The BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test İs intended for the qualitative determination of cardiac troponin I in human whole blood, plasma or serum. Measurement of troponin I values are useful in the evaluation of acute myocardial infarction (AMI).

Device Description

The BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test is a colloidal gold/antibody conjugatebased immunoassay designed for the detection of cTnl in human whole blood, plasma and serum samples. To perform the BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test, the sample is dispensed into the sample well. The red cells in the whole blood will react with certain biochemical reagents (such as anti-red blood cells) which are immobilized in the sample pad. This reaction will cause the red blood cells to bind to the sample pad, allowing only the plasma to travel forward. CTnl that is present in the specimen is bound by a gold-antibody conjugate forming a gold-antibody-antigen complex. This complex migrates across the membrane by capillary action and reacts with three anticTnl monoclonal antibodies immobilized in the test region to produce a pink color band when the cTnl concentration is equal to or greater than 1.5 ng/ml. If cTnl is not present in the specimen, there is no line in the test line area. The mixture continues to migrate to the procedural control line area and produce a pink color band. If no procedural control line is present, the sample is invalid and should be retested.

AI/ML Overview

This document describes the test performance characteristics of the BioCheck Whole Blood/Plasma/Serum cTnI Rapid Test. Here's a breakdown of the acceptance criteria and study details:

1. Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" as a separate section with predefined targets. Instead, it presents various test performances which implicitly serve as the criteria the device met.

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Precision (Between Runs - Serum)	100% agreement	100% agreement between runs and between four testing sites
Precision (Between Runs - Whole Blood)	100% agreement	100% agreement between runs and between four testing sites
Recovery Study (Serum)	100% agreement	100% agreement between expected and observed results at each cTnI concentration
Recovery Study (Whole Blood)	100% agreement	100% agreement between expected and observed results at each cTnI concentration
Interference (Various analytes & drugs)	No interference up to specified levels	No interference observed at the indicated test levels for all listed analytes and drugs
Clinical Correlation (Serum samples vs. ELISA)	High Sensitivity, Specificity, and Accuracy	Sensitivity = 97.3%, Specificity = 97.1%, Overall Accuracy = 97.1%
Correlation (Whole Blood vs. Plasma)	100% agreement	100% agreement (68/68 samples)
Clinical Studies (Confirmed MI - Whole Blood)	High agreement with patient status	95.8% agreement (23/24 samples) with confirmed MI status
Clinical Studies (Non-MI - Whole Blood)	100% agreement with patient status	100% agreement (44/44 samples) with non-MI status
Correlation (Whole Blood vs. Serum - Spiked Samples)	100% agreement	100% agreement between whole blood and serum spiked samples

2. Sample Size Used for the Test Set and Data Provenance:

Precision (Serum & Whole Blood):
- Each of 4 labs tested 5 blind replicates of 3 different cTnI concentrations (0, 1.5, 3.0 ng/ml).
- Total tests per site = 15. Total over 4 sites = 60. Manufacturer's lab also tested.
- Data Provenance: Not explicitly stated, likely internal to BioCheck Inc. and collaborating labs. Retrospective from spiked samples.
Recovery Study (Serum & Whole Blood):
- 6 replicates for each of 5 cTnI concentrations (0, 0.5, 1.0, 1.5, 3.0 ng/ml).
- Total replicates per sample type = 30. Total for both serum and whole blood = 60.
- Data Provenance: Not explicitly stated, likely internal to BioCheck Inc. Retrospective from spiked samples.
Interference:
- Amount not specified, but various analytes and drugs were tested at specified concentrations.
- Data Provenance: Not explicitly stated, likely internal to BioCheck Inc. Retrospective from spiked samples.
Clinical Correlation (Serum):
- Test Set Size: 245 patient serum samples.
- Data Provenance: Not explicitly stated, but implies patient samples, likely retrospective. Country of origin not specified.
Correlation (Whole Blood vs. Plasma):
- Test Set Size: 68 paired whole blood and plasma samples from patients.
- Data Provenance: Patient samples, likely retrospective. Country of origin not specified.
Clinical Studies (Confirmed MI Patients - Whole Blood):
- Test Set Size: 24 whole blood specimens from confirmed MI patients.
- Data Provenance: Patient samples, likely retrospective. Country of origin not specified.
Clinical Studies (Non-MI Patients - Whole Blood):
- Test Set Size: 44 whole blood specimens from non-MI patients.
- Data Provenance: Patient samples, likely retrospective. Country of origin not specified.
Correlation (Whole Blood vs. Serum - Spiked Samples):
- Test Set Size: 20 individuals provided paired whole blood and serum samples, spiked with cTnI.
- Data Provenance: Not explicitly stated, likely internal to BioCheck Inc. Retrospective from spiked samples.

