InSure ONE

K170548 · Enterix, Inc. · KHE · Oct 5, 2017 · Hematology

Device Facts

• Record ID: K170548
• Device Name: InSure ONE
• Applicant: Enterix, Inc.
• Product Code: KHE · Hematology
• Decision Date: Oct 5, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.6550
• Device Class: Class 2

Indications for Use

The InSure® ONE™ is a fecal immunochemical test (FIT) that qualitatively detects human hemoglobin from blood in fecal samples. The samples will generally be collected by the test subject at home and the test developed at laboratories or professional offices. The InSure® ONE™ test is used to aid in the detection of lower gastrointestinal bleeding.

Device Story

InSure® ONE™ is a fecal immunochemical test (FIT) for detecting lower gastrointestinal bleeding. Patient collects fecal water sample from toilet bowl using long-handled brushes; sample applied to test card; card serves as transport medium to laboratory. Laboratory/professional staff develop test using InSure® ONE™ Test Strips and Run Buffer. Test strips utilize mouse monoclonal anti-human hemoglobin antibodies and colloidal gold particles for visual detection. Device provides qualitative result indicating presence of human hemoglobin. Facilitates screening for gastrointestinal pathology; enables home-based sample collection; simplifies procedure compared to multi-day sampling.

Clinical Evidence

Clinical study of 859 patients (ages 20–93) with various GI symptoms or history of colorectal disease. Patients collected samples using both the predicate (Test Card A) and the subject device (Test Cards B and C) prior to colonoscopy. Histopathology was used as the reference standard. Results showed acceptable agreement between the subject device and the predicate. For colorectal cancer, the subject device demonstrated 100% positive percent agreement with the predicate. The study concluded that the new sampling method (two aliquots from one bowel movement) is equivalent to the predicate method (one aliquot from two bowel movements).

Technological Characteristics

Lateral flow chromatographic immunoassay. Components: Test card, test strips (mouse monoclonal anti-hHb test line, donkey anti-goat control line, colloidal gold-labeled anti-hHb polyclonal antibodies), and run buffer (borate salts, ethanol, bovine serum albumin, sodium azide). Qualitative detection of hHb. Assay cut-off: 50 μg Hb/g stool. Manual sample collection and visual interpretation.

Indications for Use

Indicated for the qualitative detection of human hemoglobin in fecal samples to aid in the detection of lower gastrointestinal bleeding. Suitable for use by patients for home sample collection and by laboratory/professional staff for test development.

Regulatory Classification

Identification

An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood is blood present in such small quantities that it can be detected only by chemical tests of suspected material, or by microscopic or spectroscopic examination.)

Special Controls

*Classification.* Class II (special controls). A control intended for use with an occult blood test is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.

Predicate Devices

• InSure® FIT™ (Fecal Immunochemical Test)

Reference Devices

• FOBT Controls (K101831)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K170548

B. Purpose for Submission:
To modify the fecal sample collection procedure

C. Measurand:
Human hemoglobin (hHb) in feces

D. Type of Test:
Lateral flow chromatographic immunoassay

E. Applicant:
Enterix Inc., A Clinical Genomics Inc. Company

F. Proprietary and Established Names:
InSure ONE – One Day Fecal Immunochemical Test

G. Regulatory Information:

1. Regulation section:
21 CFR 864.6550, Occult blood test

2. Classification:
Class II

3. Product code:
KHE, Reagent, Occult Blood

4. Panel:
Hematology (81)

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H. Intended Use:

1. Intended use:

The InSure ONE is a fecal immunochemical test (FIT) that qualitatively detects human hemoglobin from blood in fecal samples. The samples will generally be collected by the test subject at home and the test developed at laboratories or professional offices. The InSure ONE test is used to aid in the detection of lower gastrointestinal bleeding.

2. Indication(s) for use:

Same as Intended Use

3. Special conditions for use statement(s):

For prescription use and over-the-counter (sample collection kit)

4. Special instrument requirements:

Not applicable

I. Device Description:

The InSure ONE – One Day Fecal Immunochemical Test qualitatively detects human hemoglobin from blood in fecal samples. The fecal sample is generally collected by the test subject at home. Stool samples in toilet bowl water are collected using long handled brushes to collect a small volume of water from around the defecated stool. Once collected, the stool sample is placed on an InSure ONE Test Card. The InSure ONE Test Card then serves as a means to transport the dried stool sample to the laboratory. The test reaction is developed in the clinical laboratory or medical professional office with appropriate quality control.

