CologuardTM
`
`sDNA-based Colorectal Cancer Screening Test
`Instructions for Use
`
`For in vitro diagnostic use
`
`Exact Sciences Corporation
`
`441 Charmany Drive
`
`Madison, WI 53719
`
`www.exactsciences.com
`
`(800) XXX-XXXX
`
`Exact
`
`Document Type: Labeling
`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
`
`1 | P a g e
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`Geneoscopy Exhibit 1081, Page 1
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`

`

`Table of Contents
`
`Intended Use and Indications for Use ........................................................................................ 6
`Contraindications ....................................................................................................................... 6
`Warnings and Precautions ......................................................................................................... 6
`Summary and Explanation of the Test ....................................................................................... 7
`Principles of the Procedure ........................................................................................................ 8
`Reagents ................................................................................................................................... 9
`DNA Capture Reagents (Exact Sciences, 100028) ............................................................. 9
`DNA Preparation Reagents (Exact Sciences, 100029).......................................................10
`QuARTS Assay Reagents (Exact Sciences, 100030).........................................................10
`Cologuard DNA Control Kit (Exact Sciences, 100074) .......................................................10
`Hemoglobin Assay Reagents (Exact Sciences, 100031)....................................................11
`Cologuard Hemoglobin Control Kit (Exact Sciences, 100073)............................................11
`Ancillary Materials and Bulk Assay Reagents ....................................................................11
`Procedural Warnings and Precautions...................................................................................12
`Reagent Warnings and Precautions...................................................................................12
`Instrument Warnings and Precautions ...............................................................................13
`Reagent Storage and Handling Requirements.......................................................................13
`Instrumentation......................................................................................................................14
`Specimen Collection and Preparation for Analysis ....................................................................15
`Cologuard Laboratory Procedure ..............................................................................................15
`Receipt of Cologuard Collection Kit .......................................................................................15
`Preparation of Stool Homogenate for DNA Testing................................................................16
`Assay Overview.....................................................................................................................17
`Example Cologuard Setup.....................................................................................................18
`DNA Capture.........................................................................................................................19
`Prepare Capture Beads .....................................................................................................19
`Prepare Samples and Perform DNA Capture.....................................................................19
`Prepare and Label Sample Tubes ..................................................................................19
`
`Prepare Supernatant ......................................................................................................20
`
`Capture Incubation .........................................................................................................21
`
`Exact
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`Document Type: Labeling
`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
`
`2 | P a g e
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`

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`DNA Preparation and QuARTS Assay...................................................................................22
`Automated DNA Preparation and QuARTS Assay Setup...................................................23
`Reagent Preparation ......................................................................................................23
`
`STARlet Setup................................................................................................................23
`
`DNA Preparation ............................................................................................................28
`
`QuARTS Plate Setup......................................................................................................28
`
`Run the QuARTS Plate ..................................................................................................29
`
`Hemoglobin Assay.................................................................................................................33
`Preparation of Hemoglobin Samples and Reagents...........................................................33
`Prepare Samples............................................................................................................33
`
`Prepare Hemoglobin Assay Reagents and STARlet.......................................................34
`
`STARlet Setup for Hemoglobin Assay ............................................................................35
`
`Wash Hemoglobin Assay Plate ......................................................................................35
`
`Automated Hemoglobin Plate Setup ..................................................................................36
`Hemoglobin Assay Procedure............................................................................................36
`Read Hemoglobin Plate .....................................................................................................37
`Hemoglobin Sample Storage .............................................................................................38
`Data Handling and Analysis ......................................................................................................39
`Review and Release Methylation, Mutation, or Hemoglobin Assay Results...........................39
`Review and Release Overall Cologuard Results ...................................................................42
`Interpretation of Results ............................................................................................................46
`Procedural Notes and Precautions............................................................................................46
`Additional Stool Homogenate Aliquots............................................................................46
`
`Insufficient Supernatant..................................................................................................46
`
`Enter Supplementary Lot Information .............................................................................47
`