3. Number of Experts and Qualifications for Ground Truth:

For the Clinical Correlation Study and Clinical Studies (confirmed MI and non-MI patients), the reference method for confirming cTnI levels was a "commercially available quantitative ELISA assay for cTnI" and the "BioCheck cTnI ELISA Test."
For the "Confirmed MI Patients" and "Non-MI Patients" studies, the ground truth refers to "patient status" as confirmed MI or non-MI. This implies clinical diagnosis, likely involving medical professionals, but the number and qualifications of these experts are not specified in the document. The ELISA assay serves as the reference for the cTnI concentration in these studies.

4. Adjudication Method for the Test Set:

The document describes comparisons to existing methods (ELISA for cTnI, clinical status for MI). There is no explicit mention of an adjudication method (e.g., 2+1, 3+1 consensus) for establishing the ground truth or resolving discrepancies in any of the studies. The reference methods are assumed to be definitive.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

No, an MRMC comparative effectiveness study was not done. This device is a rapid diagnostic test for qualitative determination of cTnI, not an AI-assisted diagnostic tool for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable.

6. Standalone Performance:

Yes, standalone performance was done. All the reported performance metrics (precision, recovery, interference, clinical correlation, and clinical studies) assess the performance of the BioCheck Whole Blood/Plasma/Serum cTnI Rapid Test on its own, without human-in-the-loop assistance. It is designed to provide a direct qualitative result.

7. Type of Ground Truth Used:

Expert Consensus / Reference Assay and Clinical Outcomes:
- For assays confirming cTnI levels, the ground truth was established by comparison to a commercially available quantitative ELISA assay for cTnI (implicitly considered a gold standard for cTnI concentration).
- For the "Clinical Studies" on confirmed MI and non-MI patients, the ground truth for patient status was based on clinical diagnosis ("confirmed MI patients" and "non-MI patients"), likely supported by the ELISA results, which falls under clinical outcomes/diagnosis, implicitly representing expert medical consensus.
- For spiked samples, the ground truth was the known, introduced concentration of cTnI.

8. Sample Size for the Training Set:

The document does not mention a training set or indicate that the device used machine learning or AI algorithms requiring a training set. This is a traditional immunoassay. The studies described are validation and performance testing, not model training.

9. How the Ground Truth for the Training Set Was Established:

Not applicable, as there is no mention of a training set for this device.

Summary

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BioCheck, Inc. DEC 17 2004

CARDIAC- 1 RAPID TEST

FOR THE QUALITATIVE DETERMINATION OF CARDIAC TROPONIN I In Human Whole Blood, Plasma or Serum

Catalog No.: 850116

MANUFACTURER: t.

BioCheck, Inc. 323 Vintage Park Drive Foster City, CA 94404 Phone: (650) 573-1968 Fax: (650) 573-1969 Regulatory Contact: Hellen Professional Services Phone: (818) 709-5646

II. DEVICE NAME and CLASSIFICATION:

Proprietary Name:	BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test
Catalog Number:	850116
Common Name:	BioCheck Cardiac-1 Rapid Test
Classification Name:	Creatine Phosphokinase/Creatine Kinase or Isoenzymes Test System (862.1215)

111. INTENDED USE and ASSAY PRINCIPLE:

The BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test is intended for the qualitative determination of cardiac troponin I in human whole blood, plasma or serum. Measurement of troponin I values are useful in the evaluation of acute myocardial infarction (AMI).

