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Innovation in Immunohistochemistry (IHC) Staining: Single Piece Flow IHC Slide Processing Authors: Erika Klohe, BS, MBA, Claudiu V. Cotta, MD, PhD, Amy Posch, Renata Klinkosz, Elizabeth Rowe, Ellen Magcamit-Labay, Fredericka Jones, Michelle Wayman, Derick Mangalindan, Stephanie Sanchez, Kathleen Sergott, Sherri Lomayesva, Clinton Yip, Jeff Pearson, Mark Torowus, James Walker, Heather Free Editor: Mark Terry DARK Daily Laboratory and Pathology News @ darkdaily.com
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Innovation in Immunohistochemistry (IHC) Staining: Single Piece Flow IHC Slide Processing

Authors: Erika Klohe, BS, MBA, Claudiu V. Cotta, MD, PhD, Amy Posch, Renata Klinkosz, Elizabeth Rowe, Ellen Magcamit-Labay, Fredericka Jones, Michelle Wayman, Derick Mangalindan, Stephanie Sanchez, Kathleen Sergott, Sherri Lomayesva, Clinton Yip, Jeff Pearson, Mark Torowus, James Walker, Heather Free

Editor: Mark Terry

DARK Daily Laboratory and Pathology News @ darkdaily.com

www.darkdaily.com ©2011 Dark Intelligence Group, Inc.

Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 2

Table of Contents

Executive Summary� 3

Preface:Immunohistochemistry(IHC)andIHCWorkflow 6

Introduction 9

Chapter 1:SinglePieceFlowIHCPlatforms 11

Chapter 2:CCFIHCWorkCell 12

Chapter 3:CaseStudy 14

Chapter 4:Results:TimefromPathologistOrderedIHCStaintoInstrumentVerification 17

Chapter 5:Results:TimefromLISOrdertoRunCompletion 19

Chapter 6:Results:ImprovedProductivityintheIHCWorkCell 21

Conclusions 22

References 23

AppendicesA-1AbouttheAuthors 25A-2AboutVentaMedicalSystems,Inc./Roche 26A-3AboutDARKDaily 27A-4AboutTheDarkIntelligenceGroup,Inc.,andTHEDARKREPORT 28A-5AbouttheExecutiveWarCollegeonLaboratoryandPathologyManagement 29A-6 About MarkTerry 31Terms of Use 36

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 3

©2011 Dark Intelligence Group, Inc.

Executive Summary�Not all laboratory tests and procedures are easy to automate. In

particular, complex laboratory workflows that utilize microscopy or

imaging can be difficult to fully automate. In recent years a number

of approaches have been devised to automate part of the laboratory

workflow for staining processes, imaging procedures, or to link

various automated subunits of the workflows. Immunohistochemistry

(IHC) is a good example of the difficulties of creating a fully

automated workflow. It is estimated that 70% of the workflow in a

histology laboratory is manual. Key areas of automation are typically

staining and imaging. Most automation in the staining area depends

upon robotic pipetting systems, sometimes linked with ancillary

delivery systems for wash buffers and other bulk fluids.

Automated staining typically relies on batch staining, i.e., staining

large numbers of slides simultaneously. With an emphasis on

efficiency, especially using Six Sigma and Lean philosophies,

laboratories are attempting to find more effective and flexible ways to

handle automated staining in the immunohistochemistry laboratory

that do not rely on batch staining, but utilize single piece flow

processing system.

The Cleveland Clinic Foundation (CCF) in partnership with Ventana

Medical Systems, Inc., modified their batch IHC work cell by

implementing the BenchMark ULTRA single piece flow staining

platform. They replaced the BenchMark instruments with four

VENTANA BenchMark ULTRA staining platforms, which created

a mix of batch (BenchMark XT instrument) and single piece flow

(BenchMark ULTRA staining platform) capabilities. This redefined

how they manage their slide handling techniques, optimizing slide

prioritization across single piece flow or batch systems when needed.

It is estimated

that 70% of

the workflow

in a histology

laboratory is

manual.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 4

©2011 Dark Intelligence Group, Inc.

It also removed delays associated with slide sorting and wait-times

related to the longest staining protocols. This resulted in STAT slides

being integrated more easily into routine workflow, and bulk reagents

and instrument output being maintained continuously throughout the

workday.

The Ventana workflow team conducted a detailed time analysis to

define the best method for implementing workflow improvements at

CCF. To reach the optimum CCF instrumentation mix and antibody

test menu, Ventana implemented and analyzed three different and

separate workflow states: “Batch Only,” “Batch and Single Piece Flow

without Workflow Consultation,” and “Batch, Single Piece Flow, with

Workflow Consultation.”

The Ventana workflow team measured the time intervals between three

data parameters in the IHC process: IHC order data from the LIS, slide

start data from the instrument, and slide completion reports derived

from staining platforms. Despite eliminating two instruments, slide

capacity remained unchanged. Reagent positions decreased, but there

was no impact on the number of slides processed.