`Prepare Capture Beads (for >6 tubes)............................................................................47
`
`Procedure for Performing Partial Runs ...........................................................................47
`
`Quality Control ..........................................................................................................................48
`Process Controls ............................................................................................................48
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`Exact
`
`Document Type: Labeling
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`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
`
`Geneoscopy Exhibit 1081, Page 3
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`

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`Lot Matching and Sample Tracking during Processing ...................................................48
`
`Review and Release Cologuard Results.........................................................................48
`
`Troubleshooting Guide..............................................................................................................49
`DNA Capture .....................................................................................................................49
`Centrifuged Stool Sample Abnormalities ........................................................................49
`
`Incomplete Dispersion of Inhibitor Removal Tablet.........................................................49
`
`Broken Spin Filter...........................................................................................................49
`
`Capture Incubator Produces Error Message...................................................................49
`
`Capture Aspirator Produces Error Message ...................................................................50
`
`Incomplete Aspiration of Supernatant.............................................................................50
`
`Sample Appears Gelatinous After Aspiration..................................................................50
`
`Beads Not Fully Suspended After Shaking .....................................................................50
`
`DNA Preparation and QuARTS Assay ...............................................................................50
`Methylation/Mutation Setup Run Aborts..........................................................................50
`
`Hemoglobin Assay .............................................................................................................51
`Hemoglobin Setup Run Aborts .......................................................................................51
`
`Retest Hemoglobin Sample Tubes .................................................................................51
`
`Procedural Limitations...............................................................................................................51
`Performance Characteristics.....................................................................................................52
`Clinical Cutoff ........................................................................................................................52
`Analytical Sensitivity ..............................................................................................................52
`Specificity and Cross-Reactivity.............................................................................................53
`Precision and Reproducibility ................................................................................................55
`Robustness ...........................................................................................................................59
`Interfering Substances...........................................................................................................60
`Carry-over and Cross-contamination Cologuard Testing .......................................................61
`Stability Studies.....................................................................................................................62
`Clinical Sensitivity and Specificity..........................................................................................64
`Abbreviations Used...................................................................................................................83
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`Exact
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`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
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`Key Symbols Used....................................................................................................................83
`References ...............................................................................................................................84
`Contact Information...................................................................................................................84
`Trademarks...............................................................................................................................84
`Patents .....................................................................................................................................84
`Limited License.........................................................................................................................85
`Warranty ...................................................................................................................................85
`Copyright ..................................................................................................................................85
`
`Exact
`
`Document Type: Labeling
`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
`
`5 | P a g e
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`Geneoscopy Exhibit 1081, Page 5
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`

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`Intended Use and Indications for Use
`Intended Use
`Cologuard is intended for the qualitative detection of colorectal neoplasia associated DNA
`markers and for the presence of occult hemoglobin in human stool. Cologuard is for use with the
`Cologuard collection kit and the following instruments: BioTek ELx808 Absorbance Microplate
`Reader; Applied Biosystems® 7500 Fast Dx Real-Time PCR; Hamilton Microlab® STARlet;
`and the Exact Sciences System Software with Cologuard Test Definition.
`
`Indications for Use
`Cologuard is intended for the qualitative detection of colorectal neoplasia associated DNA
`markers and for the presence of occult hemoglobin in human stool. A positive result may
`indicate the presence of colorectal cancer (CRC) or advanced adenoma (AA) and should be
`followed by diagnostic colonoscopy. Cologuard is indicated to screen adults of either sex, 50
`years or older, who are at typical average-risk for CRC. Cologuard is not a replacement for
`diagnostic colonoscopy or surveillance colonoscopy in high risk individuals.
`
`Contraindications
`Cologuard is intended for use with patients, age 50 years and older, at average risk who are
`typical candidates for CRC screening. Cologuard was not clinically evaluated for the following
`types of patients:
`o Patients with a history of colorectal cancer, adenomas, or other related cancers.
`o Patients who have had a positive result from another colorectal cancer screening
`method within the last 6 months.
