admixtures at five
hospitals, American Journal of Health-System Pharmacy, Volume 54, 15 April 1997, Pages 904-12.
3. ISMP Medication Safety Alert Newsletter October 22, 2020 Volume 25, Issue 21. Pg 1-5
4. Pharmaceutical compounding—sterile preparations (general information chapter 797). In: The
United States Pharmacopeia, 35th rev., and the National Formulary, 30 ed. Rockville, MD: The United
States Pharmacopeial Convention; 2012: pp 2-38 State of Pharmacy Compounding.
5. Pharmaceutical compounding—sterile preparations (general information chapter 797). In: The
United States Pharmacopeia, https://online.uspnf.com/uspnf/document/1_GUID-A4CAAA8B-6F02-
4AB8-8628-09E102CBD703_7_en-US35th rev.pp 1-33
6. Pharmacy Purchasing and Products, 2023; 4:1-53 National Survey (Can’t get fill reference info)
7. ISMP Targeted Medication Safety Best Practices for Hospitals, 2022-2023
8. 2022 ISMP Guidelines for Sterile Compounding and the Safe Use of Sterile Compounding
Technology
Baxter and DoseEdge are trademarks of Baxter International Inc.
US-MD14-230014 v1.0 10/2023
Chuck Ferris, R.Ph.
Associate Director, Medical Affairs
~ Baxter Healthcare Corporation
Jeff Brittain, PharmD, BCPS
Senior Manager, Medical Affairs
~ Baxter Healthcare Corporation
Medication errors
can occur at any
point in the infusion
therapy process.
Help protect
patients, from
dose preparation
to administration.
Only Baxter can help you create
a full spectrum of IV medication
protection, safeguarding every step
from pharmacy to bedside.
DoseEdge.com
SpectrumIQ.com
Rx Only. For safe and proper use of the product mentioned herein, please refer to the appropriate
Operator’s Manual or Instructions for Use.
and to help reduce opportunities for error. It is not intended to replace the knowledge, judgment,
or expertise of pharmacists and pharmacy technicians in the preparation of IV admixtures or
oral doses.
Baxter, DoseEdge and Spectrum IQ are registered trademarks of Baxter International Inc.
or its subsidiaries.
US-MD44-210018 v1.0 04/2021
SpectrumIQ
INFUSION SYSTEM