In addition, the Ventana workflow team identified high-demand tests

so CCF could pre-load the most common reagents in their test menu

across the BenchMark ULTRA platforms. The new process allowed

CCF to more finely tune lower demand tests into three categories

of batch-runs: short IHC run time, long IHC run time, and in situ

hybridization (ISH). This workflow improvement shifted 77% of the

laboratory’s testing from batch processing to single piece flow staining

platforms (the four BenchMark ULTRAs) and moved CCF further than

expected toward Lean workflow.

The Ventana

workflow team

conducted a

detailed time

analysis to define

the best method

for implementing

workflow

improvements

at CCF.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 5

©2011 Dark Intelligence Group, Inc.

The study then analyzed results for a number of different parameters,

including:

• The time from LIS Ordered to Instrument Verification.

• The time from LIS Ordered to Run Completed.

• An evaluation of Improved Productivity in the IHC Work Cell.

CCF and Ventana concluded that optimizing the mix of IHC staining

platforms, along with incorporating Lean workflow processes,

resulted in significant improvement in test turnaround time, cut-

off times, and increased slide throughput per full-time employee.

In addition, workflow consultation and the incorporation of Lean

workflow philosophies improved efficiency in conjunction with those

found with the implementation of the BenchMark ULTRA single

piece staining platform.

Optimizing

the mix of

IHC staining

platforms,

along with

incorporating

Lean workflow

processes,

resulted in

significant

improvement in

test turnaround

time...

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 6

©2011 Dark Intelligence Group, Inc.

PrefaceImmunohistochemistry (IHC) and IHC Workflow

Laboratory tests and procedures that involve microscopy or imaging

tend to have very complex workflows that do not lend themselves

well to full automation. As Rene J. Buesa says in her 2009 article in

the Annals of Diagnostic Pathology, “After a few years of operation,

all histolabs develop workflow problems.” In recent years a number

of approaches have been devised to automate part of the laboratory

workflow for staining processes, imaging procedures, or to link

various automated subunits of the workflows.

Immunohistochemistry (IHC) is a good example of the difficulties

of creating a fully automated workflow. At its most basic, IHC

involves using biological reagents such as antibodies or probes to

identify specific proteins or genes on tissue specimens, which are

then visualized using several different types of imaging – such as

fluorescence or bright microscopy, for example. The complexity

that contributes to the challenges of full automation in IHC include

expansive diagnostic test menus, types and preparation of tissue, and

the staining preferences of individual pathologist.

IHC workflow begins with a surgical biopsy of a tumor. The

specimen is accessioned and examined, processed in paraffin blocks,

then prepared as tissue sections onto glass slides. Standard, routine

staining is typically H&E (hematoxylin and eosin), more slides are

prepared, collated and delivered, then provided to a histotechnologist

and/or pathologist to analyze. IHC is then ordered, the more

complicated IHC procedures are performed on the slides, which are

then collated and delivered to a histotechnologist and/or pathologist

to analyze. In many cases multiple images are digitized, which allows

the images to be analyzed side-by-side by the pathologist. A report is

created and the paraffin blocks and prepared slides are archived.

“After a

few years of

operation,

all histolabs

develop

workflow

problems.”

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 7

©2011 Dark Intelligence Group, Inc.

It is estimated that 70% of the workflow in a histology laboratory is

manual. Key areas of automation are typically staining and imaging

(which usually occurs between the Collate & Deliver and Read Slides

area). Generally, automated staining in IHC relies upon robotic

pipetting systems. In addition, some automated systems link wash

buffers and other fluids via ancillary delivery systems.

As a result, IHC instrument performance times depend upon

incubation times of individual reagents and on the amount of time it

takes for a robotic arm or arms to move from one slide station to the

next, or from reagent wells to slides. Therefore, throughput rate for

automated IHC instruments are calculated based on the total time

necessary for the instrument to perform a full staining run and on the

number of slides stained.

For the most part, IHC automation for staining procedures has used

“batch runs,” i.e., staining large collections of slides simultaneously.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 8

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This works reasonably well and provides good consistency and

quality of stain. However, modern laboratories have a continual push

for more efficiencies, often utilizing Six Sigma or Lean philosophies.

Lean essentially attempts higher levels of efficiency by optimizing

workflow. Batch processing of anything, however, does not fit in well

to the Lean philosophy.

In addition, an automated batch system does not adapt well to a STAT

sample that needs to be processed immediately. Some facilities and

companies have been working on developing more of a “single piece

flow processing” system, eliminating “batch processing” leading

to better run times and instrument capacity; it also provides more

flexibility in the workflow and better fits into Lean processes.

Modern

laboratories

have a continual

push for more

efficiencies...

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 9

©2011 Dark Intelligence Group, Inc.

IntroductionInnovation in immunohistochemistry (IHC) staining has evolved

significantly over the last two decades. The process of staining

has shifted from labor-intensive, manual techniques toward

semi-automated instruments with off-line processes such as

deparaffinization and antigen retrieval, and now to a new generation

of baking-through-staining automated instrumentation systems that

enable standardization, improved staining consistency, and expedited

turnaround times. While automation has positively influenced IHC

slide-staining quality and processes, the batch-run method has been

a constraint in achieving Lean workflow efficiencies and improved

productivity for the anatomic pathology laboratory.