Components of InSure ONE – One Day Fecal Immunochemical Test:

a. The InSure ONE Collection Kit contains:

- InSure ONE Instructions for Use-Patient
- InSure ONE Test Card
- Brush Kit containing 2 brushes and a waste bag
- Business reply form and envelope

b. The InSure ONE Developer Components (for development and interpretation of the test) contains:

- InSure ONE Instructions for Use-Professional Laboratory

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- InSure Test Strips: The Test Strips contain a mouse monoclonal anti-human hemoglobin Test Line and a conjugate-specific polyclonal (donkey anti-goat) antibody Control Line and a conjugate of anti-human hemoglobin polyclonal antibodies bound to colored (colloidal gold) particles.
- InSure Run Buffer: Contains borate salts, ethanol, bovine serum albumin, and sodium azide as preservative.

# J. Substantial Equivalence Information:

1. Predicate device name(s):

InSure FIT Fecal Immunochemical Test

2. Predicate 510(k) number(s):

K002457

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device InSure ONE – One Day Fecal Immunochemical Test, K170548 | Predicate InSure FIT Fecal Immunochemical Test, K002457 |
| Intended Use | The InSure ONE is a fecal immunochemical test (FIT) that qualitatively detects human hemoglobin from blood in fecal samples. The samples will generally be collected by the test subject at home and the test developed at laboratories or professional offices. The InSure ONE test is used to aid in the detection of lower gastrointestinal bleeding. | InSure™ FOBT is an immunochromatographic fecal occult blood test that detects human hemoglobin from blood in fecal samples. The samples will generally be collected by the test subject at home and the test developed at laboratories or professional offices. The InSure™ FOBT sample collection kit, consisting of a) Test Kit Envelope, b) Instructions for Use; c) Test Card, d) Brush Kit, e) Reply Form, f) Return Envelope, and g) Screening for Life brochure, is intended for Over-The-Counter distribution. Fecal occult blood test are useful screening aids for detecting primarily lower gastrointestinal (g.i.) disorders that may be related to iron deficiency anemia, diverticulitis, ulcerative colitis, polyps, adenomas, colorectal cancers or other g.i. lesions that can bleed. InSure™ FOBT is recommended for use by health professionals as part of routine physical examinations and in |

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| Similarities | | |
| --- | --- | --- |
| Item | Device
InSure ONE – One Day Fecal Immunochemical Test, K170548 | Predicate
InSure FIT Fecal Immunochemical Test, K002457 |
| | | screening for colorectal cancer or other sources of lower g.i. bleeding. |
| Sample Type | Feces | Same |
| Test Principle | Qualitative test system intended for immunochemical detection of fecal occult blood in feces. | Same |
| Detection Method | Lateral flow chromatographic immunoassay | Same |
| Assay Cut-off | 50 μg hemoglobin/g stool | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device
InSure ONE – One Day Fecal Immunochemical Test, K170548 | Predicate
InSure Fecal Immunochemical Test, K002457 |
| Sample Collection | Patient collects and transfers two samples of toilet bowl water from one bowel movement to the test card. | Patient collects and transfers two samples of toilet bowl water from two different bowel movements to the test card. |

## K. Standard/Guidance Document Referenced (if applicable):

CLSI EP12-A2 User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline- Second Edition, 2008.

## L. Test Principle:

The InSure ONE Test uses the principle of immunochromatography to detect human hemoglobin in samples of toilet bowl water collected from around the stool after defecation. The test result is obtained from one stool sample. The toilet bowl water is collected after brushing the surface of the stool to release any blood into the surrounding water. Long handled brushes are used to collect and transfer two samples of toilet bowl water from one bowel movement to the InSure ONE Test Card. The InSure ONE Test Card is used to transport the dried sample to the testing site. At the testing site, an immunochromatographic Test Strip is inserted into the Test Card and Run Buffer is added to rehydrate the sample and to extract the hemoglobin, if present, from the sample. The sample flows along the InSure ONE Test Strip, rehydrates the colloidal gold anti-human hemoglobin conjugate and, if hemoglobin is present, forms a hemoglobin-conjugate immune complex. The complex is then captured on the Test Strip, in a zone containing immobilized anti-human hemoglobin antibodies, to form a visible test line – a positive test. No test line is indicative of the absence of human hemoglobin in the sample – a negative test. Unbound conjugate continues to migrate along the InSure ONE Test Strip and binds to the control line, which contains conjugate-specific antibodies. The control line confirms that the reagent flow is complete and the test is functional.

