OC-Auto SENSOR io iFOB Test
Device Facts
| Record ID | K191147 |
|---|---|
| Device Name | OC-Auto SENSOR io iFOB Test |
| Applicant | Eiken Chemical Co., Ltd. |
| Product Code | OOX · Hematology |
| Decision Date | Jan 2, 2020 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 864.6550 |
| Device Class | Class 2 |
Intended Use
OC-Auto Sensor io iFOB Test is designed to be used together as an immunoassay test system. The test system is intended for the qualitative detection of fecal occult blood in feces by professional laboratories. The automated test is used for the measurement of fecal occult blood and is useful as an aid to detect blood in stool when lower gastrointestinal bleeding may be suspected.
Device Story
The OC-Auto Sensor io iFOB Test is an automated immunoassay system for detecting human hemoglobin (hHb) in fecal samples. Patients collect stool samples into specialized bottles containing extraction buffer; bottles are barcoded for automated identification. The system uses latex turbidimetry: anti-human HbA0 antibodies sensitized to polystyrene latex particles react with hHb in the sample, causing agglutination. The analyzer measures optical absorbance changes as light passes through the reaction liquid; absorbance increases proportionally to hHb concentration. The system is operated by professional laboratory staff via an icon-based interface. Results aid clinicians in identifying lower gastrointestinal bleeding. The device provides qualitative results, with 'OR' (over range) or 'PR' (prozone range) flags for concentrations exceeding 1,000 ng/mL. The system includes an automated analyzer, reagents, and controls to ensure measurement accuracy.
Clinical Evidence
No clinical trials were required. Substantial equivalence was established through analytical performance studies and method comparison. Precision/reproducibility studies (n=840 per concentration) showed high agreement (PPA/NPA ≥ 99.8%). Method comparison against the predicate using 405 patient samples and 20 confirmed colorectal cancer cases demonstrated 100% PPA and 100% NPA. Interference testing confirmed no significant impact from animal hemoglobins, meat extracts, vegetable extracts, or common toilet cleaners/supplements.
Technological Characteristics
System uses latex turbidimetry with anti-human HbA0 antibodies on polystyrene latex particles. Analyzer measures optical absorbance changes. Dimensions: 360x560x425 mm; Weight: 35 kg. Power: AC100-240V. Connectivity: Barcode reader for specimen ID; no wireless transmission. Software: NORTi Ver.4.0. Calibration: 5-point curve. Traceable to WHO International Standard (NIBSC 98/708).
Indications for Use
Indicated for the qualitative detection of fecal occult blood in feces by professional laboratories as an aid to detect blood in stool when lower gastrointestinal bleeding may be suspected.
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
- Oc-sensor Diana Ifob Test (K092330)
Related Devices
- K200754 — Hemosure Accu-Reader A100 · W.H.P.M., Inc. · Jun 2, 2022
Submission Summary (Full Text)
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Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY AND INSTRUMENT
I Background Information:
A 510(k) Number
K191147
B Applicant
Eiken Chemical Co., Ltd.
C Proprietary and Established Names
OC-Auto SENSOR io iFOB Test
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| OOX | Class II | 21 CFR 864.6550 - Occult Blood Test | HE - Hematology |
II Submission/Device Overview:
A Purpose for Submission:
Clearance of a new device
B Measurand:
Human hemoglobin (hHb) in feces
C Type of Test:
Qualitative assay
III Intended Use/Indications for Use:
A Intended Use(s):
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"OC-Auto Sensor io iFOB Test" is designed to be used together as an immunoassay test system. The test system is intended for the qualitative detection of fecal occult blood in feces by professional laboratories. The automated test is used for the measurement of fecal occult blood and is useful as an aid to detect blood in stool when lower gastrointestinal bleeding may be suspected.
