Roche_IHCCompWhitePaperITALY_FOR CLIENT REVIEW-4

White paper
Optimizing IHC workflow in anatomic pathology with the
VENTANA BenchMark ULTRA IHC/ISH staining system

2016 Italian Laboratory Study



Laboratory fast facts Workflow advantages with automation in IHC
• Large general hospital in Italy (1,850 staining
beds)
• Teaching hospital for the local medical Workflow benefits provided by automating the immunohistochemistry (IHC) staining process
school vary by staining platform. Choices available in the market today range from a platform that
• IHC slide volume: 45,757 slides in 2015 supports both individual slide staining and batching (the VENTANA BenchMark ULTRA
IHC/ISH staining platform), to instruments that require mini-batching or full batching
Advanced staining instrumentation to achieve full instrument utilization. Because batch processes have traditionally been a
• The BenchMark ULTRA IHC/ISH staining reality for IHC staining in many anatomic pathology laboratories (regardless of the type of
system (4) instrumentation used), it can be challenging for laboratory personnel to understand the
• Dako Omnis (2) workflow benefits of using a platform designed to support single piece flow.

Study materials and methods Hypothesizing that the BenchMark ULTRA system, even when used as a full batching
At the time of data collection for this instrument, would deliver greater workflow gains than mini-batching with Dako Omnis,
study: analysts from Roche Diagnostics studied IHC workflow inside an AP laboratory located
• Technicians ran the BenchMark ULTRA in Italy in 2016. For IHC staining in everyday operations, the laboratory uses both the
system as a full-batch instrument, BenchMark ULTRA IHC/ISH system and Dako Omnis, allowing a side-by-side comparison of
sorting and loading runs of 30 slides at workflow between the two instruments.
once (full instrument capacity).
• On Dako Omnis, technicians batched in Through objective data collection, Roche analysts captured the differences in workflow and
drawers of five slides in accordance with time spent on manual steps in IHC staining, and found their hypothesis to be substantiated.
the instrument’s design. The run As demonstrated by the results of this study and similar studies, the BenchMark ULTRA
observed for Dako Omnis included 45 system, even when used as a batch staining instrument, provides workflow gains and time
slides (nine trays of five slides each, savings over Dako Omnis. This white paper explores those research findings in more detail.
loaded into the instrument three trays at
once).* Additionally, because the BenchMark ULTRA system provides individual slide staining
capabilities with continuous access, Roche analysts concluded that the laboratory in
* The findings of this study are based on a fully Italy has the opportunity to further optimize efficiency by replacing batch IHC staining
operational Dako Omnis instrument in which instruments and processes with the BenchMark ULTRA system and single piece flow. As
technicians fully loaded each tray (5 slides). The seen in other comparative analysis studies, single piece flow processes used in conjunction
data was collected from one Omnis and one with the BenchMark ULTRA system deliver optimal efficiency gains.1
BenchMark ULTRA for the duration of the study.

Pictured here are the laboratory’s two Dako Omnis instruments (front and center) and one of the
laboratory’s four BenchMark ULTRA instruments (right background). Only the center instrument was
available to the researchers during the course of this study.

1 See “Maximizing IHC/ISH capacity and throughput with continuous access and single piece flow”
(2016 Australian laboratories study) and “Maximizing capacity and throughput with continuous flow”
(2014 United States laboratories study).

Efficient slide management: Faster availability of
completed slides

During the course of this study, Roche analysts tracked and documented how much time
passed before the first 30 slides became available on each instrument. The result was
a difference of 41 minutes: the first 30 slides on the BenchMark ULTRA system became
available after two hours and 46 minutes, while on Dako Omnis, the first 30 slides took three
hours and 27 minutes (see Figure 1).

Individual slide staining drawers improve slide availability

First slide 2h21
available 2h40

First 5 slides 2h37 BenchMark ULTRA
available 2h40 Dako Omnis

First 30 slides 2h46
available 3h27

STAT slide 2h21
available
4h00

Minutes 0 50 100 150 200 250

Figure 1: The individual slide staining drawers of the BenchMark ULTRA system enable completed slides
to become available faster than the “drawers of five” on the Dako Omnis instrument.