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IV. SUBSTANTIAL EQUIVALENCE:

The BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test is a modification of the existing BioCheck Serum Troponin I Rapid Test (formerly, the VBL Serum Troponin I Test, K023505; currently manufactured by BioCheck, Inc., Foster City, CA 94404). The original rapid troponin I test was cleared for use on serum samples, and the new, reformulated device can be used to detect human cTnl in whole blood, plasma or serum specimens. The intended use of the product has not been altered significantly, only expanded to include the use of whole blood and plasma samples.

V. TEST PERFORMANCE:

1. Precision

PRECISION-BETWEEN RUNS AT FOUR DIFFERENT TESTING SITES SERUM . Samples
Four laboratories were provided with blind serum samples that had been spiked with purified complex cTnl *. Three serum samples containing 0. 1.5, and 3.0 ng/ml cTn1 were prepared. Five blind replicates of each sample were tested in each site for a total of 15 tests per site. All samples were also tested in manufacture's laboratory. The assay results demonstrated 100% agreement in between run proficiency and 100% agreement between sites using serum samples.
. PRECISION-BETWEEN RUNS AT FOUR DIFFERENT TESTING SITES - WHOLE BLOOD Samples
Between run precision was evaluated at four different sites. Four laboratories were provided with blind whole blood samples which were spiked with purified complex cTn1. Samples were prepared containing 0 ng, 1.5 ng and 3.0 ng/ml of cTnl. Five blind replicates of each sample were tested at each site for a total of 15 tests per site. All samples were also tested in the manufacturer's laboratory. The assay results demonstrate 100% agreement in between-run proficiency. and 100% agreement between sites using whole blood samples.

2. Recovery Study

Sample recovery was tested using serum samples and whole blood samples with the BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test.

For the serum evaluation, normal human serum was supplemented with partially purfied human cTnl complex to yield cTnl concentrations of 0, 0.5, 1.0, 1.5 and 3.0 ng/ml. The whole blood samples were tested by using normal human whole blood specimens spiked with partially purified human cTnl complex to yield cTnl concentrations of 0, 0.5, 1.0, 1.5 and 3.0 ng/ml.

The spiked samples were tested in six replicates using the BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test. The data showed 100% agreements between the expected and the observed results at each cTnl concentration for both serum and whole blood samples (results shown as # positive results/total # tested).

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V. TEST PERFORMANCE:

3. Interference

The following potentially interfering substances do not appear to interfere with the determination of cTnl in the BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test up to the levels indicated below. Identical results were observed in the serum-only test.

Analyte	Test Level	Analyte	Test Level
Biotin	200 ng/ml	Human muscle Troponin T	2.5 µg/ml
Bilirubin	20 mg/dl	Human muscle Troponin I	2.5 µg/ml
Hemoglobin	1200 mg/dl	Cholesterol	800 mg/dl
Rabbit skeletal muscleTroponin C	2.5 µg/ml	Triglyceride	1250 mg/dl
Human cardiac Troponin T	2.5 µg/ml

In vitro testing of the following common-used drugs revealed no interference at the upper level of the therapeutic range in the BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test. Identical results were observed in the serum-only test.