`o Patients who have been diagnosed with a condition that is associated with high risk for
`colorectal cancer. These include but are not limited to:
`
`Inflammatory Bowel Disease (IBD)
`•
`• Chronic ulcerative colitis (CUC)
`• Crohn’s disease
`• Familial adenomatous polyposis (FAP)
`• Family history of colorectal cancer
`o Patients who have been diagnosed with a relevant familial (hereditary) cancer
`syndrome, such as Hereditary non-polyposis colorectal cancer syndrome (HNPCCC or
`Lynch Syndrome), Peutz-Jeghers Syndrome, MYH-Associated Polyposis (MAP),
`Gardner’s syndrome, Turcot’s (or Crail’s) syndrome, Cowden’s syndrome, Juvenile
`Polyposis, Cronkhite-Canada syndrome, Neurofibromatosis, or Familial Hyperplastic
`Polyposis.
`Warnings and Precautions
`
`o The performance of Cologuard has been established in a cross sectional study (i.e.,
`single point in time). Programmatic performance of Cologuard (i.e., benefits and risks
`with repeated testing over an established period of time) has not been studied.
`
`Exact
`
`Document Type: Labeling
`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
`
`6 | P a g e
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`

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`Performance has not been evaluated in adults who have been previously tested with
`Cologuard. Non-inferiority or superiority of Cologuard programmatic sensitivity as
`compared to other recommended screening methods for CRC and AA has not been
`established.
`o CRC screening guideline recommendations vary for persons over the age of 75. The
`decision to screen persons over the age of 75 should be made on an individualized
`basis in consultation with a healthcare provider. Cologuard test results should be
`interpreted with caution in older patients as the rate of false positive results increases
`with age.
`o A negative Cologuard test result does not guarantee absence of cancer or advanced
`adenoma. Patients with a negative Cologuard test result should be advised to continue
`participating in a colorectal cancer screening program with another recommended
`screening method. The screening interval for this follow-up has not been established.
`o Cologuard may produce false negative or false positive results. A false positive result
`occurs when Cologuard produces a positive result, even though a colonoscopy will not
`find cancer or precancerous polyps. A false negative result occurs when Cologuard does
`not detect a precancerous polyp or colorectal cancer even when a colonoscopy identifies
`the positive result.
`o Patients should not provide a sample for Cologuard if they have diarrhea or if they have
`blood in their urine or stool (e.g., from bleeding hemorrhoids, bleeding cuts or wounds on
`their hands, rectal bleeding, or menstruation).
`o To ensure the integrity of the sample, the laboratory must receive the patient specimens
`within 72 hours of collection. Patients should send stool samples to the laboratory
`according to the instructions stated in the Cologuard Patient Guide.
`o Patients should be advised of the caution listed in the Cologuard Patient Guide. Patients
`should NOT drink the preservative liquid.
`o The risks related to using the Cologuard Collection Kit are low, with no serious adverse
`events reported among people in a clinical trial. Patients should be careful when opening
`and closing the lids to avoid the risk of hand strain.
`Summary and Explanation of the Test
`Cologuard utilizes a multi-target approach to detect DNA and hemoglobin markers associated
`with colorectal cancer (CRC), as well as pre-malignant colorectal neoplasia. Three independent
`categories of biomarkers are targeted and provide an additive association with CRC and pre-
`malignant neoplasms.
`
`The first category of biomarkers involves epigenetic DNA changes characterized by aberrant
`gene promoter
`region methylation. The specific methylated gene targets include N-Myc
`Downstream-Regulated Gene 4 (NDRG4) and Bone Morphogenetic Protein 3 (BMP3).6,7
`NDRG4 and BMP3 have been shown to be hypermethylated in colorectal cancer.5,6 The
`Cologuard procedure incorporates bisulfite conversion of non-methylated cytosine residues to
`uracil
`in the DNA sequence to enable sensitive detection of hypermethylated NDRG4 and
`BMP3.