Much of that additional time on Dako Omnis came from a bottleneck that occurred in slides
16-30, due to the Dako Omnis only having enough capacity in the pre-treatment module
to accommodate a maximum of three trays (with up to five slides per tray) at any one time.
At five slides per tray, slides 1-15 went through pre-treatment first, forcing slides 16-30
into a non-value added wait point in which processing could not continue until slides 1-15
completed the pre-treatment modules. Even with full batching, this bottleneck was avoided
when using the BenchMark ULTRA system because all slides were placed in individual
drawers, thereby eliminating the batching requirements. As a result, the amount of time it
took for slides 1-30 to become available was significantly reduced.

Similarly, researchers noted that the first slide became available on the BenchMark ULTRA
system 19 minutes sooner than the first slide on Dako Omnis. While that time difference may
be explained in part by variations in staining protocols, it also represents an inherent benefit
of the individual slide staining drawers and continuous access design of the BenchMark
ULTRA system: when a slide was complete, it became immediately available for removal
without disrupting any in-process slides. By contrast, with the five-slide rack design of Dako
Omnis, technicians could not access the first slide completed until every additional slide in
the first drawer became available.

Optimized management of high priority slides

Due to its inability to process one slide independently of all other slides without drastically
reducing instrument capacity utilization, managing high priority slides (also known as urgent
or STAT slides) is much more challenging with Dako Omnis. The instrument design only
provides the opportunity to prioritize the flow of a high priority slide if the rack containing the
slide is loaded before the other racks. Therefore, managing urgent requests on Dako Omnis
essentially translates to a process whereby the first slide or tray loaded onto the instrument
will be the first slide or tray to come off; the system has no capability to prioritize.

During data collection for this study, one urgent request was processed on Dako Omnis.
Because it could not be prioritized, four hours passed before the processed STAT slide
became available.

Because the lab batched only routine requests for staining on the BenchMark ULTRA system,
no STAT slides were processed on the BenchMark ULTRA system during the course of this
study. However, the instrument’s individual slide drawers and continuous access capabilities
allowed a comparison to be made between the four-hour STAT turnaround on Dako Omnis
and the two hour and 21 minute turnaround for the first available slide on the BenchMark
ULTRA system – a difference of one hour and 39 minutes.

It is worth noting that if the laboratory were to adopt single piece flow, the difference in STAT
availability would be even greater. In a single piece flow environment using the BenchMark
ULTRA system, all slides including STAT requests become available immediately after
processing is complete. Furthermore, regardless of workflow (batching or single piece flow),
the individual slide staining drawers of the BenchMark ULTRA system bring every laboratory
the opportunity to access one or more drawers for urgent requests with minimal effect on
overall throughput and instrument utilization. With one drawer not in use except on STAT
orders, 29 other slides can run at all times with full continuous access capabilities.

By contrast, with the batch-only drawer design of Dako Omnis (five slides per drawer for
full utilization), the impact of holding a drawer for urgent requests would be five times
greater. In terms of instrument utilization versus capacity, a single slide represents 100%
drawer utilization on the BenchMark ULTRA system, compared to 20% drawer utilization on
Dako Omnis.

With the BenchMark ULTRA system, continuous access to 30 individual slide drawers allows labs to
reserve a drawer for urgent requests with minimal effect on overall productivity. Even with one drawer
not in use except on high priority orders, 29 other slides can run at all times with full continuous access
capabilities.

Reduced time spent on manual tasks

Roche analysts tracked and documented the amount of time technicians spent on manual
activities associated with the preparation of instrument startup and operations for IHC
staining (one run per instrument). They found the total technician time spent on these types
of manual activities decreased by 44 minutes with the BenchMark ULTRA system. Figures 2
and 3 delineate the activities and time spent on each instrument, while Figure 4 provides an
at-a-glance illustration of the differences in total duration of manual activities per run per
instrument.