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# M. Performance Characteristics:

## 1. Analytical performance:

a. Precision/Reproducibility:

Please refer to K002457.

b. Linearity/assay reportable range:

Please refer to K002457.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

### Internal Control

Procedural controls are included in the test device. It confirms sufficient specimen volume and correct procedural technique.

### External Controls

It is recommended that positive and negative controls be performed to verify proper test performance. External controls are not provided with the test kit.

d. Detection limit:

Not applicable

e. Analytical specificity:

Please refer to K002457.

f. Assay cut-off:

Fecal test samples were prepared by spiking stool samples with human blood of known hemoglobin concentration, to obtain the following fecal hemoglobin concentrations: 0 µg Hb/g stool, 5 µg Hb/g stool, 10 µg Hb/g stool, 20 µg Hb/g stool, 30 µg Hb/g stool, 40 µg Hb/g stool, 50 µg Hb/g stool, 60 µg Hb/g stool and 80 µg Hb/g stool. Pre-measured quantities of stool spiked with different levels of hemoglobin were placed in a pre-measured volume of water to simulate toilet water in which stool will be deposited. Following deposition of the stool, water samples were taken at 2 minutes with the InSure sample collection brushes and applied to Test Cards using the InSure FIT and the InSure ONE sampling procedures. Testing was performed side-by-side with the predicate by comparing the test results of the device with that of the predicate. Test Cards were prepared on Day 0, stored at room temperature (20–25°C) and developed on Day 5 to simulate the time span between the patient collecting the fecal water sample on the Test Card and transporting the sampled Test Card to the laboratory by mail. The cut-off was determined to be 50 µg hemoglobin/g stool.

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Table 1. Assay Cut-off Study

| Hb Concentration (μg Hb/g stool) | N | InSure ONE | | Negative Percent Agreement (95% CI) | Positive Percent Agreement (95% CI) |
| --- | --- | --- | --- | --- | --- |
| | | Negative | Positive | | |
| 0 | 40 | 40 | 0 | 100% (91.2% – 100%) | 0% (0% – 8.8%) |
| 5 | 40 | 38 | 2 | 95.0% (83.5% – 98.6%) | 5.0% (1.4% – 16.5%) |
| 10 | 40 | 31 | 9 | 77.5% (62.5% – 87.7%) | 22.5% (12.3% – 37.5%) |
| 20 | 40 | 19 | 21 | 47.5% (32.9% – 62.5%) | 52.5% (37.5% – 67.1%) |
| 30 | 40 | 8 | 32 | 20.0% (10.5% – 34.8%) | 80.0% (65.2% – 89.5%) |
| 40 | 40 | 3 | 37 | 7.5% (2.6% – 19.9%) | 92.5% (80.1% – 97.4%) |
| 50 | 40 | 1 | 39 | 2.5% (0.4% – 12.9%) | 97.5% (87.1% – 99.6%) |
| 60 | 40 | 1 | 39 | 2.5% (0.4% – 12.9%) | 97.5% (87.1% – 99.6%) |
| 80 | 40 | 0 | 40 | 0% (0% – 8.8%) | 100% (91.2% – 100%) |

# 2. Comparison studies:

# a. Method comparison with predicate device:

A method comparison between the InSure ONE and the predicate test-InSure FIT, was conducted to determine if there was a significant difference in test performance between sampling two separate fecal samples once each or a single fecal sample, sampled twice, for detection of occult blood. Patients were recruited from three intended use sites and the study was performed at one intended use site in Australia. The study included an enriched population of patients with gastrointestinal symptoms or a history of past colorectal disease that were scheduled to have a colonoscopy for any reason:

- Patients in an endoscopy unit at a large public hospital that maintained a database of individuals under surveillance, based on their family history or personal history of colorectal cancer or adenomas.
- Patients from the general population based on referral to colonoscopy from their general practitioners for a prior positive fecal occult blood test or other indication.
- Patients from the general population with GI related conditions (i.e., abdominal pain,

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anemia, constipation, diarrhea, diverticulitis, frank rectal bleeding or other GI symptoms).