`
`Exact
`
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`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
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`The second category targets specific DNA point mutations in the v-Ki-ras2 Kirsten rat sarcoma
`viral oncogene homolog (KRAS) gene, which encodes a small GTPase that
`is activated
`transiently as a response to extracellular stimuli or signals.8,9,10 KRAS mutations have been
`detected in up to 35% of colorectal cancers and the 7 mutations in Exon 2 detected by
`Cologuard account for 98% of these KRAS mutations.12 KRAS mutations, along with NDRG4
`and BMP3 methylation markers, have been shown to be detected in the stool of subjects with
`colorectal neoplasia, including subjects with colorectal cancer and pre-malignant lesions.4,11
`
`The third category of biomarker is non-DNA based and detects hemoglobin, which can be
`associated with colonic bleeding. Results from the methylation, mutation, and hemoglobin
`assays are integrated by the Exact Sciences Analysis Software to determine a Positive or
`Negative reportable result or invalid result.
`
`Principles of the Procedure
`Cologuard is designed to analyze patients’ stool for the presence of DNA and hemoglobin
`markers, which may indicate the presence of colorectal cancer or pre-cancerous lesions.
`Patients use the Cologuard Collection Kit, consisting of a Container for collection of stool for
`DNA testing and a separate sampler (Tube) for collection of stool for hemoglobin testing. Both
`of these stool samples are required to obtain a Cologuard result.
`
`In the processing procedure for DNA testing, the stool sample is mixed with buffer in the
`Container using the Sample Mixer. An aliquot of the buffered stool sample is centrifuged to
`pellet solids and generate supernatant. The assay procedure begins with treatment of the
`supernatant with an Inhibitor Removal Tablet to remove inhibitors that may affect the detection
`of the DNA biomarkers. Treated supernatant is then combined with denaturing reagents and
`incubated with target-specific magnetic particles using the Capture Incubator instrument to
`capture sequences for NDRG4, BMP3, KRAS, and ACTB (reference gene).
`
`Using automated processes in the Capture Aspirator and Hamilton Microlab® STARlet
`(STARlet) instruments, targeted sequences are separated from the solution, washed, and eluted
`from the particles. Eluted DNA is split to provide two separate DNA aliquots for performing the
`methylation and mutation assays. The aliquot for the methylation assay is treated with bisulfite
`conversion reagents. Both aliquots are further purified with silica-coated magnetic beads from
`which DNA is eluted.
`
`The Quantitative Allele-specific Real-time Target and Signal Amplification (QuARTS(cid:140))
`technology combines real-time PCR and invasive cleavage to perform allele-specific
`amplification and detection of methylated target DNA (NDRG4, BMP3) and specific DNA point
`mutations (KRAS) in the molecular assays. Each purified DNA aliquot
`is mixed with the
`appropriate QuARTS reaction master mix. The bisulfite-converted DNA is mixed with a master
`mix for the NDRG4, BMP3, and ACTB QuARTS reaction. The unconverted, purified DNA for
`KRAS detection is mixed with a master mix for the 7 KRAS mutations and ACTB. Both QuARTS
`reactions are processed using a real-time cycler in the same assay plate with the same cycling
`and detection program. Each assay for the NDRG4, BMP3, ACTB, and KRAS markers is
`monitored separately through an independent fluorescent detection channel.
`
`Exact
`
`Document Type: Labeling
`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
`
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`Geneoscopy Exhibit 1081, Page 8
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`

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`In a parallel workflow, the hemoglobin assay stool sample is prepared and analyzed in a
`quantitative Enzyme-Linked Immunosorbent Assay (ELISA) that determines the concentration of
`hemoglobin in the sample. Each sample is incubated in a single well of a 96-well plate coated
`with anti-hemoglobin antibody, which is then washed to remove any unbound material. A
`second anti-hemoglobin antibody conjugated to the enzyme horseradish peroxidase (HRP) is
`then added to the wells and incubated with a colorimetric substrate for HRP. After the reaction is
`stopped and the optical density read on a plate reader, the level of hemoglobin present in the
`stool sample is calculated using a calibration curve prepared from a set of calibrators with
`known hemoglobin concentrations.
