(136 days)
The Instant-view-plus™ Immunochemical Fecal Occult Blood Test is a qualitative immunoassay for detection of Fecal Occult Blood. It is intended for professional and over the counter use.
This device is a Driven Flow™ chromatographic immunoassay consisting of a test strip housed in a plastic cassette.
Here's a breakdown of the acceptance criteria and study information for the Instant-view-plus™ Immunochemical Fecal Occult Blood Test, based on the provided text:
Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the performance demonstrated in the various studies, particularly the precision/reproducibility and method comparison studies. The goal is to show substantial equivalence to predicate devices, meaning the device performs as well as or better than already approved devices.
The tables below compile the key performance metrics provided:
| Performance Metric | Acceptance Criteria (Implied by Predicate/Good Performance) | Reported Device Performance (Instant-view-plus™) |
|---|---|---|
| Precision/Reproducibility | High Positive/Negative Percent Agreement | Repeatability (Combined Lots): - Positive Percent Agreement: 100% (492/492) (99.3%, 100%) - Negative Percent Agreement: 99% (404/408) (97.5%, 99.7%) |
| Reproducibility (Lot Variability): - Lot 1: Pos. 100%, Neg. 98.6% - Lot 2: Pos. 100%, Neg. 97% - Lot 3: Pos. 100%, Neg. 96.4% | ||
| Reproducibility (Day Variability): - Day 1: Pos. 100%, Neg. 95.1% - Day 2: Pos. 100%, Neg. 89% - Day 3: Pos. 100%, Neg. 98.6% - Day 4: Pos. 100%, Neg. 95.4% - Day 5: Pos. 100%, Neg. 96.8% | ||
| Reproducibility (Site Variability): - Site 1: Pos. 100%, Neg. 97.1% - Site 2: Pos. 100%, Neg. 97.4% - Site 3: Pos. 100%, Neg. 96.7% | ||
| Assay Cut-off | Clearly defined sensitivity/specificity around cut-off | 50 ng/ml (human hemoglobin in fecal sample mixed with detection buffer).At 50 ng/ml: Positive % = 55%, Negative % = 45%At 60 ng/ml: Positive % = 100%, Negative % = 0% |
| Method Comparison (vs. Predicate) | Acceptable Overall, Positive, and Negative Percent Agreement | Combined Sites: - Overall Percent Agreement: 97.7% (95.2%, 99.1%)- Positive Percent Agreement: 96.0% (90.2%, 98.9%)- Negative Percent Agreement: 98.5% (95.6%, 99.7%) |
| Prozone Effect | No significant prozone effect | No prozone effect observed up to 500,000 ng/mL |
| Analytical Specificity (Hb variants) | Equivalent recognition of Hb variants | Equivalently recognizes HbA, HbS, and HbC |
| Cross-Reactivity (Animal Hb) | No significant cross-reactivity | No significant cross-reactivity with tested animal hemoglobins (beef, chicken, fish, horse, goat, rabbit, pig, horseradish peroxidase, sheep) |
| Interfering Substances (Vegetables) | No significant interference | No significant interference from tested vegetable extracts (broccoli, cantaloupe, cauliflower, parsnip, red radish, turnip) |
| Interfering Supplements (Iron, Ascorbate) | No significant interference | No significant interference from iron and sodium L-ascorbate |
| Interference from Toilet Water | No significant interference | No significant interference from samples collected in toilet water |
| Stability (Accelerated/Real Time) | Defined shelf-life | stable for 24 months at 8-23°C |
Study Details:
2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
- Precision/Reproducibility (Repeatability): 6 concentrations (0, 25, 50, 55, 500 ng/ml). 50 replicates per concentration (total of 300 tests per lot). Data provenance is in-house by trained laboratory professionals. This implies retrospective testing of prepared samples.