In the article “Adapting lean to histology laboratories,” author Rene J.

Buesa discusses the evolution of IHC processes and the inherent “anti-

lean characteristics” of “large batch practice” that has permeated the

histolab culture in current times1.

This case study of the Cleveland Clinic Foundation (CCF) IHC

work cell analyzes the impact of implementing single piece flow

processing approach and comparing single piece flow output to batch

processing of IHC slides. Also, this paper examines how third-party

workflow consulting enhances the results associated with instrument

implementation by also incorporating Lean workflow concepts, such

as single piece flow.

The purpose of this study was to assess how Lean workflow concepts

can be incorporated with continuous flow instrumentation to improve

lab productivity and process. To analyze changes in workflow

efficiency, this study compares data from the following slide processing

milestones: LIS Ordered Time – the time that the test was ordered in the

The purpose of

this study was

to assess how

Lean workflow

concepts can be

incorporated

with single

piece flow

instrumentation

to improve lab

productivity and

process.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 10

©2011 Dark Intelligence Group, Inc.

LIS system; Instrument Verification Time – the time that the specimen

was placed on the instrument, as recognized by barcode reading; and

Run Complete Time – the time that the slide completed processing on

the instrument. These parameters were utilized to measure increases

in laboratory productivity and improvements to the flow of specimens

throughout the staining process.

These

parameters

were utilized

to measure

increases in

laboratory

productivity...

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 11

©2011 Dark Intelligence Group, Inc.

Chapter 1

Single Piece Flow IHC PlatformsIn October 2009, in collaboration with Ventana Medical Systems,

Inc., the Cleveland Clinic Foundation (CCF) modified their batch

IHC work cell by implementing the BenchMark ULTRA single

piece flow staining platform. Prior to this date, CCF used all batch

IHC automation, specifically a mix of VENTANA BenchMark and

BenchMark XT instruments.

The VENTANA BenchMark ULTRA staining platform is capable

of running 30 individual slides in a continuous and random access

format via independent slide processing drawers. Individual slide

processing eliminates the need to batch slides, maximizing run-time

efficiency and instrument capacity. It removes delays associated with

slide sorting and waiting for the longest staining protocol to finish

before gaining access to slides. The BenchMark ULTRA instrument

allows histotechnicians to load slides continuously as they are cut,

and unload completed slides as they finish staining. Accordingly,

STAT cases are easily absorbed into routine workflow and instrument

operators can replenish bulk reagents and manage instrument output

continuously throughout the workday while slides are processing.

It removes delays

associated with

slide sorting and

waiting for the

longest staining

protocol to finish

before gaining

access to slides.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 12

©2011 Dark Intelligence Group, Inc.

Chapter 2

CCF IHC Work CellCCF processes approximately 75,000 IHC slides per year, and staffs

the IHC lab five days per week from 6:30 a.m. to 3:00 a.m. Two

histotechnicians (HT) perform the tasks in the IHC work cell and

manage the various work streams in the lab. These work streams

include cutting IHC slides, IHC instrument operation (sample

labeling, loading/unloading slides and reagents, slide dehydration, and

cover slipping stained slides), preparing reagent and primary antibody

dilutions, performing manual stains, managing the Laboratory

Information System (LIS) interface, retrieving and filing blocks,

cutting control slides, and preparing slides for molecular testing. The

shifts overlap in the following manner:

• 6:30 a.m. – 4:00 p.m. 1 HT cutting slides,

1 HT operating IHC instruments

• 4:00 p.m. – 6:30 p.m. 1 HT cutting slides and

operating IHC instruments

• 6:30 p.m. – 8:30 p.m. 1 HT cutting slides,

1 HT operating IHC instruments

• 8:30 p.m. – 3:00 a.m. 1 HT cutting slides and

operating IHC instruments

Two

histotechnicians

perform the

tasks in the

IHC work

cell and

manage the

various

work streams

in the lab.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 13

©2011 Dark Intelligence Group, Inc.

IHC instrumentation used in the lab prior to October of 2009 was a

mix of BenchMark and BenchMark XT instruments. Table 1 shows

the number of slide and reagent positions the lab used to manage the

IHC caseload.

Table 1. Instrument Mix in the Lab (Prior to October 2009).

Instrument Type # of units Slide Positions Reagent Positions

BenchMark instrument 6 120 150

BenchMark XT instrument 4 120 140

Totals 10 240 290

Table 2 details the IHC cut-off time, batch run time, and slide

delivery time with 100% batch processing and instrumentation. Batch

processing represented the current state at the time of data collection.

Table 2. IHC Batch Order Cutoff and Run Times (Prior to October 2009).

IHC Order Cutoff Time

Average Batch Staining Start Time

Average Batch Run Completion Time

Slides Delivered to Pathologist

10:00 a.m. 11:00 a.m. 3:30 p.m. 4 p.m.