Dako Omnis Platform (one run, n=45 slides) The BenchMark ULTRA system (one run, n=30 slides)

Technical time Activity type Technical time Activity type
in minutes in minutes
Manual Manual
Activities in preparation for instrument startup Manual Activities in preparation for instrument startup Manual
Manual Manual
1 Empty NH2 tank 0.90 Manual 1 Load 35 ready-to-use reagents 1.95 Automatic
2 Empty NH3 tank 0.83 Manual 2 Substitute one reagent 0.63 3 of 4 steps
3 Empty NH4 tank 0.86 Manual 3 Refill reaction buffer tank 0.72 performed
4 Empty HZ tank 3.83 Manual 4 Cleaning run 11.92 manually
5 Refill water (two tanks) 1.67
6 Replace five strips 2.17 Manual Subtotal of time spent 3.30 minutes*
7 Refill buffer solution (including 2.87 Manual
cleaning the tank) 9 of 9 steps on manual activities:
8 Refill reagents 2.83 performed
9 Refill antibodies 0.98 manually

Operations for IHC staining

Subtotal of time spent 16.94 minutes 1 Sort slides by designated 7.22 Manual

on manual activities: instrument Manual
Manual
2 Sort slides based on antibodies 0.91 Manual
Manual
3 Label slides 6.65 Manual
Manual
Operations for IHC staining 4 Load slides in single-slide drawers 1.13
Manual
5 Start run 0.08 Manual
Automatic
1 Sort slides by designated 7.22 Manual 6 Unload slides 1.00

instrument 7 Position slides in rack for 1.00

2 Label slides 11.25 Manual dehydration

3 Pre-sort slides for rack filling 2.25 Manual 8 Cleaning slides 1.68

(based on high and low PH) 9 Dehydration with alcohol 24.00

4 FIll racks with slides 4.50 Manual 10 Coverslipping 12.00

5 Load racks in instrument 2.70 Manual Subtotal of time spent 43.67 minutes* 9 of 10 steps

6 Start run 0.75 Manual on manual activities: performed

7 Unload racks 3.00 Manual manually

8 Unload slides from racks 4.33 Manual Total time spent on 46.97 minutes* 12 of 14 steps

9 Position slides in racks for 1.50 Manual manual activities performed

dehydration per run manually

10 Dry racks on table and organize 0.75 Manual

them Figure 3: Technician time spent on manual activities in preparation of
instrument startup and operations for IHC staining of 30 slides on the
11 Dehydration with alcohol 36.00 Manual BenchMark ULTRA system.

12 Coverslipping 18.00 Automatic

Subtotal of time spent 74.25 minutes* 11 of 12 steps
performed
on manual activities: manually
20 of 21 steps
performed
manually
Total time spent on manual 91.2 minutes*

activities per run



Figure 2: Technician time spent on manual activities in preparation of
instrument startup and operations for IHC staining of 45 slides on Dako
Omnis.

* Totals represent time spent on manual activity only (excludes duration of automated activity).

It is relevant that the calculations shown in figures 2 and 3 are based on 45 slides for Dako
Omnis and 30 slides for the BenchMark ULTRA system. However, taking into consideration all
steps needed for both the instruments, a calculated ratio of “manual time needed per slide”
revealed that technicians spent 23% more time on manual tasks associated with preparation
and operations with Dako Omnis. For such activities, technicians spent two minutes and one
second per slide on Dako Omnis, compared to one minute and 34 seconds per slide on the
BenchMark ULTRA system.

Time spent on manual pre- and post-staining activities

Preparation of 3 min, 18 sec
instrument 16 min, 56 sec
startup

Operations for 43 min, 40 sec
IHC staining
Total time 74 min, 15 sec
spent on
manual 46 min, 58 sec
activities
91 min, 12 sec

Minutes 0 10 20 30 40 50 60 70 80 90

BenchMark ULTRA Dako Omnis
(n=30 slides) (n=45 slides)

Figure 4: Technician time spent on manual activities in preparation of instrument startup and operations
for IHC staining on the BenchMark ULTRA system (n=30 slides) compared to Dako Omnis (n=45 slides).