- Precision/Reproducibility (Reproducibility): 9 concentrations (0, 25, 50, 60, 60 [repeated], 500 ng/ml). 14 replicates for each sample and concentration level. Performed across three intended use sites over a minimum of 5 days. This suggests a prospective data collection design using controlled, spiked samples.
- Prozone Effect Study: 7 concentrations (1,000 to 500,000 ng/ml). 20 aliquots of each concentration. Data provenance is in-house. This is retrospective testing of prepared samples.
- Assay Cut-off Study: 7 concentrations (0, 25, 48, 50, 60, 72, 500 ng/ml). 20 aliquots of each concentration. Data provenance is in-house. This is retrospective testing of prepared samples.
- Method Comparison with Predicate Device: 299 patient samples. Performed at three POC testing sites. Data provenance is not explicitly stated beyond "patient samples" and "POC testing sites," but it implies real-world clinical samples, likely prospective or retrospective from those sites.
- Consumer Study: Concentrations were 0, 25, 50, 60, and 500 ng/ml. "Number of Samples" is consistently "20" (represented as "રત" in the table, clearly a transcription error for 20). Data provenance is in-house using spiked samples. This is retrospective testing of prepared samples.
No specific country of origin for the data is mentioned, but the manufacturer is based in Poway, California, USA, making it highly probable the studies were conducted domestically.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)
- For the precision/reproducibility, prozone, assay cut-off, analytical specificity, cross-reactivity, and interference studies, the ground truth was established by preparing fecal samples spiked with known concentrations of human hemoglobin or other controlled substances. Therefore, no human experts were needed to establish the ground truth; it was experimentally determined.
- For the method comparison study, the "predicate test Instant-view™ Fecal Occult Blood Rapid Test" results served as the reference standard (comparative ground truth). The predicate device itself would have undergone its own validation based on established ground truth (e.g., clinical diagnosis or pathology). For this specific study, the experts are the operators at the three POC testing sites, but their qualifications are not specified beyond "two operators at each site."
- For the consumer study, similarly, no human experts established a true "ground truth." The comparison was between the new device and the predicate device on spiked samples.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
- No explicit adjudication method (like 2+1, 3+1 consensus) is described in the provided text for any of the studies involving human interpretation.
- For studies involving spiked samples, the "truth" is the known concentration of hemoglobin or other substances, eliminating the need for adjudication.
- For the method comparison study, the readings of the Instant-view-plus™ were compared directly to the results of the predicate device, not against an expert-adjudicated ground truth.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- No MRMC comparative effectiveness study involving AI assistance is mentioned. This device is a rapid immunochemical assay, not an AI-powered diagnostic imaging tool. Human interpretation is involved in reading the lines on the cassette.
- A "method comparison with predicate device" study was performed, which compared the new device's readings to those of a predicate device. This is a comparison between devices, not between human readers with and without AI assistance.
- A "consumer study" was performed, which likely involved lay users or professional users following instructions, but it was to assess the device's performance, not the improvement of human readers with AI.
6. If a standalone (i.e., algorithm only without human-in-the-loop-performance) was done
- This device is a standalone test kit that provides a visual readout (presence/absence of lines). Its performance is the algorithm's performance, as the "algorithm" is the biochemical reaction and visual indication. There isn't a separate "human-in-the-loop" vs. "standalone algorithm" distinction in the context of this immunochemical test. The studies evaluate the device's performance directly.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- For the precision/reproducibility, prozone, assay cut-off, analytical specificity, cross-reactivity, interfering substances, and stability studies: The ground truth was experimentally determined by preparing Hb-free fecal samples spiked with known, precise concentrations of human hemoglobin, hemoglobin variants, animal hemoglobins, vegetable extracts, or other interfering substances.
- For the method comparison study: The ground truth was the result from the predicate device (Instant-view™ Fecal Occult Blood Rapid Test).
- For the consumer study: The ground truth was again the known concentration of hemoglobin in the spiked samples, used to compare the new device to the predicate.