1:00 p.m. 2:00 p.m. 6:30 p.m. 8 p.m.

After 1:00 p.m. Overnight shift run Overnight 10:30 am (next day)

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 14

©2011 Dark Intelligence Group, Inc.

Chapter 3

Case Study�This case study analyzed the implementation of single piece flow

slide processing in the IHC work cell and measured gains in

workflow efficiency for slide processing and slide output. This study

also evaluated the benefits of incorporating workflow consulting to

balance CCF’s antibody test menu and instrumentation mix.

Workflow and Instrument Mix in the IHC Work Cell

Three separate workflow states were analyzed to measure the

productivity and efficiency in the IHC work cell. Table 3 shows the

IHC work cell time period, workflow state, and instrument mix.

Table 3. Cleveland Clinic IHC Work Cell States.

IHC Work Cell Time Period Workflow State Platform / Instrument Mix

A Until October 2009 Batch only 6 BenchMark instruments, 4 BenchMark XT instruments.

B October 2009 to January 2010

Batch and Single piece flow w/o Workflow Consultation

4 BenchMark XT instruments and 4 BenchMark ULTRA staining platforms in January 2010 soon after installation

C January 2010 to April 2010

Batch, Single piece flow, with Workflow Consultation

4 BenchMark XT instruments and 4 BenchMark ULTRA staining platform Lean workflow consultation measures implemented

Analysis of Workflow on Slide Processing

A workflow analysis was completed, measuring the time intervals

between three data parameters in the IHC process: IHC order

data from the LIS, slide start data from the instrument, and slide

completion reports derived from staining platforms. The following

This study

also evaluated

the benefits of

incorporating

workflow

consulting to

balance CCF’s

antibody test

menu and

instrumentation

mix.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 15

©2011 Dark Intelligence Group, Inc.

time intervals were compared across the three workflow states, as

detailed in Table 3 above:

• LIS Ordered to Instrument Verification (Pathologist Order to

Verified By Instrument)

• LIS Ordered to Run Completion (Pathologist Order to Slide Stain

Complete)

In October of 2009, the start of this study, the BenchMark instruments

were replaced with four VENTANA BenchMark ULTRA staining

platforms, thereby creating a mix of batch (BenchMark XT

instrument) and single piece flow (BenchMark ULTRA staining

platform) capabilities (see Table 4).

The resulting slide capacity for managing the annual IHC caseload

remained unchanged despite the elimination of two instruments.

Reagent positions decreased by ten in the new instrument

configuration; however, the decrease in reagent positions had no

impact on the number of slides that could be processed.

Table 4. Instrument Mix in the Lab (Post October 2009).

Instrument Type # of Units Slide Positions Reagent Positions

BenchMark ULTRA staining platform 4 120 140

BenchMark XT instrument 4 120 140

Totals 8 240 280

Benefits of Workflow Consultation and Lean

Workflow consultation identified high-demand tests based on volume,

and utilized this information to pre-load the most common reagents

in CCF’s menu across the BenchMark ULTRA platforms. Lower-

demand tests were batched on BenchMark XT instruments in the

following categories: short IHC run time, long IHC run time, and

in situ hybridization (ISH). The workflow plan ultimately shifted

The resulting

slide capacity

for managing

the annual

IHC caseload

remained

unchanged

despite the

elimination of

two instruments.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 16

©2011 Dark Intelligence Group, Inc.

77% of the lab’s testing from the batch processing systems to the

four BenchMark ULTRA single piece flow staining platforms. The

BenchMark XT instruments were used to run the remaining 23%

of the slide volume. Given the depth and breadth of CCF’s primary

antibody library, allocating the antibodies based on usage was a

critical step in establishing a Lean workflow.

Given the depth

and breadth of

CCF’s primary

antibody library,

allocating the

antibodies based

on usage was a

critical step in

establishing a

Lean workflow.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 17

©2011 Dark Intelligence Group, Inc.

Chapter 4

Results: Time from Pathologist Ordered IHC Stain to Instrument VerificationThe time from “LIS Ordered to Instrument Verification” and “LIS

Ordered to Run Completed” were compared across each of the three

workflow states detailed in Table 3. The analysis measured workflow

efficiencies in the IHC work cell, improved productivity in slide

processing, flow of specimens, and test turnaround time.

Time from Pathologist Ordered IHC Stain to Instrument

Verification

Figure 1 shows the distribution of “LIS Ordered to Instrument

Verification” times, for those verified within 12 hours, for each of the

three IHC work cell conditions described in Table 3 above (A, B, C).

Condition C illustrates that with workflow consulting and single piece

flow instrumentation, the time interval between placing an order

and instrument verification decreased, resulting in more of the daily

workload being processed sooner.

