CLINITEST HCG PREGNANCY TEST

K032563 · Bayer Healthcare, LLC · JHI · Dec 23, 2003 · Clinical Chemistry

Device Facts

• Record ID: K032563
• Device Name: CLINITEST HCG PREGNANCY TEST
• Applicant: Bayer Healthcare, LLC
• Product Code: JHI · Clinical Chemistry
• Decision Date: Dec 23, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1155
• Device Class: Class 2

Indications for Use

The Bayer Healthcare Clinitest hCG Pregnancy Test is for in vitro diagnostic use as a qualitative method in the rapid detection of human chorionic gonadotropin (hCG) in urine specimens. The test is utilized with the Clinitest Status analyzer and is intended for near patient (point of care) and centralized laboratory locations.

Device Story

Clinitest hCG Pregnancy Test is a qualitative sandwich-type immunochromatographic assay. Input: urine specimen applied to test cassette. Principle: anti-beta hCG antibodies coupled to colloidal gold particles bind hCG in sample; complex migrates to test line containing anti-alpha hCG antibodies, forming visible pink line. Control line uses goat anti-mouse IgG. Device is used with Clinitek Status analyzer; instrument reads reflectance of test line, reference line, and calibration bar. Output: qualitative result (positive, negative, or borderline). Borderline results prompt retest in 48-72 hours. Used in point-of-care or lab settings by professionals. Benefits: automated reading removes subjectivity of visual interpretation, providing standardized results based on 25 mIU/mL cutoff.

Clinical Evidence

No clinical studies performed. Evidence consists of analytical performance data: precision/reproducibility (intra-instrument CV <10% weak, <4% moderate/strong; inter-instrument CV <11% weak, <4.6% strong) and method comparison study (n=3120) against visually read predicate. Agreement analysis showed 99.7% negative agreement and 99.1% positive agreement after resolving discrepancies with RIA.

Technological Characteristics

Qualitative sandwich-type immunoassay; monoclonal anti-alpha hCG antibodies (test line), goat anti-mouse IgG (control line), colloidal gold-labeled anti-beta hCG. Dimensions: test cassette. Connectivity: Clinitek Status analyzer. Calibration: internal self-calibration via white plastic bar and reference line. Standards: ISO 14971, ISO 13485, IEEE 1012, ISO/IEC 12207, AAMI/ANSI SW68, IEC 60601-1-2.

Indications for Use

Indicated for the qualitative detection of human chorionic gonadotropin (hCG) in urine specimens to aid in the detection of pregnancy. Intended for use in near-patient (point-of-care) and centralized laboratory settings using the Clinitek Status analyzer.

Regulatory Classification

Identification

A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.

Predicate Devices

• Clinitest hCG Pregnancy Test (K023944)
• Quidel QuickVue One-Step hCG Combo (K020801)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k032563

B. Analyte:
hCG

C. Type of Test:
Qualitative immunochromatographic test cassette analyzed on the Clinitek Status analyzer

D. Applicant:
Bayer Healthcare, LLC

E. Proprietary and Established Names:
Clinitest hCG Pregnancy Test

F. Regulatory Information:
1. Regulation section:
21 CFR § 862.1155
2. Classification:
Class II
3. Product Code:
JHI
4. Panel:
75 Clinical Chemistry

G. Intended Use:

1. Indication(s) for use:
The Bayer Healthcare Clinitest hCG Pregnancy Test is for in vitro diagnostic use as a qualitative method in the rapid detection of human chorionic gonadotrophin (hCG) in urine specimens. The test is utilized with the Clinitek Status analyzer and is intended for near patient (point of care) and centralized laboratory locations.

2. Special condition for use statement(s):
For professional use only. The assay is intended for use in point-of-care and centralized laboratory settings.