8. The sample size for the training set
- The provided text describes studies for validation and verification of the device's performance, not the training of an algorithm. Therefore, there is no specific training set identified in the context of machine learning. The "training" for this type of device would involve development and optimization of the immunoassay components, likely using iterative testing, but this is not a formally reported "training set" in the sense of AI.
9. How the ground truth for the training set was established
- As there's no identified "training set" for an algorithm in the provided text, this question is not applicable. The device's "ground truth" during its development would have been established through controlled laboratory experiments, optimizing reagent formulations and design to achieve desired sensitivity and specificity.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and then the word "ADMINISTRATION" in a smaller font size below that.
Alfa Scientific Designs, Inc. Wen Hua Fan RA Specialist 13200 Gregg St Poway, California 92064
February 15, 2018
Re: K173212
Trade/Device Name: Instant-view-plus immunochemical Fecal Occult Blood Test Regulation Number: 21 CFR 864.6550 Regulation Name: Occult blood test Regulatory Class: Class II Product Code: KHE Dated: January 11, 2018 Received: January 16, 2018
Dear Wen Hua Fan:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kelly Oliner -S
For,
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K173212
Device Name
Instant-view-plus™ Immunochemical Fecal Occult Blood Test
Indications for Use (Describe)
The Instant-view-plus™ Immunochemical Fecal Occult Blood Test is a qualitative immunoassay for detection of Fecal Occult Blood. It is intended for professional and over the counter use.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☒ Prescription Use (Part 21 CFR 801 Subpart D) | ☒ Over-The-Counter Use (21 CER 801 Subpart C) |
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510(k) Summary
| Safety and Effectiveness as Required by 21 CFR 807.92 | |
|---|---|
| Date Prepared: | February 8, 2018 |
| Manufacture and Submitter: | Alfa Scientific Designs, Inc.13200 Gregg StreetPoway, CA 92064Telephone (858) 513-3888 x 324Fax: (858) 513-8388Contact Person: Wen Hua Fan, Ph.D.E-mail: wfan@alfascientific.com |
| Device Name: | Trade Name : Instant-view plusTM ImmunochemicalFecal Occult Blood TestCommon Name: Fecal Immunochemical TestClassification Name: Occult Blood TestClassification: Class IIProduct Code: KHE |
| Predicate Device: | K070660 and K021423 |
Device Description: This device is a Driven Flow™ chromatographic immunoassay consisting of a test strip housed in a plastic cassette.
.
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| Similarities | |||
|---|---|---|---|
| Item | DeviceInstant-view-plusTMImmunochemicalFecal Occult BloodTest, K173212 | PredicateInstant-view®FecalOccult Blood (FOB)Self-TestK070660 | PredicateInstant-view™ FecalOccult Blood RapidTestK021423 |
| Intended use | The Instant-view-plus™ImmunochemicalFecal Occult BloodTest is a qualitativeimmunoassay fordetection of FecalOccult Blood. It isintended forprofessional and overthe counter use. | The Instant-view®Fecal Occult Blood(FOB) Rapid Test is aqualitativeimmunoassay for thedetection of FecalOccult Blood by non-professional, layindividuals as an over-the-counter productfor home use.Measurement of FOBis a useful as an aid todetect blood in stoolas found in a numberof gastrointestinaldisorders, e.g.diverticulitis, colitis,polyps, and colorectalcancer. It is intendedfor over-the-counteruse. The Fecal OccultBlood (FOB) RapidTest is a qualitativeimmunoassay for thedetection of FecalOccult Blood by non-professional, layindividuals as an over-the-counter productfor home use.Measurement of FOBis a useful as an aid todetect blood in stoolas found in a numberof gastrointestinaldisorders, e.g.diverticulitis, colitis, | This Fecal OccultBlood (FOB) RapidTest is animmunochemicaldevice intended forthe qualitativedetection of FecalOccult Blood bylaboratories orphysicians' offices.It is useful todetermininggastrointestinal (GI)bleeding found in anumber ofgastrointestinal (GI)disorders, e.g.,diverticulitis, colitis,polyps, andcolorectal cancer.This test isrecommended foruse in 1) routinephysicalexaminations, whenhospital patients arefirst admitted, 2)hospital monitoringfor bleeding inpatients, 3)screening forcolorectal cancer orgastrointestinalbleeding & anysource. |