All B atch IHC P latforms

0

10

20

30

40

50

60

0 to 3 3 to 6 6 to 9 9 to 12

Hrs from IHC orde r to ve rified

% I

HC

Slid

e V

olum

e

50% Batch & 50% Continuous access IHC lnstruments before Workflow consulting

0

10

20

30

40

50

60

0 to 3 3 to 6 6 to 9 9 to 12

Hrs from IHC order to verified

% IH

C Sl

ide

Volu

mes

50% Batch & 50% Continuous access IHC Instruments after Workflow Consulting

0

10

20

30

40

50

60

0 to 3 3 to 6 6 to 9 9 to 12

Hrs from IHC order to verified

% IH

C Sl

ide

Volu

me

Figure 1.: Hours from LIS Order to Instrument Verified.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 18

©2011 Dark Intelligence Group, Inc.

More specifically, Condition C demonstrates a 50% increase in

cases verified within the first 3 hours of the first shift, and a 21%

increase in cases verified within the first 6 hours of the first shift.

The latter condition enabled IHC slide processing to begin earlier in

the lab shift, improving overall test turnaround time and freeing lab

personnel to attend to other value-added work streams.

In order to prove statistical significance, a Kruskal-Wallis test (non-

parametric analysis of variance) was used to evaluate the difference in

“Order Time to Instrument Verification” between the three conditions

(Table 5). This test exhibited a significant time savings, with the

median “Order Time to Verification” improved by 30 minutes to 1

hour, comparing condition C to conditions A and B. Respectively,

Wilcoxon rank-sum tests measuring each pair condition also indicated

a significant difference in “Order Time to Verification” under

condition C compared to conditions A and B.

Table 5. Median Time from LIS Order to Instrument Verified by Condition.

IHC Work Cell Time Period Median Range p-value

A Until October 2009 4.32 (4:19) 0.13-102.00 0.1736 (compared to B);<0.0001 (compared to C)

B October 2009 to January 2010

5.05 0.00-50.27 0.1736 (compared to A);<0.0001 (compared to C)

C January 2010 to April 2010

3.80 (3:48) 0.27-28.98 <0.0001 (compared to A);<0.0001 (compared to C)

(It) enabled IHC

slide processing

to begin earlier

in the lab shift,

improving

overall test

turnaround time

and freeing lab

personnel to

attend to other

value-added

work streams.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 19

©2011 Dark Intelligence Group, Inc.

Chapter 5

Results: Time from LIS Order to Run CompletionFigure 2 shows the distribution of workload, from “LIS Order to Run

Completion,” for each of the 3 conditions during a 15 hour period

of time. The time from “LIS Order to Run Completion” appears

similar between conditions A and B, with condition C showing a shift

towards earlier run completion for more of the workload.

As shown in Table 6, the percentage of slides completed within 3,

6, and 12 hours approximately doubled after performing workflow

optimization, with 73% of slides run within 12 hours.

Table 6. Volume of Slides Complete Over Time by IHC Work Cell Condition.

IHC Work Cell Time Period

Slides Run Within 3 hours

Slides Run Within 6 hours

Slides Run Within 12 hours

A Until October 2009

8% 22% 35%

B October 2009 to January 2010

2% 14% 41%

C January 2010 to April 2010

14%(75% improvement from A-C)

46%(109% improvement from A-C)

73%(109% improvement from A-C)

All Batch IHC Instruments

0

10

20

30

40

50

60

0 to 3 3 to 6 6 to 9 9 to 12 12 to 15

Hrs from IHC order to complete

% IH

C Sl

ide

Volu

me

50% Batch & 50% Continuous access IHC Instruments before Workflow Consulting

0

10

20

30

40

50

60

0 to 3 3 to 6 6 to 9 9 to 12 12 to 15

Hrs from IHC order to run complete

% IH

C Sl

ide

Volu

mes

50% Batch & 50% Continuous access IHC Instruments after Workflow Consulting

0

10

20

30

40

50

60

0 to 3 3 to 6 6 to 9 9 to 12 12 to 18

Hrs from IHC order to run complete

% IH

C Sl

ide

Volu

me

Figure 2.: Hours from LIS Order to Run Complete.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 20

©2011 Dark Intelligence Group, Inc.

In order to evaluate statistical significance, a Kruskal-Wallis test

was used to evaluate the overall difference in time from “LIS

Ordered to Slide Completed” between the three conditions. This test

indicated that there was a significant difference in time completed

between these three conditions, with the median time decreasing by

approximately 3 hours after workflow optimization. Wilcoxon rank-

sum tests comparing each pair of conditions indicated that there was a

significant difference in “LIS Order Time to Slide Completed” under

condition C, compared to conditions A and B (Table 7).

Table 7. Median Time from LIS Order to Run Complete by Condition.

IHC Work Cell Time Period Median Range p-value

A Until October 2009 9.88 0.93-103.00 0.6125 (compared to B);<0.0001 (compared to C)

B October 2009 to January 2010

9.45 1.33-50.63 0.6125 (compared to A);<0.0001 (compared to C)

C January 2010 to April 2010

6.62 1.18-34.30 <0.0001 (compared to A);<0.0001 (compared to C)

The median time

decreased by

approximately

3 hours after

workflow

optimization.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 21

©2011 Dark Intelligence Group, Inc.