`
`Run control samples for both the molecular assays and hemoglobin assay are tested along with
`patient samples to show that the process has been performed appropriately. Run controls from
`the Cologuard DNA Control Kit (Exact Sciences, 100074) and Cologuard Hemoglobin Control
`Kit (Exact Sciences, 100073) are required in each run to obtain valid assay results. Results from
`the methylation, mutation, and hemoglobin assays are integrated by the Exact Sciences
`Analysis Software to determine a Positive or Negative reportable result or an Invalid result.
`
`Reagents
`Cologuard utilizes several reagent kits stored at different temperatures including DNA Capture
`Reagents (2 to 8°C), DNA Preparation Reagents (15 to 30°C), QuARTS Assay Reagents (-25 to
`-15°C), and Hemoglobin Assay Reagents (2 to 8°C).
`
`Lots of reagents are matched for performing the assay. A Supplemental Lot Information sheet is
`supplied with the reagents. On the sheet is a 2D barcode or set of barcodes, the Supplemental
`Lot Information Barcode (SLIB), which includes calibration and lot matching information for that
`set of reagents. The SLIB is scanned into the Exact Sciences Analysis Software prior to
`performing any portion of the automated run using these reagents.
`
`Use lot numbers of reagents and calibrators listed in Supplemental Lot Information together. DO
`NOT mix or substitute reagents from Supplemental Lot Information containing different lot groupings.
`
`Ancillary and bulk assay reagents (stored at 15 to 30°C) are also required to run Cologuard.
`Bulk assay reagents are not lot matched to Cologuard reagents and may be used with any lot of
`reagent kits.
`
`DNA Capture Reagents (Exact Sciences, 100028)
`Component
`Part #
`Description
`
`200150
`
`CAP BDS, Capture Beads
`
`Magnetic particles with covalently
`bound oligonucleotide probes
`
`Amount
`
`7 mL
`
`#
`provided
`10
`
`Exact
`
`Document Type: Labeling
`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
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`

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`DNA Preparation Reagents (Exact Sciences, 100029)
`Component
`Part #
`Description
`
`200123
`200124
`
`200125
`200222
`
`200127
`200218
`
`0.1 M NaOH solution
`Ammonium bisulfite solution
`
`DEN SLN, Denaturation Solution
`BIS SLN, Bisulfite Conversion
`Solution
`NEU SLN, Neutralization Solution Potassium Acetate solution
`DES SLN, Desulphonation
`0.35 M NaOH solution
`Solution (Concentrate)
`BND BDS, Binding Beads
`DNA and QuARTS Supplementary
`Lot Information
`
`Magnetic silica particles
`n/a
`
`QuARTS Assay Reagents (Exact Sciences, 100030)
`Description
`
`Component
`Part #
`CAR SLN, Carrier Solution
`200235
`ELU BFR, Elution Buffer
`200130
`200131 MIX A, Oligo Mix A, Methylation
`
`200132 MIX B, Oligo Mix B, Mutation
`ENZ, Enzyme Mix
`200133
`D CAL 1, DNA Calibrator 1,
`200134
`High Methylation
`D CAL 2, DNA Calibrator 2,
`Low Methylation
`D CAL 3, DNA Calibrator 3,
`High Mutation
`D CAL 4, DNA Calibrator 4,
`Low Mutation
`
`200135
`
`200136
`
`200137
`
`Bovine Serum Albumin, Tris, EDTA
`Tris, EDTA Solution
`Oligonucleotides, FRET probes,
`dNTPs
`Oligonucleotides, FRET probes,
`dNTPs
`Enzymes in a buffer with glycerol
`NDRG4, BMP3, ACTB DNA in buffer
`with non-human DNA carrier
`NDRG4, BMP3, ACTB DNA in buffer
`with non-human DNA carrier
`KRAS, ACTB DNA in buffer with non-
`human DNA carrier
`KRAS, ACTB DNA in buffer with non-
`human DNA carrier
`
`Cologuard DNA Control Kit (Exact Sciences, 100074)
`Component
`Part #
`Description
`
`200139