A total of 859 patients (ages 20 – 93 years old) collected fecal water samples using the InSure FIT (Test Card A) and InSure ONE (Test Card B and Test Card C) prior to colonoscopy. Tissue samples collected at colonoscopy were histopathologically examined for the type of lesion (i.e., cancer, advanced adenoma, etc.). Statistical analysis of the test results for clinical positive percent agreement (PPA) and clinical negative percent agreement (NPA) showed that the InSure ONE test results have acceptable overall agreement with the InSure FIT test results. The study demonstrated that there were no statistically significant differences in the test results obtained from two fecal water sample aliquots taken from one bowel movement (new sampling method with InSure ONE), when compared to one fecal water sample aliquot taken from two separate bowel movements (predicate sampling method with InSure FIT).

Table 2. Patients with Colonoscopy

| Colonoscopy | N | % |
| --- | --- | --- |
| Colonoscopy Completed-Diagnosis Available | 957 | 100 |
| Colonoscopy and InSure FIT Results Available | 895 | 93.5 |
| Colonoscopy, InSure FIT Results & Histopathology Reports Available | 859 | 89.8 |

Table 3. Patients with Colonoscopy and Histopathologic Diagnoses

| Most Advanced Diagnosis (Colonoscopy & Histopathology) | N | % |
| --- | --- | --- |
| Colorectal cancer | 12 | 1.4 |
| Advanced adenoma* | 61 | 7.1 |
| Non-advanced adenoma | 111 | 12.9 |
| Inflammatory bowel disease | 27 | 3.1 |
| Hemorrhoids | 123 | 14.3 |
| Diverticular disease | 158 | 18.4 |
| Hyperplastic polyp | 38 | 4.4 |
| Other GI finding | 35 | 4.1 |
| True Normal | 294 | 34.2 |
| Total | 859 | 100 |

*≥10mm or high grade dysplasia or >2 adenomas or villous component or serrated phenotype.

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Table 4. Summary of Agreement Between Test Card A and Test Card B

| InSure FIT Test Card A | | InSure ONE Test Card B | | | Overall Percent Agreement | Positive Percent Agreement (95% CI) | Negative Percent Agreement (95% CI) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Agreement | Test Card A | Positive | Negative | Total | | | |
| Overall | Positive | 79 | 51 | 130 | 88.7% (86.4 – 90.6%) | 63.2% (54.5 – 71.1%) | 93.1% (91.0 – 94.7%) |
| | Negative | 46 | 683 | 729 | | | |
| | Total | 125 | 734 | 859 | | | |
| Cancer | Positive | 10 | 0 | 10 | 100.0% (75.8 – 100%) | 100.0% (72.2 – 100%) | 100.0% (34.2 – 100%) |
| | Negative | 0 | 2 | 2 | | | |
| | Total | 10 | 2 | 12 | | | |
| Advanced Adenoma | Positive | 12 | 7 | 19 | 80.6% (69.6 – 88.3%) | 63.2% (41.0 – 80.9%) | 87.5% (75.3 – 94.1%) |
| | Negative | 6 | 42 | 48 | | | |
| | Total | 18 | 49 | 67 | | | |
| Non-Advanced Adenoma | Positive | 10 | 8 | 18 | 83.8% (75.6 – 89.6%) | 55.6% (33.7 – 75.4%) | 89.7% (81.5 – 94.5%) |
| | Negative | 9 | 78 | 87 | | | |
| | Total | 19 | 86 | 105 | | | |
| Negative, Non-neoplastic | Positive | 31 | 22 | 53 | 89.2% (85.7 – 92.0%) | 58.5% (45.1 – 70.7%) | 94.2% (91.1 – 96.3%) |
| | Negative | 19 | 309 | 328 | | | |
| | Total | 50 | 331 | 381 | | | |
| Negative, no findings on colonoscopy | Positive | 17 | 13 | 30 | 90.8% (87.0 – 93.6%) | 56.7% (39.2 – 72.6%) | 94.7% (91.3 – 96.8%) |
| | Negative | 14 | 250 | 264 | | | |
| | Total | 31 | 263 | 294 | | | |
| 1 or 2 Non-Advanced Adenoma < 5 mm | Positive | 1 | 4 | 5 | 78.2% (65.6 – 87.1%) | 20.0% (3.6 – 62.4%) | 84.0% (71.5 – 91.7%) |
| | Negative | 8 | 42 | 50 | | | |
| | Total | 9 | 46 | 55 | | | |
| 1 or 2 Non-Advanced Adenoma > 5 mm < 10mm | Positive | 9 | 4 | 13 | 90.0% (78.6 – 95.7%) | 69.2% (42.4 – 87.3%) | 97.3% (86.2 – 99.5%) |
| | Negative | 1 | 36 | 37 | | | |
| | Total | 10 | 40 | 50 | | | |