## B Indication(s) for Use:
Same as Intended Use
## C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
## D Special Instrument Requirements:
Not applicable
## IV Device/System Characteristics:
## A Device Description:
The OC-Auto Sensor io iFOB Test is intended for the qualitative detection of fecal occult blood in feces. The test system is comprised of an automated analyzer, reagents, and sample collection bottles. Specific information regarding each component is provided below:
- OC-Auto Sensor io iFOB Test System analyzer: The analyzer measures optical change. The absorbance increases in proportion to HbA0 concentration in the sample due to latex agglutination as a result of antigen-antibody (latex labeled) reaction. The analyzer determines the calibration curve from calibrators of known concentrations and measures HbA0 in the sample based on the calibration curve. The analyzer can be operated by selecting the icons displayed on the operation panel, following the instruction manual. The analyzer contains following components: OC-sensor io main body, power cord, purified water bottle, wash solution bottle, substitute wash solution bottle, substitute buffer bottle, drain tank, sample rack, paper, drain tube, elbow, L-joint, fuse, instruction manual, and rack bar code label.
- Latex reagent: The Latex Reagent contains polystyrene latex particles sensitized with polyclonal antibodies to human hemoglobin (i.e. anti-human HbA0 antibodies). One vial contains 7 mL of reagent.
- Diluent buffer: One vial contains 200 mL of buffer with 2.38 g of HEPES (N-2-Hydroxyethylpiperazine-N'-2-ethanesulfonic acid).
- Wash concentrate: Aqueous detergent capable of dissolving protein deposits within the fluid path during the cleaning routine. The wash concentrate contains 120 mL of a concentrated wash and each 15 mL is diluted to 500 mL prior to use. The final wash solution concentration contains less than 5% sodium hypochlorite.
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- Calibrator: Contains 3 mL of 1,000 ng/mL purified hemoglobin (i.e. HbA0 derived from human blood) in buffer. The Calibrator is serially diluted prior to analysis with diluent buffer to construct a calibration curve.
- Positive control: Contains 5 mL of purified hemoglobin (i.e. HbA0 derived from human blood) targeted around 150 ng/mL (LV1) and 450 ng/mL (LV2) in buffer.
- Negative control: Contains 1 mL of buffer.
- Sampling bottle: Plastic bottle for collecting fecal sample which contains 2 mL of extraction buffer.
## B Principle of Operation:
The principle of measurement employed for the reagent system is latex agglutination. A latex agglutination reaction is the clumping of antigen- or antibody-sensitized polystyrene latex particles through an antigen-antibody reaction. When anti-human hemoglobin A0 (HbA0) antibody is attached to the polystyrene latex particle and the prepared latex is added to the sample in the cell and agitated, the antigen-antibody reaction starts, and the particle begins to agglutinate. If this agglutination is measured as optical change, the absorbance increases in proportion to HbA0 concentration in the sample. A light beam passes through the reaction liquid to measure changes in the intensity of the transmitted light beam (latex turbidimetry), and changes in the intensity of the scattered light beam (latex nephelometry). Latex turbidimetry is used to measure the amount of an antigen or an antibody by measuring changes in scattered light rays in latex agglutination.
## C Instrument Description Information:
| Modes of Operation | Yes | No |
| --- | --- | --- |
| Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? | ☑ | ☐ |
| Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? | ☐ | ☑ |
| Software | | |
| FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types. | ☑ | ☐ |
1. Instrument Name:
OC-Auto Sensor io iFOB Test
2. Specimen Identification:
The feces samples are collected into the sampling bottles, each of which includes a barcode. When analyzing, the barcode reader in the equipment automatically reads the sampling bottle barcode.
3. Specimen Sampling and Handling:
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Patients collect feces from the sample collection paper or from specimen caught in a clean cup. Contamination from toilet water should be avoided. The collection steps include:
(1) Fill in all required information on the sampling bottle. Open green cap by turning to the left and pulling upwards.
(2) Randomly scrape the surface of the fecal sample with the sample probe. Cover the grooved portion of the sample probe completely with stool sample.
(3) Close sampling bottle by inserting the sample probe and screwing cap on tightly to the right. The sampling bottle contains 2 mL of extraction buffer. Do not reopen. Return the sample device to doctor or laboratory in mailing envelope.
4. Calibration:
Calibration can be operated both automatically or manually by the operator. A new calibration curve must be created under the following conditions: (1) a new lot of latex reagent (2) the value of OC-Control is not within the indicated range (3) opened latex reagent is left onboard for more than seven days (4) after maintenance.