3. Special instrument Requirements:
Clinitek Status Analyzer

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# H. Device Description:

The Clinitest hCG pregnancy Test is a qualitative sandwich-type immunoassay. The test contains monoclonal anti-alpha hCG antibodies in the test line and goat anti-mouse IgG antibodies on the control line. Colloidal gold particles are coated with anti-beta hCG antibodies. The test strip was previously cleared under K023944. This submission is for clearance of the strip to be automatically read on the Clinitek Status analyzer.

# I. Substantial Equivalence Information:

1. Predicate device name(s):
Bayer Clinitest® hCG Pregnancy Test and
Quidel QuickVue® One-Step hCG-Combo
2. Predicate K number(s):
k023944
k020801
3. Comparison with predicate:

The device and its predicates share the same intended use and basic assay principle. Other similarities and differences are outlined below.

| Similarities | | | |
| --- | --- | --- | --- |
| Item | Clinitest® hCG Pregnancy Test (read on analyzer) | Clinitest® hCG Pregnancy Test | Quidel QuickVue® One-Step |
| Sample type | Urine | Urine | Urine or Serum |
| Sample volume | ~200 μL | ~200 μL | ~125 μL |
| Positive Cut-off | 25 mIU/mL | 25 mIU/mL | 25 mIU/mL |
| Differences | | | |
| Item | Clinitest® hCG Pregnancy Test (new use) | Clinitest® hCG Pregnancy Test | Quidel QuickVue® One-Step |
| Result reading | Read by Clinitek Status analyzer | Visually read | Visually read |
| Reagent calibration | WHO 3^{rd} IRP | WHO 3^{rd} IRP | WHO 4^{th} IS (75/589) |
| Time to result | 5 minutes for confirmation of negative | 5 minutes for confirmation of negative | 3 minutes for confirmation of negative |

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

The following standards and guidance documents are referenced in the submission:

- ISO 14971:2000 Medical Devices – Application of Risk Management to Medical Devices

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- ISO 13485:1996 – Quality Systems – Medical Devices – Particular Requirements for the Application of ISO 9001
- IEEE 1012:1998 – Standard for Software Verification and Validation. (Software)
- ISO/IEC 12207:1995 – Information technology – Software Life Cycle Processes
- AAMI/ANSI SW68:2001 – Medical device software – Software Life Cycle Processes Capability - Maturity Model version 1.3
- IEC (EN) 60601-1-2:1993 (Second edition, 2001), Medical Electrical Equipment – Part 1: General Requirements for Safety; Electromagnetic Compatibility – Requirements and Tests
- Recognition and Use of Consensus Standards, Final Guidance for Industry and FDA Staff
- The Least Burdensome Provision of the FDA Modernization Act of 1997: Concepts and Principles; Final guidance for Industry and FDA
- Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices
- Review Criteria for Assessment of Professional Use Human Chorionic Gonadotropin (hCG) In Vitro Diagnostic Devices (IVDs)

## K. Test Principle:

The Clinitest hCG test strips were cleared under k023944. Sample introduced into the sample well reacts with anti-beta hCG antibodies coupled to colloidal gold particles. This mixture moves chromatographically up the test strip. If there is hCG in the sample, the hCG/colloidal gold will bind the anti-alpha hCG antibodies on the test line thus forming a pink colored line. There is also a control line of goat anti-mouse antibodies to control for chromatographic flow in the cassette.

For automatic reading on the Clinitek analyzer, the cassette is placed in the analyzer immediately following sample application. The instrument reads the reflectance and compares the intensity to that of a reference line that has been adjusted to reflect a level of approximately $25\mathrm{mIU/mL}$ hCG.

## L. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Evaluations of intra- and inter-instrument precision were made using immuno hard standards, which consist of 5 printed lines whose width and reflectance spectra are similar to that of the Clinitest strips. Ten (10) different standards were randomly read on 52 instruments with and 10 measurements of a single cassette on two single instruments. Data was generated for lines designated as blank, weak, moderately intense, or strong. The intra-instrument $\%$ CV was reported as $&lt;10\%$ for weak lines, and $&lt;4\%$ for moderate and strong lines. Inter-instrument $\%$ CV was reported as $&lt;11\%$ for weak lines, and $&lt;4.4\%$ for moderate lines, and $&lt;4.6\%$ for strong lines. Day-to-day precision was evaluated in a similar manner over a 27-week period. The resulting $\%$ CVs were consistent with intra- and inter-instrument precision results.