`
`200140
`
`200141
`
`200315
`
`DNA Control 1, High
`
`DNA Control 2, Low
`
`DNA Control 3, Negative
`
`DNA Control Kit Supplementary
`Lot Information Barcode
`
`Oligonucleotides, Tris, EDTA with
`Carrier DNA
`Oligonucleotides, Tris, EDTA with
`Carrier DNA
`Oligonucleotides, Tris, EDTA with
`Carrier DNA
`n/a
`
`Amount
`
`14.5 mL
`8.5 mL
`
`8.5 mL
`7.5 mL
`
`8.4 mL
`1 each
`
`Amount
`1600 μL
`12.5 mL
`1200 μL
`
`1200 μL
`250 μL
`60 μL
`
`60 μL
`
`60 μL
`
`60 μL
`
`Amount
`
`15 mL
`
`15 mL
`
`15 mL
`
`1 each
`
`#
`provided
`10
`10
`10
`10
`10
`
`1
`
`#
`provided
`10
`10
`10
`
`10
`10
`10
`
`10
`
`10
`
`10
`
`#
`provided
`10
`
`10
`
`10
`
`1
`
`Exact
`
`Document Type: Labeling
`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
`
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`Geneoscopy Exhibit 1081, Page 10
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`

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`Hemoglobin Assay Reagents (Exact Sciences, 100031)
`Component
`Part #
`Description
`
`200142
`
`200143
`200144
`
`200100
`200101
`200146
`
`200219
`
`Hb PLATE, Hemoglobin Assay
`Plate
`SMP BFR, Sample Buffer
`CONJ, Antibody Conjugate
`
`SUBS, Substrate
`STP SLN, Stop Solution
`Hb CAL, Hemoglobin Assay
`Calibrator
`Hemoglobin Assay
`Supplementary Lot Information
`
`Mouse anti-Human Hemoglobin
`Antibody coated plate
`Tris, NaCl, casein
`Mouse anti-Human Hemoglobin
`Antibody-HRP Conjugate
`Tetramethylbenzidine in buffer
`Acidic Buffered Solution
`Human Hemoglobin, buffer
`(lyophilized)
`n/a
`
`Cologuard Hemoglobin Control Kit (Exact Sciences, 100073)
`Component
`Part #
`Description
`
`200147
`
`200148
`
`200149
`
`20031e
`
`Hemoglobin Control 1, High
`
`Hemoglobin Control 2, Low
`
`Human Hemoglobin, buffer
`(lyophilized)
`Human Hemoglobin, buffer
`(lyophilized)
`Hemoglobin Control 3, Negative Human Hemoglobin, buffer
`(lyophilized)
`
`Hemoglobin Control Kit
`Supplementary Lot Information
`Barcode
`
`n/a
`
`Amount
`
`1 plate
`
`12 mL
`12 mL
`
`12 mL
`12 mL
`1 each
`
`1 each
`
`Amount
`
`1 each
`
`1 each
`
`1 each
`
`1 each
`
`#
`provided
`5
`
`5
`5
`
`5
`5
`5
`
`1
`
`#
`provided
`5
`
`5
`
`5
`
`1
`
`Ancillary Materials and Bulk Assay Reagents
`Required ancillary materials, kits and bulk assay reagents are available using the part numbers
`listed below.
`
`Part #
`
`Component
`
`Description
`
`STL BFR, Stool Buffer
`
`Tris, EDTA Solution
`
`TABLT, Inhibitor Removal Tablet
`
`Polyvinylpolypyrrolidone with excipient
`
`FILT, Spin Filter
`
`TUBES, Barcoded Mixing Tubes
`
`PRE WSH, Capture Bead Pre-
`wash
`CAP SLN, Capture Solution
`
`Spin filters for 50 mL tubes
`
`Empty barcoded tubes
`
`Sodium Bicarbonate Buffer
`
`Guanidine Thiocyanate
`
`Document Type: Labeling
`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
`
`20020
`4
`20015
`1
`20013
`8
`20015
`2
`20012
`0
`20012
`1
`
`Exact
`
`Am
`oun
`t
`per
`ves
`sel
`
`20 L
`
`95 ea
`
`46 ea
`
`50 ea
`
`350 mL
`
`450 mL
`
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`

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`20012
`2
`20012
`6
`20012
`9
`20014
`5
`
`CAP WSH, Capture Wash
`
`BND SLN, Binding Solution
`
`CNV WSH, Conversion Wash
`Concentrate
`Hb WSH, Hemoglobin Assay
`Wash Concentrate
`
`MOPS Buffer, NaCl
`
`Guanidine Hydrochloride
`
`Tris Buffer
`
`Phosphate Buffer with detergent
`
`450 mL
`
`450 mL
`
`200 mL
`
`300 mL
`
`Procedural Warnings and Precautions
`
`(cid:131)
`
`Warnings and notes emphasize important reagent information and critical instructions for safely
`performing laboratory procedures.