5. Quality Control:
Positive Control: Contains 5 mL of purified hemoglobin targeted around 150 ng/mL in buffer. This product utilizes human hemoglobin which is derived from human blood. The blood is tested for HBs antigens and HIV (HIV-1 and HIV-2) antibodies, and only blood that tests negative is used. Other viruses or pathogens were not tested and may be present. Therefore, when using these reagents, handle them with the same degree of caution as patient samples.
Negative Control: Contains 1 mL of buffer.
V Substantial Equivalence Information:
A Predicate Device Name(s):
Oc-sensor Diana Ifob Test
B Predicate 510(k) Number(s):
K092330
C Comparison with Predicate(s):
| | Candidate device | Predicate device |
| --- | --- | --- |
| Device Trade Name | OC-Auto Sensor io iFOB Test (K191147) | OC-Sensor DIANA iFOB Test (K092330) |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | OC-Auto Sensor io iFOB Test is designed to be used together as an immunoassay test system. The test system is intended for the qualitative detection of fecal occult blood in | “OC-Sensor DIANA iFOB Test” is designed to be used together as an immunoassay test system. The test system is intended for the qualitative detection of fecal occult |
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| | feces by professional laboratories. The automated test is used for the measurement of fecal occult blood and is useful as an aid to detect blood in stool when lower gastrointestinal bleeding may be suspected. | blood in feces by professional laboratories. The automated test is used for the determination of gastrointestinal (GI) bleeding, found in a number of gastrointestinal disorders (GI), e.g. colitis, polyps, and colorectal cancer. The OC-Sensor DIANA iFOB Test is recommended for use in: 1. Routine physical examinations 2. Monitoring bleeding in patients 3. Screening for colorectal cancer or gastrointestinal bleeding |
| --- | --- | --- |
| Sample type | Feces in an extraction buffer | Same |
| Test principle | Measurement of hemoglobin antibody-antigen reaction by latex turbidimetry. | Same |
| Assay cutoff | 20 µg hHb/g stool (100 ng hHb/mL buffer) | 100 ng/mL hHb in fecal extraction buffer |
| Latex reagent | Anti-human HbA0 antibodies sensitized to polystyrene latex particles | Anti-human HbA0 antibodies sensitized to polystyrene latex particles |
| **General Device Characteristic Differences** | | |
| **Analyzer** | | |
| Dimension | W360 x D560 x H425 (mm) | W630 x D560 x H560 (mm) |
| Weight | 35 kg | 60 kg |
| Power required | AC100-240V, 150 VA | AC100-240V, 500VA |
| Operating system | NORTi Ver.4.0 | Windows XP Embedded Adv. |
| Through-put | 88 samples/hour | 280 samples/hour |
| Sample rack | 20 samples: 5 samples × 4 racks | 150 samples: 10 samples × 15 |
| Reaction cuvette | Disposable acrylic cuvette (10 serial cell cuvette) | Semi-disposable acrylic cuvette (11 serial cells × 5 cuvettes) |
| Cell cleaning units | Not included | Included |
| Latex reagent bottle volume | 7 mL | 15 mL |
| Calibrator concentration (top) | 1000 ng Hb/mL | 2000 ng Hb/mL |
| Calibration points | 5 points | 6 points |
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K191147 - Page 6 of 13
| Hemoglobin concentration of calibration points | 0, 50, 200, 500, 1000 ng/mL | 0, 62.5, 125, 250, 500, 1000 ng/mL |
| --- | --- | --- |
VI Standards/Guidance Documents Referenced:
CLSI EP05-A2; Evaluation of Precision Performance of Qualitative Measurement Methods; Approved Guideline - Third Edition.
CLSI EP06-A; Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.
CLSI EP07-A2; Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition.
CLSI EP17-A2; Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition.
CLSI EP25-A; Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline.
VII Performance Characteristics (if/when applicable):
Not applicable
A Analytical Performance:
1. Precision (Repeatability/Reproducibility):
The repeatability study was performed at one site (in house) and the reproducibility study was performed at three sites with one U.S. site and two Japanese sites, by 3–6 operators per site. The instrument (one at each site) and reagents (buffer, latex reagent, OC-calibrator, OC-calibrator diluent, negative control, OC-control LV1, LV2, and LV3) were confounded by site. Hemoglobin (Hb) negative human stool samples were spiked with purified hemoglobin to achieve seven Hb concentrations: 0, 50, 80, 100, 120, 450, and 700 ng/mL. Each sample at each site was tested in two runs per day and 21 replicates per run for 20 days. The positive percentage agreement (PPA) and negative percentage agreement (NPA) for each study at each site are summarized below.