| Similarities | |||
| Item | DeviceInstant-view-plusTMImmunochemicalFecal Occult BloodTest, K173212 | PredicateInstant-view®FecalOccult Blood (FOB)Self-TestK070660 | PredicateInstant-viewTM FecalOccult Blood RapidTestK021423 |
| polyps, and colorectalcancer. It is intendedfor over-the-counteruse. | |||
| Sample type | Human feces(mixed with detectionbuffer) | Same | Same |
| Assay cut-off | 50 ng/ml (humanhemoglobin in humanfecal sample inextraction buffer) | Same | Same |
Device Characteristics in Comparison with the Predicate Devices:
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| Differences | |||
|---|---|---|---|
| Item | DeviceInstant-view-plus™Immunochemical FecalOccult Blood Test,K173212 | PredicateInstant-view® FecalOccult Blood (FOB)Self-TestK070660 | PredicateInstant-view™Fecal Occult BloodRapid TestK021423 |
| Test principle | Chromatographicimmunoassay usingDriven Flow™Technology | Lateral flowchromatographicimmunoassay | Lateral flowchromatographicimmunoassay |
| Test device | Cassette | Cassette and dip strip | Cassette and dip strip |
| Assay ReadingTime | Between 1-10 minutes | 4-7 minutes | 5-10 minutes |
Test Principle:
This assay is a Driven Flow chromatographic immunoassay. The device consists of one test strip in a plastic cassette. The test strip consists of:
- . A burgundy colored conjugate pad treated with mouse anti-hHb antibodies conjugated with colloidal gold.
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- A strip of nitrocellulose membrane with a Test line (T-line) and a Control line . (C-line). The T-line is coated with anti-hHb antibodies, and the C-line is coated with goat anti-mouse IgG antibodies.
When an adequate volume of test specimen is dispensed into the sample well of the device, the test specimen migrates across the test strip. If the concentration of hHb in the specimen is at or above 50 ng/ml, the T-line appears as a visible burgundy line. The intensity of the T-line may vary according to the concentration of the hHB in the samples. If the concentration of hHb in the specimen is below the detectable level, no T-line develops. The C-line is coated with goat anti-mouse antibody, which binds to the conjugated monoclonal antibody, regardless of the presence of hHb in the sample.
Precision/Reproducibility:
Repeatability was evaluated using three lots of devices, in-house by two trained laboratory professionals. For repeatability Hb-free fecal samples were collected and spiked with human whole blood with known hemoglobin levels to achieve the following six fecal hemoglobin concentrations: 0 ng/ml, 25 ng/ml, 50 ng/ml, 55 ng/ml, and 500 ng/ml. Fifty replicates were performed for each concentration level.
| Positive PercentAgreement(#Positive/#Total)(95% CI) | Negative PercentAgreement(#Negative/#Total)(95% CI) | |
|---|---|---|
| Lot 1 | 100% (164/164)(97.8%, 100%) | 100% (136/136)(97.3%, 100%) |
| Lot 2 | 100% (164/164)(97.8%, 100%) | 97.8% (133/136)(93.7%, 99.5%) |
| Lot 3 | 100% (164/164)(97.8%, 100%) | 99.3% (135/136)(96.0%, 99.9%) |
| CombinedLots | 100% (492/492)(99.3%, 100%) | 99% (404/408)(97.5%, 99.7%) |
Reproducibility was conducted across three intended use sites using three device lots (same three lots at all sites), and three operators (one at each site) over a minimum of 5 days. For reproducibility Hb-free fecal samples were collected and spiked with human whole blood with known hemoglobin levels to achieve the following nine fecal hemoglobin concentrations: 0 ng/ml, 25 ng/ml, 50 ng/ml, 60 ng/ml, 60 ng/ml, and 500 ng/ml. Fourteen replicates were performed for each sample and concentration level. Insure® FITTM FOBT Controls (K101831) Negative and Positive Controls were also tested daily to ensure the validity of the test results.