Analyte	Test Level	Analyte	Test Level
Acetaminophen	30 µg/ml	Digitonin	10 µg/ml
Acetylsalicylic acid	200 µg/ml	Digoxin	10 µg/ml
Adenine	10 µg/ml	Dopamine	10 µg/ml
Albumin (bovine)	50 mg/ml	Erythromycin	20 µg/ml
Allopurinol	20 µg/ml	Gentistic acid	10 µg/ml
Ambroxol	10 µg/ml	Isoproterenol	10 µg/ml
Ampicillin	20 µg/ml	Isosorbide dinitrate	50 µg/ml
Ascorbic acid	20 µg/ml	Nifedipine	200 µg/ml
Atenolol	10 µg/ml	Nystatin	10 µg/ml
Atropine	10 µg/ml	Oxazepam	10 µg/ml
Caffeine	20 µg/ml	Oxytetracycline	10 µg/ml
Captopril	10 µg/ml	Propranolol	10 µg/ml
Chloramphenicol	25 µg/ml	Theophylline	20 µg/ml
Cinnarizine	10 µg/ml	L-thyroxine	10 µg/ml
Cyclophosphamide	125 µg/ml	Urea	400 µg/ml
Cyclosporine	10 µg/ml	Uric acid	100 µg/ml

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4. Clinical Comparison

CLINICAL CORRELATION STUDY .

A total of 245 patient serum samples were tested using the BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test. Results were compared with a commercially available quantitative ELISA assay for cTnl as shown below:

BioCheck Whole Blood /Plasma / Serum cTnlRapid Test	BioCheck, Inc.Troponin I ELISA Test
	≥ 1.5 ng/ml	< 1.5 ng/ml
+	73	5
-	2	165
Total	75	170

Sensitivitv = 73 / 75 = 97.3% Specificity = 165 /170 = 97.1% Overali Accuracy = 238 /245 = 97.1%

CORRELATION STUDY between WHOLE BLOOD and PLASMA Samples . Sixty-eight (68) patient whole blood samples were collected and plasma isolated. The paired samples were tested using the BioCheck Whole Blood/Plasma/Serum cToil Rapid Test. The agreement between the whole blood test and plasma test was 100% (68/68),

V. TEST PERFORMANCE:

t CLINICAL STUDIES - CONFIRMED MI Patients: BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test and BioCheck ELISA Test Twenty-four (24) whole blood specimens from confirmed MI patients were tested with the BioCheck Whole Blood/Plasma/Serum cTn1 Rapid Test and BioCheck cTnJ ELISA..Test. Among these specimens, 23 were found to have positive test results and the agreement with the patient status was found to be 95.8% (23/24).
CLINICAL STUDIES - NON-MI Patients: BioCheck Whole Blood/Plasma/Serum cTn1 . Rapid Test and BioCheck ELISA Test Similarly, whole blood specimens from non-MI patients (n=44) were tested with the BioCheck Whole Blood/Plasma/Serum cTnl Rapid Test and the BioCheck cTnl ELISA Test. Negative results were obtained for both test protocols for all 44 speciments and 100% (44/44) agreement was achieved.
CORRELATION of ASSAY RESULTS BETWEEN WHOLE BLOOD AND SERUM . SAMPLES
A pair of samples, one whole blood (WB) and one serum (S), were collected from each of 20 individuals. The whole blood and serum samples from each individual were spiked with the same amount of purified complex cThil. The samples of 17 individuals were prepared containing ≥ 1.5 ng/ml of cTnl while samples of 3 individuals containing < 1.5 ng/ml of cTnl. The agreement between the use of whole blood and serum was 100%.

CAT. NO. 850116PI

Revision Date: 09-01-04

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Image /page/4/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is an abstract image of an eagle with its wings spread.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 17 2004

Biocheck, Inc. c/o Robin J. Hellen, M.S. Hellen Professional Services 9418 Lasaine Avenue Northridge, CA 91325

Re: K041619

Trade/Device Name: BioCheck, Inc. Whole Blood/ Plasma/ Serum cTnl Rapid Test Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/ creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: MMI Dated: November 8, 2004 Received: November 17, 2004

Dear Ms. Hellen:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) I mis letter will and w you wo ough finding of substantial equivalence of your device to a legally premained notificate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In of quostions on the promie Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Cornelia B. Lorks

Cornelia B. Rooks, MA Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

Device Name:

BioCheck, Inc. Whole Blood/Plasma/Serum cTnl Rapid Test

Indications for Use:

Prescription Use
(Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

に

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Bensam
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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510(k) K041619

Regulation Number and Section

§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.

(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.