Repeatability:
| | Sample concentration (ng/mL) | Observed positive number | Observed negative number | Total number | Positive percentage agreement with 95% CI (%) | Negative percentage agreement with 95% CI (%) |
| --- | --- | --- | --- | --- | --- | --- |
| Repeatability | 0 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 50 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 80 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 100 | 466 | 374 | 840 | N/A | N/A |
| | 120 | 840 | 0 | 840 | 99.8% (99.1%, 99.9%) | N/A |
| | 450 | 840 | 0 | 840 | 100% (99.5%, 100%) | N/A |
| | 700 | 840 | 0 | 840 | 100% (99.5%, 100%) | N/A |
Reproducibility:
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| | Sample concentration (ng/mL) | Observed positive number | Observed negative number | Total number | Positive percentage agreement with 95% CI (%) | Negative percentage agreement with 95% CI (%) |
| --- | --- | --- | --- | --- | --- | --- |
| Site 1 | 0 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 50 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 80 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 100 | 395 | 445 | 840 | N/A | N/A |
| | 120 | 840 | 0 | 840 | 100% (99.5%, 100%) | N/A |
| | 450 | 840 | 0 | 840 | 100% (99.5%, 100%) | N/A |
| | 700 | 840 | 0 | 840 | 100% (99.5%, 100%) | N/A |
| Site 2 | 0 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 50 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 80 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 100 | 395 | 80 | 760 | N/A | N/A |
| | 120 | 839 | 1 | 840 | 99.9% (99.3%, 100%) | N/A |
| | 450 | 840 | 0 | 840 | 100% (99.5%, 100%) | N/A |
| | 700 | 840 | 0 | 840 | 100% (99.5%, 100%) | N/A |
| Site 3 | 0 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 50 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 80 | 0 | 840 | 840 | N/A | 100% (99.5%, 100%) |
| | 100 | 395 | 80 | 760 | N/A | N/A |
| | 120 | 838 | 2 | 840 | 99.8% (99.1%, 99.9%) | N/A |
| | 450 | 840 | 0 | 840 | 100% (99.5%, 100%) | N/A |
| | 700 | 840 | 0 | 840 | 100% (99.5%, 100%) | N/A |
| All sites | 0 | 0 | 2520 | 2520 | N/A | 100% (99.5%, 100%) |
| | 50 | 0 | 2520 | 2520 | N/A | 100% (99.5%, 100%) |
| | 80 | 0 | 2520 | 2520 | N/A | 100% (99.5%, 100%) |
| | 100 | 514 | 2006 | 760 | N/A | N/A |
| | 120 | 2517 | 3 | 2520 | 99.8% (99.7%, 99.9%) | N/A |
| | 450 | 2520 | 0 | 2520 | 100% (99.5%, 100%) | N/A |
| | 700 | 2520 | 0 | 2520 | 100% (99.5%, 100%) | N/A |
2. Linearity:
Not applicable
3. Analytical Specificity/Interference:
Human Hemoglobin Variants
The sensitivity of OC-Auto Sensor io iFOB test to hemoglobin S (HbS), hemoglobin C (HbC), and hemoglobin F (HbF) were determined using one reagent lot with 21 replicates. Spiked stool samples containing seven concentrations of each variant were prepared: 0, 50, 80, 100, 120, 450, and $700\mathrm{ng / mL}$ . Agreement of positive or negative results for each concentration level was $\geq 90\%$ . Such results showed that the OC-Auto Sensor io iFOB test is sensitive to HbS, HbC, and HbF.
Cross-Reactivity
Cross-reactivity of OC-Auto Sensor io iFOB test with non-human hemoglobin was evaluated by using one reagent lot with 21 replicates. Test samples were prepared by spiking Hb-free stool specimens with known levels of human hemoglobin to obtain fecal samples with the following seven hemoglobin concentrations: 0, 50, 80, 100, 120, 450, and $700\mathrm{ng / mL}$ .