Reproducibility - Lot Variability
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| Lot | Positive Percent Agreement(#Positive/#Total)(95% CI) | Negative Percent Agreement(#Negative/#Total)(95% CI) |
|---|---|---|
| Lot 1 | 100 % (684/684)(99.5%, 100%) | 98.6% (568/576)(97.3%, 99.4%) |
| Lot 2 | 100 % (684/684)(99.5%, 100%) | 97% (559/576)(95.3%,98.3%) |
| Lot 3 | 100 % (684/684)(99.5%, 100%) | 96.4% (555/576)(94.5%, 97.7%) |
Reproducibility - Day Variability
| Day | Positive Percent Agreement(#Positive/#Total)(95% CI) | Negative Percent Agreement(#Negative/#Total)(95% CI) |
|---|---|---|
| Day 1 | 100% (410/410)(99.1%, 100%) | 95.1% (329/346)(92.3%, 97.1%) |
| Day 2 | 100% (410/410)(99.1%, 100%) | 89% (308/346)(85.2%, 92.1%) |
| Day 3 | 100% (410/410)(99.1%, 100%) | 98.6% (341/346)(96.7%, 99.5%) |
| Day 4 | 100% (410/410)(99.1%, 100%) | 95.4% (330/346)(92.6%, 97.3%) |
| Day 5 | 100% (410/410)(99.1%, 100%) | 96.8% (335/346)(94.4%, 98.4%) |
Reproducibility - Site Variability
| Site | Positive Percent Agreement(#Positive/#Total)(95% CI) | Negative Percent Agreement(#Negative/#Total)(95% CI) |
|---|---|---|
| Site 1 | 100% (684/684)(99.5%, 100%) | 97.1% (559/576)(95.3%, 98.3%) |
| Site 2 | 100% (684/684)(99.5%, 100%) | 97.4% (561/576)(95.7%, 98.5%) |
| Site 3 | 100% (684/684)(99.5%, 100%) | 96.7% (557/576)(94.9%, 98%) |
Prozone Effect Study:
The Prozone effect was evaluated using three device lots, by two operators testing Hbfree stool specimens spiked with human blood of known hemoglobin concentrations so as to obtain fecal test samples with different Hb concentrations: 1,000 ng/ml (1 ug/ml),
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2,000 ng/ml (2 ug/ml), 3,000 ng/ml (3 ug/ml), 4,000 ng/ml (4 ug/ml), 5,000ng/mL (5 ug/ml), 50,000 ng/mL (50 ug/ml), and 500,000 ng/mL (500 ug/ml). Twenty aliquots of each sample concentration were mixed with extraction buffer in the specimen collection tubes and tested in a randomized order. The results show that Instant-view-plus"M Immunochemical Fecal Occult Blood Test was not affected by highly concentrated hemoglobin in specimen, no prozone effect was observed in the above Hb concentrations.
Stability Studies:
Insure® FIT™ FOBT Controls (K101831) Negative and Positive Controls were also tested daily to ensure and confirm the validity of the test results of the stability studies.
-
- Test Kit Stability (Accelerated)
The accelerated stability study was conducted with three lots of Instant-view-plus™ Immunochemical Fecal Occult Blood Test. Hb-free stool specimens were spiked with human blood (of known hemoglobin level) to obtain fecal samples containing six different hemoglobin concentrations: 0 ng/ml, 25 ng/ml, 50 ng/ml, 60 ng/ml, 72 ng/ml, and 500 ng/ml. Each hemoglobin concentration was tested with two devices from each lot. (2) operator tested the three lots stored at following four temperatures: 20°C (68°F), 23°C (73.4°F), 35°C (95°F), and 60°C (140°F) and test results were collected each day for 20 days. The test kit was determined to be stable for 24 months, when stored at the temperatures between 8 - 23°C (46.4 - 73.4°F).