Chapter 6

Results: Improved Productivity� in the IHC Work CellProcessing 77% of CCF’s total IHC volume in single piece flow

mode on the BenchMark ULTRA staining platform resulted in

increased slide throughput, which translated to an additional IHC

order cutoff time for slide processing at 4 p.m. Table 8 shows the

new IHC order cutoff times that were established due to this study.

Workflow consulting identified opportunities for pulling a portion

of the overnight IHC slide processing into the evening shift on the

BenchMark ULTRA platforms. This workload shift was the most

significant efficiency gain.

Pathologists could now have 33% more of their daily slide volume

at 12:00 midnight rather than waiting until 10:30 a.m. The lab also

recognized a substantial time-savings benefit with the implementation

of the BenchMark ULTRA platforms through a decrease in the

pre-run slide sorting, a non-value added activity associated with

slide batching. With the 50 highest volume tests residing on the

BenchMark ULTRA, sorting was reduced to only those slides run on

a BenchMark XT instrument, or 23% of the workload.

Table 8. IHC Batch Order Cutoff and Slide Run Times (BenchMark ULTRA single piece flow staining platform and optimized workflow).

IHC Order Cutoff Time

Average Slide Start Time

Average Slide Completion Time

Slides Delivered to Pathologist

10:00 a.m. 11:00 a.m. 1:15 p.m. 3-4 p.m.

1:00 p.m. 2:00 p.m. 5:15 p.m. 7-8 p.m.

4:00 p.m. 6:30 p.m. 9:45 p.m. 12:00 midnight

After 4:00 p.m. Overnight shift run Overnight 10 a.m. (next day)

Pathologists

could now have

33% more of

their daily slide

volume at 12:00

midnight rather

than waiting

until 10:30 a.m.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 22

©2011 Dark Intelligence Group, Inc.

ConclusionsOptimizing the mix of IHC staining platforms and incorporating

Lean workflow processes within the IHC work cell delivered

significant improvements to the test turnaround time, extension of

test ordering (cutoff times), and increased slide-throughput per full

time employee (FTE). Workflow consultation and the incorporation

of Lean workflow concepts to the lab processes can add to the overall

slide processing efficiency gains found with the implementation of the

BenchMark ULTRA single piece flow slide-staining platform.

The workflow plan, in conjunction with the addition of the

BenchMark ULTRA platforms, reduced batching and increased the

continuous flow of specimens. Workflow optimization decreased

IHC turnaround times, reduced the time required to manage and

batch load stainers, supported and smoothed fluctuations in specimen

flow, and enabled the lab to increase throughput by integrating

Lean concepts such as single piece flow with single piece flow

instrumentation. The mix of instrumentation and optimized resource

allocation, jointly, facilitated extended IHC order cutoff times to

4 p.m. (from 1:00 p.m.), effectively providing an additional 33% of

slides available for sign-out by 12:00 midnight.

The implementation of a single-piece flow, single-piece flow IHC

platform, and integration of Lean methodology to the IHC work cell

enabled Cleveland Clinic Foundation to increase slide throughput,

expand test menu availability on the instruments, extend order

cutoff times, improve slide turnaround time, reduce manual sorting

processes, and reallocate FTE time to value-added activities, resulting

in significant advancements for laboratory productivity and process.

The workflow

plan, in

conjunction with

the addition of

the Benchmark

ULTRA

platforms,

reduced

batching and

increased the

continuous flow

of specimens.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 23

©2011 Dark Intelligence Group, Inc.

References1. Beusa, Rene J., Adapting lean to histology laboratories. Annals

of Diagnostic Pathology. 13 (2009) 322-333.

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©2011 Dark Intelligence Group, Inc.

Appendices

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©2011 Dark Intelligence Group, Inc.

Erika Klohe, Senior Product Manager supporting IHC and ISH staining solutions, comes to Ventana Medical Systems, Inc. with over ten years of experience in product development, marketing and project management. Erika’s diverse background in cancer diagnostic applications furthers the Ventana mission to improve the lives of all patients afflicted with cancer. Helping to outfit anatomic pathology laboratories with best-in-class automated instrumentation and reagents, Erika contributes to the global effort to empower cancer intelligence.

Claudiu V. Cotta, MD, PhD, is the Medical Director of the Cleveland Clinic immunohistochemistry lab. Dr. Cotta received his medical degree from Universitatea de Medicina si Farmacie Targu-Mures in Romania, and his PhD from the University of Alabama at Birmingham. After a residency in anatomic and clinical pathology at the University of Alabama at Birmingham, Dr. Cotta completed fellowships in hematopathology at the University of Texas M.D. Anderson Cancer Center. Dr. Cotta’s professional interests are hematopathology, molecular pathology, and flow cytometry.

Amy Posch is the Lab Manager of the Cleveland Clinic immunohistochemistry lab. Amy is a Medical Technologist (MT). She has worked in the Cleveland Clinic laboratories for 32 years.