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Fecal samples were spiked with 600 µg/mL of the following animal hemoglobins: cow, turkey, fish, horse, pig, rabbit, goat, and sheep. Agreement of positive or negative results for each concentration level was ≥ 90%. No significant interference was observed for the animal hemoglobin listed above.
## Interference
Interference of OC-Auto Sensor io iFOB test with suspected interferents was evaluated by using one reagent lot with 21 replicates. Test samples were prepared by spiking Hb-free stool specimens with known levels of human hemoglobin to obtain fecal samples with the following seven hemoglobin concentrations: 0, 50, 80, 100, 120, 450, and 700 ng/mL.
Fecal samples were spiked to the final concentration of 2.0% of following animal meat extracts: beef, pork, chicken, lamb, and fish. Fecal samples were spiked to the final concentration of 2.5% of rabbit meat extract. Agreement of positive or negative results for each concentration level was ≥ 90%. No significant interference was observed for these animal meat extracts listed above.
Fecal samples were spiked with 2.5% of the following vegetable extracts: broccoli, cantaloupe, horseradish, red radish, and parsnip. Fecal samples were spiked with 3.3% of the following vegetable extracts: cauliflower and turnip. Agreement of positive or negative results for each concentration level was ≥ 90%. No significant interference was observed for these vegetable extracts listed above.
Fecal samples were spiked with following toilet cleaners to the intended final concentrations: Nuriper (10 mg/mL), Lysol Bleach (10 mg/mL), and Blue Enzyme (1.3 mg/mL). Agreement of positive or negative results for each concentration level was ≥ 90%. No significant interference was observed for these toilet cleaners listed above.
Fecal samples were spiked with the following drugs and supplements to the intended final concentrations: iron (3.1 µg/mL), Vitamin C (2 µg/mL), laxative (0.2 µg/mL), glycerol for enema (2 mg/mL), and peroxidase (25 µg/mL). Agreement of positive or negative results for each concentration level was ≥ 90%. No significant interference was observed for these drugs and supplements listed above.
## 4. Assay Reportable Range:
Not applicable
## 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
### Traceability
OC-Auto Sensor io iFOB Test is traceable to the Haemiglobincyanide World Health Organization (WHO) International Standard (NIBSC code: 98/708).
### Inoculated Sample Stability
For the inoculated sample stability studies, native samples were prepared by mixing a Hb-positive sample pool (from two donors) with Hb-free stool sample in sampling buffer to obtain fecal samples with the following seven approximate Hb concentrations: 0, 50, 80, 100, 120, 450, and 700 ng/mL. The samples were then transferred to the sampling bottles for
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testing. The study was performed by four operators using three reagent sets and three lots of sampling bottles with 21 replicates per test. Each reagent set includes different lots of latex reagent, buffer, calibrator, one negative control, and two positive controls.
The inoculated sample stability study at room temperature was conducted at four temperatures (25, 28, 30, and 33°C) over 16 days (tests on days 0, 7, 15, and 16). The samples were determined to be stable for 15 days at room temperature.
The inoculated sample stability study at refrigerated temperature was conducted at four temperatures (1, 4, 8, and 10°C) over 31 days (tests on days 0, 15, 30, and 31). The samples were determined to be stable for 30 days when refrigerated.
The inoculated sample stability study during shipping was conducted at simulated conditions with a series of temperatures and durations (table below) over 16 days (tests on days 0, 8, and 16). The samples were determined to be stable for 15 days under such simulated shipping conditions.
| Temperature (°C) | 33 | 45 | 35 | 30 | 25 |
| --- | --- | --- | --- | --- | --- |
| Duration (day) | 2 | 0.5 | 1 | 1 | 12 |
## Reagent Stability - Latex Reagent, Buffer, and Calibrator
For the reagent stability study, test samples were prepared by spiking Hb-free stool specimens with known levels of human hemoglobin to obtain fecal samples with the following seven Hb concentrations: 0, 50, 80, 100, 120, 450, and 700 ng/mL. The study was performed using three reagent sets with 21 replicates per test. Each reagent set includes different lots of latex reagent, buffer, calibrator, one negative control, and two positive controls.