- Test Kit Stability (Accelerated)
-
- Test Kit Stability (Real Time)
The real time stability study was conducted with three lots of Instant-view-plus™ Immunochemical Fecal Occult Blood Test. Hb-free stool specimens were spiked with human blood (of known hemoglobin level) to obtain fecal samples containing six different hemoglobin concentrations: 0 ng/ml, 25 ng/ml, 60 ng/ml, 60 ng/ml, 72 ng/ml, and 500 ng/ml. Each hemoglobin concentration was tested with four devices from each lot. (2) operators tested the three lots stored at room temperature (20 ~ 23°C) for 26 months. The test kit was determined to be stable for at 24 months.
- Test Kit Stability (Real Time)
Analytical specificity:
Insure® FITTM FOBT Controls (K101831) Negative and Positive Controls were also tested daily to ensure the validity of the test results.
Specificity to human hemoglobin variant
The ability of Instant-view-plus™ Immunochemical Fecal Occult Blood Test to detect human hemoglobin variants was determined by testing hemoglobin-A (HbA). hemoglobin-S (HbS) and hemoglobin-C (HbC) by preparing spiked stool samples containing seven different hemoglobin concentrations: 0 ng/ml, 40 ng/ml, 50 ng/ml, 60 ng/ml, 72 ng/ml, and 500 ng/ml. (3) aliquots of each of the seven concentrations (7 HbA, 7 HbS and 7 HbC supernatants) of spiked stool test samples were
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mixed with detection buffer in Instant-view-plus™ Immunochemical Fecal Occult Blood Test collection bottles. Samples were tested in a randomized order. Results showed Instant-view-plus™ Immunochemical Fecal Occult Blood Test equivalently recognizes variants of hemoglobin HbA, HbS and HbC.
Cross-Reactivity
Cross-reactivity of Instant-view-plus™ Immunochemical Fecal Occult Blood Test with animal hemoglobin was evaluated by testing prepared test samples by spiking Hb-free stool specimen with known levels of human Hb solution to obtain fecal samples with seven different Hb concentrations: 0 ng/ml, 40 ng/ml, 50 ng/ml, 60 ng/ml, 72 ng/ml, and 500 ng/ml. Five replicates of spiked hemoglobin-negative stool concentrations listed above were then spiked with the intended level of respective animal hemoglobin such as beef (2000 ug/ml), chicken (500 ug/ml), fish (100 µg/ml), horse (500 ug/ml), goat (500 µg/ml), rabbit (500 µg/ml), pig (500 µg/ml), horseradish peroxidase (20.000 ug/ml), and sheep (100 ug/ml). All samples were tested in a randomized order. Instant-view-plus™ Immunochemical Fecal Occult Blood Test did not show significant cross-reactivity with any of the animal hemoglobins tested.
Interfering Substances
Susceptibility of Instant-view-plus™ Immunochemical Fecal Occult Blood Test to interference from extracts (vegetable) was evaluated by testing (5) replicates of prepared test samples by spiking Hb-free stool specimen with known levels of human Hb solution to obtain fecal samples with seven different Hb concentrations: 0 ng/ml, 40 ng/ml, 48 ng/ml, 50 ng/ml, 60 ng/ml, 72 ng/ml, and 500 ng/ml. The 5 replicates of the spiked hemoglobin-negative stool concentrations listed above were spiked with the intended level of respective vegetable extracts: broccoli extracts (100%), cantaloupe extract (100%), cauliflower extract (100%), parsnip extract (100%), red radish extract (100%), and turnip extract (100%). All samples were mixed with detection buffer in Instant-viewplus™ Immunochemical Fecal Occult Blood Test sample collection bottles and tested in a randomized order. Instant-view-plus™ Immunochemical Fecal Occult Blood Test did not show significant interference from any of the vegetable extracts.