Less instrument maintenance required

In terms of instrument maintenance and its impact on laboratory workflow and productivity,
the findings of this study show the BenchMark ULTRA system offers the advantage. With
the laboratory’s assistance, researchers captured data that enabled a comparison of time
required per year for the maintenance of one Benchmark ULTRA system versus one Dako
Omnis. Figure 5 illustrates the difference in maintenance hours per year, based on two runs
per day per instrument.

Time spent per year on instrument maintenance

Manual 43.3
maintenance 230.9

Automated 112.9 BenchMark ULTRA
maintenance 95.7 Dako Omnis

Total maintenance 156.2
(automated and
326.6
manual combined)

Hours per year 0 100 200 300 400

Figure 5: Comparison of time required per year for maintenance for one BenchMark ULTRA system
versus one Dako Omnis. Analysis based on two runs per day at approximately 23,000 IHC slides per year.

As demonstrated in Figure 5, the BenchMark ULTRA system saved the laboratory more
than 187 hours per year in manual activities associated with instrument maintenance.
When calculated across 260 working days per year, that time savings equates to 43 minutes
per day. After subtracting the additional 17.2 hours dedicated to automated instrument
maintenance on the BenchMark ULTRA system, researchers determined the total net time
savings for instrument maintenance (both automated and manual) equates to approximately
170 hours per year. With less time spent on manual tasks comes the potential to increase
slide volume without the need for additional staff, or to reallocate that time for more value-
added technician activities that can make a positive impact on quality of service.

Additionally, researchers noted that sorting slides to accommodate two types of IHC staining
instruments costs the laboratory 26 hours each year in non-value added activity. That figure
illustrates the inefficiency of sorting slides in general, underscoring the much larger gains
that can be achieved by eliminating batching and sorting from the laboratory entirely – lean
workflow optimization that only the BenchMark ULTRA system is designed to support.

Recognized benefits of single piece flow Conclusion

• Supports chain of custody integrity The results of this analysis demonstrate that the BenchMark ULTRA IHC/ISH system, the
only IHC staining platform designed to support single piece flow, outperforms mini-batching
• Reduces risk of misidentification errors instruments regardless of the workflow environment. Even when used as a full-batch
instrument, loaded and started for 30 slides at once compared to mini-batches on the Dako
• Enables optimal instrument utilization Omnis, the BenchMark ULTRA system delivered substantial time savings in:
throughout each work day, when
combined with continuous access • Total time until first 30 slides become available (41 minutes faster)
technology • Manual tasks associated with preparing for instrument start up and the operations of IHC
staining (44 fewer minutes per run)
• Increases efficiency by eliminating batch • Routine maintenance tasks (43 minutes saved per day)
sorting
Opportunities to further optimize workflow, instrument utilization and turnaround time by
Benefits of continuous access combining the BenchMark ULTRA system with single piece flow have been documented in
similar comparative studies in other parts of the world. For example, in a 2016 workflow study
Continuous access made possible with of laboratories in Australia, average instrument utilization was shown to increase by 28%
individual slide staining drawers brings where the BenchMark ULTRA system was combined with single piece flow, and same-day
many benefits compared to batch turnaround increased by an average of 12%.1 A 2014 study of laboratories in the United
processing: States showed continuous access instrumentation enabled throughput increases as high as
91% when compared to batching.2 Similar advantages are available to laboratories in Europe
• Allows 30 slides with up to 30 different that adopt continuous access instrumentation and single piece workflow.
protocols to run simultaneously

- Eliminates the need to batch and sort

- Supports proven benefits of single
piece flow in lab operations

• Accommodates urgent and late arriving
samples without requiring suboptimal
instrument utilization

• Enables continuous runs at maximum
instrument capacity by allowing
technicians to remove and replace
individual slides as soon as they are
complete

• Runs ISH samples alongside IHC by
providing the ability to change out IHC
slides while simultaneously continuing
the longer-running ISH stains

• Empowers labs to optimize daily
throughput and, if desired, reserve
capacity for future workload increases

1 “Maximizing IHC/ISH capacity and throughput with continuous access and single piece flow” (2016
Australian laboratories study).

2 “Maximizing capacity and throughput with continuous flow” (2014 United States laboratories study).



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