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Table 5. Summary of Agreement Between Test Card A and Test Card C

| InSure FIT Test Card A | | InSure ONE Test Card C | | | Overall Percent Agreement | Positive Percent Agreement (95% CI) | Negative Percent Agreement (95% CI) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Agreement | Test Card A | Positive | Negative | Total | | | |
| Overall | Positive | 75 | 55 | 130 | 89.2% (86.9 – 91.1%) | 62.0% (53.1 – 70.1%) | 93.6% (91.6 – 95.2%) |
| | Negative | 38 | 691 | 729 | | | |
| | Total | 121 | 738 | 859 | | | |
| Cancer | Positive | 10 | 0 | 10 | 100.0% (75.8 – 100%) | 100.0% (72.2 – 100%) | 100.0% (34.2 – 100%) |
| | Negative | 0 | 2 | 2 | | | |
| | Total | 10 | 2 | 12 | | | |
| Advanced Adenoma | Positive | 12 | 7 | 19 | 80.6% (69.6 – 88.3%) | 63.2% (41.0 – 80.9%) | 87.5% (75.3 – 94.1%) |
| | Negative | 6 | 42 | 48 | | | |
| | Total | 18 | 49 | 67 | | | |
| Non-Advanced Adenoma | Positive | 10 | 8 | 18 | 87.6% (80.0 – 92.6%) | 55.6% (33.7 – 75.4%) | 94.3% (87.2 – 97.5%) |
| | Negative | 5 | 82 | 87 | | | |
| | Total | 15 | 90 | 105 | | | |
| Negative, Non-neoplastic | Positive | 30 | 23 | 53 | 89.5% (86.0 – 92.2%) | 56.6% (43.3 – 69.0%) | 94.8% (91.9 – 96.7%) |
| | Negative | 17 | 311 | 328 | | | |
| | Total | 47 | 334 | 381 | | | |
| Negative, no findings on colonoscopy | Positive | 12 | 18 | 30 | 91.2% (87.4 – 93.9%) | 40.0% (24.6 – 57.7%) | 97.0% (94.1 – 98.5%) |
| | Negative | 8 | 256 | 264 | | | |
| | Total | 20 | 274 | 294 | | | |
| 1 or 2 Non-Advanced Adenoma < 5 mm | Positive | 1 | 4 | 5 | 83.6% (81.7 – 91.1%) | 20.0% (3.6 – 62.4%) | 90.0% (78.6 – 95.7%) |
| | Negative | 5 | 45 | 50 | | | |
| | Total | 6 | 49 | 55 | | | |
| 1 or 2 Non-Advanced Adenoma > 5 mm < 10mm | Positive | 9 | 4 | 13 | 92.0% (81.2 – 96.8%) | 69.2% (42.4 – 87.3%) | 100% (90.6 – 100%) |
| | Negative | 0 | 37 | 37 | | | |
| | Total | 9 | 41 | 50 | | | |

b. Matrix comparison:

Not applicable

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable

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b. Clinical specificity:
Not applicable

c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
Not applicable

N. Instrument Name:
Not applicable

O. System Descriptions:

1. Modes of Operation:
Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device?
Yes _______ or No __x__

Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission?
Yes _______ or No __x__

2. Software:
FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:
Yes _______ or No __x__

3. Specimen Identification:
Enter patient identification information manually on the label of the Test Card.

4. Specimen Sampling and Handling:

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Two separate applications of the fecal water sample, taken from the same bowel movement using a new sample collection brush for each sample. The first fecal water sample is applied to window “1” and the second fecal water sample from the same bowel movement is applied to window “2” on the same Test Card. The sample flap is then sealed with the peel off label. The patient provides their name, date of birth and date the sample was collected on the label included in the instructions for use. The test sample is placed in Test Card in the envelope provided and returned to the laboratory or medical professional office either by mail or personal delivery.

5. Calibration:

Not applicable

6. Quality Control:

Internal Controls: Procedural controls are included in the test device. A pink line appearing the control region is considered as the internal procedural control. The internal procedural control confirms the following: the conjugate was properly hydrated and has flowed through the test and control line areas, the control line antibodies were immunoreactive, and the conjugate is intact. The test is invalid if the control line does not appear.

External Control: It is recommended that positive and negative controls be performed to verify proper test performance. The Enterix Insure FIT FOBT Controls (positive and negative) cleared in K101831, are recommended for use as external controls.

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:

Q. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

R. Conclusion:

The submitted information in this premarket notification is complete and supports substantial equivalence decision.