Interfering Supplements
Susceptibility of Instant-view-plus™ Immunochemical Fecal Occult Blood Test to interference from iron and sodium L-ascorbate was evaluated by testing 3 replicates of prepared test samples by spiking Hb-free stool specimen with known levels of human Hb solution to obtain fecal samples with seven different Hb concentrations: 0 ng/ml, 40 ng/ml. 48 ng/ml, 50 ng/ml, 60 ng/ml, 72 ng/ml. The 3 replicates of spiked hemoglobin-negative stool concentrations were spiked with iron (0.5% (w/v), and sodium L-ascorbate (0.5% (w/v). All samples were mixed with detection buffer in Instant-viewplus™ Immunochemical Fecal Occult Blood Test sample collection bottles and tested in a randomized order. Instant-view-plus™ Immunochemical Fecal Occult Blood Test did not show significant interference from iron and sodium L-ascorbate.
Interference from Toilet Water
Susceptibility of Instant-view-plus™ Immunochemical Fecal Occult Blood Test to
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interference from toilet water was evaluated by testing 40 replicates of prepared test samples by spiking Hb-free stool specimen with known levels of human Hb solution to obtain fecal samples with seven different Hb concentrations: 0 ng/ml, 40 ng/ml, 50 ng/ml, 60 ng/ml, 72 ng/ml, and 500 ng/ml. Twenty replicates of spiked hemoglobinnegative stool concentrations were collected without toilet water and 20 replicates of spiked hemoglobin-negative stool concentrations were collected submerged with toilet water. All samples were mixed with detection buffer in Instant-view-plus™ Immunochemical Fecal Occult Blood Test sample collection bottles and tested in a randomized order. Instant-view-plus™ Immunochemical Fecal Occult Blood Test did not show significant interference from samples collected in toilet water.
Assay cut-off:
The cut-off value for the Instant-view plus™ Immunochemical Fecal Occult Blood (FOB) Test was validated in-house. Fecal test samples were prepared by spiking stool samples with human blood of known hemoglobin concentration, to obtain the following fecal hemoglobin concentrations: 0 ng/ml, 25 ng/ml, 48 ng/ml, 60 ng/ml, 60 ng/ml, 72 ng/ml and 500 ng/ml. Twenty aliquots of each of the seven concentrations of spiked stool test samples were tested in randomized order. Testing was performed side-by-side with the predicate by comparing the test results of the device with that of the predicate. The cut-off was determined to be 50 ng/ml (hemoglobin in fecal sample mixed with detection buffer).
| Concentration | N | Instant-view-plus™™plusImmunochemicalFecal Occult BloodTest | Percent Positive | Percent Negative | |
|---|---|---|---|---|---|
| Positive | Negative | ||||
| 0 ng/ml | 20 | 0 | 20 | 0%0% - 15.5% | 100.00%84.5% - 100% |
| 25 ng/ml | 20 | 1 | 19 | 5%0.80% - 19.80% | 95%80.20% - 99.20% |
| 48 ng/ml | 20 | 11 | 9 | 55%39.12% - 70.82 | 45%29.18% - 60.82% |
| 50 ng/ml | 20 | 11 | 9 | 55%39.12% - 70.82 | 45%29.18% - 60.82% |
| 60 ng/ml | 20 | 20 | 0 | 100%84.5% - 100% | 0%0% - 15.5% |
| 72 ng/ml | 20 | 20 | 0 | 100%84.5% - 100% | 0%0% - 15.5% |
| 500 ng/ml | 20 | 20 | 0 | 100%84.5% - 100% | 0%0% - 15.5% |
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Method comparison with predicate device:
A method comparison of Instant-view plus™ Immunochemical Fecal Occult Blood (FOB) Test with the predicate test, Instant-view™ Fecal Occult Blood Rapid Test, was conducted by assessing 299 patient samples. The method comparison study was performed at three POC testing sites by two 2 operators at each site. The Insure® FITTM FOBT Controls (K101831) Negative and Positive Controls were run prior to testing. Statistical analysis of site-wide test results as well as combined results showed that Instant-view plus™ Immunochemical Fecal Occult Blood (FOB) Test results have acceptable overall percent agreement as well as positive percent agreement and negative percent agreement with Instant-view™ Fecal Occult Blood Rapid Test. The method comparison study demonstrated that the analytical performance of the Instant-view plus™ Immunochemical Fecal Occult Blood (FOB) Test is substantially equivalent to the predicate device.