Renata Klinkosz has been a Medical Technologist, MT, for 25 years. Renata has worked in the Cleveland Clinic immunohistochemistry lab for 15 years.

Elizabeth Rowe has been a Histology Technologist for 40 years. Elizabeth has worked in the Cleveland Clinic laboratories for seven years.

Ma. Elena Magcamit-Labay has been a Medical Technologist, (AMT)MT and (ASCP)HTL for 15 years. Ellen has worked in the Cleveland Clinic laboratories for three years.

Fredericka Jones has been a Histology Technician for eight years. Fredericka joined the Cleveland Clinic team in September 2011.Michelle Wayman has been a Histology Technician (ASCP)HT for 20 years. Michelle has worked in the Cleveland Clinic laboratories for ten years.

Roderick Mangalindan has been a Medical Technologist, (AMT)MT and (ASCP)HTL for 28 years. Derick has worked in the Cleveland Clinic laboratories for six years.

Stephanie Sanchez is a Biostatistician at Ventana Medical Systems. She has an MPH in Biostatistics and has worked at Ventana for two years.

Kathleen Sergott is the Major Account Manager at Ventana Medical Systems, a subsidiary of Roche. Kathleen has a Bachelor of Science Degree. She has worked with the Cleveland Clinic Health System for the past 10 years and Ventana since 2007.

Sherri Lomayesva is a Senior Technical Writer at Ventana Medical Systems, Inc. Sherri is a certified histotechnician and has worked at Ventana for three years.

Clinton Yip is a Manager of Workflow Consulting for Ventana Medical Systems, a member of the Roche Group. Clinton is a certified Lean Six Sigma Master Black Belt and has worked for Ventana for the last three-and-a-half years.

Jeff Pearson is a cytotechnologist and has worked in cytology for 10 years. For the last three years, Jeff has been a Marketing Manager at Ventana Medical Systems, Inc.

Mark Torowus is a Marketing Manager at Ventana Medical Systems, Inc. He is a trained Cytotechnologist. Over the past 21 years, his experiences ranging from managing an Anatomic Pathology laboratory to commercial responsibilities in the field of anatomic pathology.

James Walker is a Workflow Consulting Senior Manager for Ventana-Roche Diagnostics. He is a Lean Six Sigma Master Black Belt and holds a degree in Mechanical Engineering and a Masters in Business Administration. He has worked for Ventana for three years.

Heather Free is a Biostatistician at Ventana Medical Systems. She has an MPH in Biostatistics and has worked at Ventana for three years.

A-1About The Authors

Erika Klohe

Claudiu V. Cotta, MD, PhD

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 26

©2011 Dark Intelligence Group, Inc.

Ventana Medical Systems, Inc. (“VMSI”), a member of the Roche

Group, innovates and manufactures instruments and reagents that

automate tissue processing and slide staining for cancer diagnostics.

VENTANA solutions are used in clinical histology and drug

development research laboratories worldwide. The company’s

intuitive, integrated staining and workflow management platforms

that optimize laboratory efficiencies to reduce errors support

diagnosis and inform treatment decisions for anatomic pathology

professionals. Together with Roche, VMSI is driving personalized

medicine through accelerated drug discovery and the development

of “companion diagnostics” to identify the patients most likely to

respond favorably to specific therapies. Visit www.ventana.com to

learn more.

VENTANA, the VENTANA logo, are trademarks of Roche.

VMSI Media Relations

Jacqueline Bucher Director, Corporate Communications Phone:

520-877-7288 e-mail: [email protected]

A-2About Ventana Medical Systems, Inc.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 27

©2011 Dark Intelligence Group, Inc.

“�Dark Daily is

a concise e-news/

management

briefing on

timely topics in

clinical

laboratory and

anatomic

pathology group

management. It

is a solution to

the dilemma

facing anyone in

the laboratory

profession.

DARK Daily is a concise e-news/management briefing on timely topics in clinical laboratory and anatomic pathology group manage-ment. It is a solution to the dilemma facing anyone in the laboratory profession. New developments, new technology, and changing healthcare trends make it imperative to stay informed to be success-ful. At the same time, the Internet, cell phones, blackberries, laptop computers and wireless devices are overwhelming any one individu-al’s ability to absorb this crushing Tsunami of data.

DARK Daily is a quick-to-read, easy-to-understand alert on some key development in laboratory medicine and laboratory manage-ment. It has no counterpart in the lab world. Why? Because it is produced and written by the experts at The Dark reporT and The Dark Intelligence Group, who know your world, understand your needs and provide you with concise, processed intelligence on only those topics that are most important to you!

You will find DARK Daily to also be an exceptionally valuable resource in laboratory and pathology management. Some of the lab industry’s keenest minds and most effective experts will be offering their knowledge, their insights and their recommendations on win-ning strategies and management methods. Many of these experts are unknown to most lab directors. As has proven true with The Dark reporT for more than a decade, DARK Daily will be your invalu-able— and unmatched—resource, giving you access to the knowl-edge and experience of these accomplished lab industry professionals.