The closed bottle reagent stability study was conducted at two temperatures (2 and 8°C) over 13 months (tests on months 0, 6, 12, and 13). The reagents were determined to be stable for 12 months at 2–8°C when unopened.
The stability study for latex reagent of open bottle onboard was conducted at 25°C over 8 days (tests on days 0, 4, 7, and 8). The latex reagent was determined to be stable for 7 days at 25°C when left open onboard.
## Calibrator Stability
For calibrator stability study, the calibrator was diluted with five dilution folds: 0, 2, 5, and 20 (target concentrations 1000, 500, 200, and 50 ng/mL). The calibrator stability study was performed using three reagent sets with three replicates per test. Each reagent set includes different lots of latex reagent, buffer, calibrator, one negative control, and two positive controls. The study was conducted at two temperatures (2 and 8°C) over 19 months (tests on months 0, 6, 12, and 13). The calibrators were determined to be stable for 12 months at 2–8°C.
## Control Stability
For control stability study, one negative and two positive controls (approximate Hb concentrations 150 and 450 ng/mL) were tested. The control stability study was performed using three reagent sets with three replicates per test. Each reagent set includes different lots
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of latex reagent, buffer, calibrator, one negative control, and two positive controls. The study was conducted at two temperatures (2 and 8°C) over 12 months (tests on months 0, 6, 12, and 13). The controls were determined to be stable for 12 months at 2–8°C.
## Shelf Life of Sampling Bottle Stability
For the sampling bottle shelf-life stability study, test samples were prepared by spiking Hb-free stool specimens with known levels of human hemoglobin to obtain fecal samples with the following seven Hb concentrations: 0, 50, 80, 100, 120, 450, and 700 ng/mL. The study was performed by four operators using three reagent sets and three lots of sampling bottles with 21 replicates per test. Each reagent set includes different lots of latex reagent, buffer, calibrator, one negative control, and two positive controls. The sampling bottle stability study was conducted at two temperatures (2 and 30°C) over 19 months (tests on months 0, 9, 18, and 19). The sampling bottles were determined to be stable for 18 months at 2–30°C.
## Wash buffer stability
Wash buffer stability was established in submissions K041408 and K092330.
## Value assignment
Value assignment is performed for each new lot of calibrator. The target calibrator concentration is 1000 ng/mL. For each lot of calibrator, three bottles were diluted by dilution buffer with four dilution folds: 0, 2, 5, and 20 (target concentrations 1000, 500, 200, and 50 ng/mL). The values of diluted calibrator samples were measured using three lots of latex reagents and one lot of buffer with five replicates. The concentration of each calibrator sample was calculated by multiplying the measured concentration of the diluted sample and the according dilution factor. The calibrator concentration is determined as the average of all calibrator concentrations. The calibrator will be released if the concentration is 1000 ± 30 ng/mL.
Value assignment is performed for each new lot of positive controls. The target concentrations of the two positive controls are 150 ng/mL (LV1) and 450 ng/mL (LV2). For each lot of controls, the values were measured by using three lots of latex reagents and one lot of buffer with five replicates. The positive controls will be released if the concentrations were 150 ng/mL ± 11 ng/mL (LV1) and 450 ng/mL ± 35 ng/mL (LV2).
6. Detection Limit:
Not applicable
7. Assay Cut-Off:
Not applicable
8. Accuracy (Instrument):
Not applicable
9. Carry-Over:
Not applicable
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B Comparison Studies:
1. Method Comparison with Predicate Device:
Two independent method comparison studies were performed to compare the candidate OC-Auto Sensor io iFOB test to the predicate OC-Sensor DIANA iFOB test.