| Study Site | Instant-view-plusTMImmunochemicalFOB Test | Predicate TestInstant-View Fecal OccultBlood Rapid Test | NegativePercentAgreement(95% CI) | Positive PercentAgreement(95% CI) | Overall PercentAgreement(95% CI) | ||
|---|---|---|---|---|---|---|---|
| Positive | Negative | Total | |||||
| Site 1 | Positive | 36 | 1 | 37 | 98.5%(92.1%, 99.9%) | 94.7%(82.3%, 99.4%) | 97.2%(92.0%, 99.4%) |
| Negative | 2 | 67 | 69 | ||||
| Total | 38 | 68 | 106 | ||||
| Site 2 | Positive | 36 | 1 | 37 | 98.9%(93.8%, 99.9%) | 97.3%(85.8%, 99.9%) | 98.4%(94.3%, 99.8%) |
| Negative | 1 | 87 | 88 | ||||
| Total | 37 | 88 | 125 | ||||
| Site 3 | Positive | 25 | 1 | 26 | 97.6%(87.4%, 99.9%) | 96.2%(80.4%, 99.9%) | 97.1%(89.8%, 99.6%) |
| Negative | 1 | 41 | 42 | ||||
| Total | 26 | 42 | 68 | ||||
| CombinedSites | Positive | 97 | 3 | 100 | 98.5%(95.6%, 99.7%) | 6.0%(90.2%, 98.9%) | 97.7%(95.2%, 99.1%) |
| Negative | 4 | 195 | 199 | ||||
| Total | 101 | 198 | 299 |
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Consumer Study:
To support over the counter use, a consumer study was performed by testing Instant-view plus™ Immunochemical Fecal Occult Blood (FOB) Test with the predicate test, Instantview® Fecal Occult Blood (FOB) Self-Test hemoglobin free feces spiked samples at the following concentrations: 0 ng/ml, 25 ng/ml, 50 ng/ml, 60 ng/ml, and 500 ng/ml.
| Concentration | NumberofSamples | Predicate Device | New Device | Difference (New - Predicate) | |||
|---|---|---|---|---|---|---|---|
| (ng/mL) | Negative(%) | Positive(%) | Negative(%) | Positive(%) | Negative %(95% CI ofDifference) | Positive %(95% CI ofDifference) | |
| 0 | રત | રવ | 0 | રવ | 0 | 0(-6.8%,6.8%) | 0(-6.8%,6.8%) |
| 25 | રત | 52 | 2 | રે રે | 1 | 1.9%(-6.8%, 1.1%) | -1.9%(-11.1%, 6.8%) |
| 50 | રત | 25 | 29 | 26 | 28 | 1.9%(-17.4%, 21.0%) | -1.9%(-21.0%, 17.4%) |
| 60 | રત | l | રે રે | l | રે રે | 0(-8.6%, 8.6%) | 0(-8.6%, 8.6%) |
| 500 | રત | 0 | ર્ડવ | 0 | રવ | 0(-6.8%, 6.8%) | 0(-6.8%,6.8%) |
§ 864.6550 Occult blood test.
(a)
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.)(b)
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.