A-3About DARK Daily

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 28

©2011 Dark Intelligence Group, Inc.

“�Membership

is highly-

prized by the

lab industry’s

leaders and

early adopters.

It allows

them to share

innovations and

new knowledge

in a confidential,

non-competitive

manner.

The Dark Intelligence Group, Inc., is a unique intelligence service, dedicated to providing high-level business, management and market trend analysis to laboratory CEOs, COOs, CFOs, pathologists and senior-level lab industry executives. Membership is highly-prized by the lab industry’s leaders and early adopters. It allows them to share innovations and new knowledge in a confidential, non-competitive manner. This gives them first access to new knowledge, along with the expertise they can tap to keep their laboratory or pathology organization at the razor’s edge of top performance.

It offers qualified lab executives, pathologists and industry vendors a rich store of knowledge, expertise and resources that are unavailable elsewhere. Since its founding in 1996, The Dark Intelligence Group and The Dark reporT have played in instrumental roles in support-ing the success of some of the nation’s best-performing, most profit-able laboratory organizations.

The Dark Intelligence Group (TDIG) is headquartered in Austin, Texas. This location makes it very accessible for any laboratory organization seeking input, insight and support in developing their business operations, creating effective business strategies and crafting effective sales and marketing programs that consistently generate new volumes of specimens and increasing new profits. The Dark Intelli-gence Group, Inc. owns and operates two Web sites in the TDIG Website network:

http://www.DarkReport.com

http://www.DarkDaily.com

A-4About The Dark Intelligence Group, Inc. and The Dark reporT

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 29

©2011 Dark Intelligence Group, Inc.

A-5About the Executive War College on Laboratory and Pathology Management

Every spring since 1996, the lab industry’s best and brightest gather at the Executive War College on Laboratory and Pathology Management to learn, to share and to network. Many consider it to be the premier source of innovation and excellence in laboratory and pathology management.

Each year, a carefully selected line-up of laboratory leaders and inno-vators tell the story of how their laboratories are solving problems, tackling the toughest challenges in lab medicine and seizing oppor-tunities to improve clinical care and boost financial performance. The Executive War College is the place to get practical advice and solutions for the toughest lab management challenges. A unique case study format brings participants face-to-face with their most success-ful peers. They tell, first hand, how their laboratory solved intractable problems and successfully used new technology.

Many lab management secrets are shared, along with specific “what-not-to-do’s” gained from hard-won experience! It’s not pie-in-the-sky theory, but useful knowledge that can be put to use in any lab. The Executive War College offers superlative networking, with lab administrators and pathologists attending from countries as far away as the United Kingdom, Germany, Brazil and Australia. It makes the Executive War College a melting pot for all the best ideas, new lab technologies and management strategies now reshaping the laboratory industry. It’s also become a recruiting ground used by headhunters and major lab organizations.

In the United Kingdom, The Dark Intelligence Group and the Association of Clinical Biochemists (ACB) have co-produced a meeting every February since 2003. Known at Frontiers in Laboratory Medicine (FiLM), it attracts laboratory leaders and inno-vators in the United Kingdom. Also featuring a case study format, this meeting pioneered the international laboratory side-by-side case study, where a North American laboratory and a United Kingdom laboratory prepare a comparison of best practices and an operational assessment of their two organizations.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 30

©2011 Dark Intelligence Group, Inc.

In September 2005, a laboratory management meeting called Executive Edge was conducted in Toronto, Ontario, Canada, by The Dark Intelligence Group and QSE Consulting. It provided pathologists and lab directors in Canada with a customized meeting devoted to the strategic and operational issues of laboratory management in Canada.

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 31

©2011 Dark Intelligence Group, Inc.

Mark Terry is a freelance writer and editor specializing in clinical

diagnostics, telemedicine and biotechnology. He worked for 18 years

in clinical genetics prior to turning to writing and has published over

600 magazine and trade journal articles, 13 books and more than a

dozen book-length market research reports and white papers related to

clinical diagnostics. He is a member of the Association of Health Care

Journalists and the Association of Genetic Technologists.

A-6About Mark Terry

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Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 32

©2011 Dark Intelligence Group, Inc.

www.darkdaily.com ©2011 Dark Intelligence Group, Inc.

Notes

Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 33

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Notes

Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 34

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Notes

Innovation in Immunohistochemistry ( IHC) Staining:Single Piece Flow IHC Slide Processing 35

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©2011 Dark Intelligence Group, Inc.

© 2011 by the Dark Intelligence Group, Inc.

Terms of Use: All rights reserved. No part of this report my be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, faxing, emailing, posting online, or by any information storage and retrieval system, without written permission from the Publisher.

All trademarks and brands referred to herein are the property of their respective owners.

Contact InformationThe Dark Intelligence Group, Inc.Customer Service800-560-636321806 Briarcliff DriveSpicewood, Texas 78669

Legal NoticesWhile all attempts have been made to verify information provided in this publication, neither the author nor the publisher assumes any responsibility for error, omissions or contrary interpretations of the subject matter contained herein.

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