`(cid:131) Use standard laboratory precautions in accordance with applicable federal, state, and
`local regulations.
`Laboratory areas should be cleaned and maintained according to good laboratory
`practices for clinical
`laboratories processing biological specimens. Appropriate
`procedures shall be defined by the laboratory director.
`(cid:131) Sodium hypochlorite may not be appropriate for decontamination of instruments and
`pipettes.
`(cid:131) Refer to user’s manuals for complete decontamination procedures for instruments and
`equipment.
`(cid:131) Product components (residual product, packaging, waste) can be considered laboratory
`waste. Dispose in accordance with applicable federal, state, and local regulations.
`
`Reagent Warnings and Precautions
`
`For In vitro diagnostic use
`
`Users should familiarize themselves with the instructions contained in the Cologuard Patient Guide,
`this booklet and the equipment used to perform the Cologuard prior to use.
`
`Caution: Patients should avoid bringing preservative solution in contact with skin or eyes. Irritation
`could result.
`
`Some reagents or waste are potentially corrosive or flammable. Dispose of all reagents in accordance
`with local, state, and Federal regulations. (CLSI doc GP5-A2, EPA/530-SW-86-014)
`
`Warning, biological hazard. Specimens may be infectious. Only personnel adequately trained in
`handling infectious materials should be permitted to perform this diagnostic procedure. Human
`materials used in Hemoglobin Assay Calibrator were tested and found to be negative for HIV, Hepatitis
`B and Hepatitis C. As an additional precaution, Hemoglobin Assay Calibrator (Hb CAL) should be
`treated as potentially infectious. Dispose of all potentially biohazardous materials in accordance with
`local, state and Federal regulations.
`Danger, Corrosive. Skin and respiratory Irritant. Avoid contact with Denaturation Solution (DEN SLN),
`Bisulfite Conversion Solution (BIS SLN), and Desulphonation Solution (DES SLN) with skin, eyes, and
`mucous membranes. If these fluids come into contact with skin or eyes, wash with water. If spills of
`these fluids occur, dilute with water before wiping dry.
`
`Exact
`
`Document Type: Labeling
`DOC NO: LBL-0209 REVISION: 1
`Cologuard(cid:140) Instructions For Use
`Effective Date: TBD
`
`12 | P a g e
`
`Geneoscopy Exhibit 1081, Page 12
`
`

`

`Warning, Irritant. Avoid contact with Binding Solution (BND SLN), Capture Solution (CAP SLN) and
`Stop Solution (STP SLN) with skin, eyes and mucous membranes. If these fluids come into contact
`with skin or eyes, wash with water. If swallowed, DO NOT induce vomiting unless directed by poison
`control center. If spills of these fluids occur, dilute with water before wiping dry.
`Warning, Respiratory irritant. Avoid contact with Bisulfite Conversion Solution (BIS SLN) with skin, eyes
`and mucous membranes. If these fluids come into contact with skin or eyes, wash with water. If spills of
`these fluids occur, dilute with water before wiping dry. If swallowed, DO NOT induce vomiting unless
`directed by poison control center. If inhaled, move to fresh air. If breathing becomes difficult, give
`oxygen and consult physician.
`The Antibody Conjugate (CONJ) may conta