The first study was conducted by assessing 405 patient samples, 105 of which were positive and 300 of which were negative. The study was performed by 3–4 operators per site at three clinical laboratories: one in the U.S. and two in Japan. Statistical analysis of site-wide test results as well as combined results demonstrated that the analytical performance of the OC-Auto Sensor io iFOB test is substantially equivalent to the predicate device (OC-Sensor DIANA iFOB).
| Study Site | Candidate results | Predicate results | | | PPA (95% CI) | NPA (95% CI) | OPA (95% CI) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Positive | Negative | Total | | | |
| Site 1 | Positive | 50 | 0 | 50 | 100% (92.9%, 100%) | 100% (96.3%, 100%) | 100% (97.5%, 100%) |
| | Negative | 0 | 100 | 100 | | | |
| | Total | 50 | 100 | 150 | | | |
| Site 2 | Positive | 25 | 0 | 25 | 100% (86.7%, 100%) | 100% (96.3%, 100%) | 100% (97.0%, 100%) |
| | Negative | 0 | 100 | 100 | | | |
| | Total | 25 | 100 | 125 | | | |
| Site 3 | Positive | 30 | 0 | 30 | 100% (88.6%, 100%) | 100% (96.3%, 100%) | 100% (97.1%, 100%) |
| | Negative | 0 | 100 | 100 | | | |
| | Total | 30 | 100 | 130 | | | |
| All sites | Positive | 105 | 0 | 105 | 100% (96.5%, 100%) | 100% (98.7%, 100%) | 100% (99.1%, 100%) |
| | Negative | 0 | 300 | 300 | | | |
| | Total | 105 | 300 | 405 | | | |
The second study was conducted by assessing 20 colorectal cancer (CRC) patients. The colorectal cancer was diagnosed by pathological examination of tissue. All stool samples were collected prior to treatment and prior to colonoscopy and/or biopsy to avoid procedure-related bleeding. The cancer stages and location are summarized below.
| Cancer stage | Number of cases |
| --- | --- |
| 0 | 6 |
| I | 4 |
| II | 5 |
| III | 4 |
| IV | 1 |
| All | 20 |
| Cancer Location | Number of cases |
| --- | --- |
| Rectum | 4 |
| Sigmoid colon | 4 |
| Cecum | 5 |
| Ascending colon | 5 |
| Transverse colon | 2 |
| Descending colon | 1 |
| All¹ | 21 |
The study was performed by one operator at one Japanese clinical laboratory. Statistical analysis of all CRC samples and all samples combined demonstrated that the analytical
¹ One patient had cancers in both rectum and sigmoid colon. Each case is counted separately.
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performance of the OC-Auto Sensor io iFOB test is substantially equivalent to the predicate device.
| Study Site | Candidate results | Predicate results | | | PPA (95% CI) | NPA (95% CI) | OPA (95% CI) |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Positive | Negative | Total | | | |
| CRC patients | Positive | 15 | 0 | 15 | 100% (79.6%, 100 %) | 100% (56.6%, 100 %) | 100% (83.9%, 100%) |
| | Negative | 0 | 5 | 5 | | | |
| | Total | 15 | 5 | 20 | | | |
| All samples | Positive | 120 | 0 | 105 | 100% (96.9%, 100 %) | 100% (98.8%, 100 %) | 100% (99.1%, 100%) |
| | Negative | 0 | 305 | 300 | | | |
| | Total | 120 | 305 | 425 | | | |
Matrix Comparison:
Not applicable
C Clinical Studies:
1. Clinical Sensitivity:
Not applicable
2. Clinical Specificity:
Not applicable
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable
D Clinical Cut-Off:
Not applicable
E Expected Values/Reference Range:
Not applicable
F Other Supportive Instrument Performance Characteristics Data:
Prozone effect (Hook effect)
To determine the possible hook effect of OC-Auto Sensor io iFOB test, one hemoglobin negative stool sample was spiked with freeze-dried internal hemoglobin standard to achieve hemoglobin concentration 500,000 ng/mL. This high concentration sample is then diluted to concentrations 975, 1953, 3906, 7813, 15625, 31250, 62500, 125000, and 250000 ng/mL. Each concentration was measured with three reagent lots in three replicates.
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It was determined that OC-Auto Sensor io iFOB test is not susceptible to prozone/hook effect up to a hemoglobin concentration of 1953 ng/mL. “OR” (over range) or “PR” (prozone range) is displayed when the measurement value is above 1,000 ng/mL.
## VIII Proposed Labeling:
The labeling does support the finding of substantial equivalence for this device.
## IX Conclusion:
The submitted information in this premarket notification is complete and does support a substantial equivalence decision.
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