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# b. Linearity/assay reportable range:

Not applicable. The assay is intended for qualitative use.

# c. Traceability (controls, calibrators, or method):

The instrument is designed to self-calibrate prior to every cassette measurement. Reflectance readings are taken at the white plastic calibration bar, at the reference line (designed to represent approximately $25\mathrm{mIU / mL}$ hCG concentration), at the test line, and at the control line. From those readings, the machine can compare the test line to the reference line (as corrected by the dark current reading and the calibration bar) to determine whether the hCG level is $\geq$ the intensity of a line with $25\mathrm{mIU / mL}$ .

The device has an internal process control.

# d. Detection limit:

See assay cut-off below for qualitative cut-off levels. The positive cutoff was validated with the clearance of the cassette.

Negative urine samples spiked with hCG were tested on the Clinitek analyzer using the Clinitest strips. The following instrument results were obtained (n=36 at each concentration of hCG):

| hCG (mIU/mL) | Percent Positive |
| --- | --- |
| 0 | 0 |
| 2 | 0 |
| 5 | 0 |
| 10 | 0 |
| 15 | 16.6 |
| 20 | 72.2 |
| 25 | 100 |
| 50 | 100 |
| 100 | 100 |

# e. Analytical specificity:

The test strips read by the Clinitek analyzer in this submission were previously cleared under $510(\mathrm{k})$ K023944. All cross-reactivity and interference studies were done at that time. Please refer to the prior submission for specific information.

Urine samples up to $600,000\mathrm{mIU / mL}$ hCG cause no high-does hook effect. The sponsor provides references stating that this concentration of hCG is two to three times higher than levels found in pregnant individuals.

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# f. Assay cut-off:

Hormone levels greater than $25\mathrm{mIU / mL}$ are reported as positive. Hormone levels less than $25\mathrm{mIU / mL}$ are negative. Indeterminate results are reported as borderline and the user is prompted to retest in 48-72 hours.

# 2. Comparison studies:

a. Method comparison with predicate device:

A total of 3120 urine results were obtained at 4 sites using the Clinitek Status and Clinitest test strips. The same samples were read visually using a commercially available test kit (predicate device). The following results were obtained (38 samples were taken out of the analysis because visual readers were unwilling to say whether the tests were positive or negative using the predicate device):

| Clinitest hCG | Predicate test | | Total |
| --- | --- | --- | --- |
| | Negative | Positive | |
| Negative | 1996 | 10 | 2006 |
| | 98.2 % | 0.9 % | |
| Borderline | 27 | 2 | 29 |
| | 1.3 % | 0.2 % | |
| Positive | 9 | 1038 | 1047 |
| | 0.5 % | 98.9 % | |
| Total | 2032 | 1050 | 3082 |

The sponsor then assayed the discrepant results using a commercially available RIA kit to come up with the following agreements (note: the RIA kit is not cleared for quantitative measurement of hCG in urine):

| Clinitest hCG | Predicate test/RIA | | Total |
| --- | --- | --- | --- |
| | Negative | Positive | |
| Negative | 1999 | 3 | 2002 |
| | 99.7 % | 0.3 % | |
| Borderline | 7 | 7 | 14 |
| | 0.3 % | 0.6 % | |
| Positive | | 1051 | 1051 |
| | | 99.1 % | |
| Total | 2006 | 1061 | 3067 |

# b. Matrix comparison:

Not applicable.

# 3. Clinical studies:

a. Clinical sensitivity:

Not applicable. Patient samples were not clinically verified.

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b. Clinical specificity:

Not applicable. Patient samples were not clinically verified.

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

4. Clinical cut-off:
Not applicable.

5. Expected values/Reference range:
Not applicable.

M. Conclusion:

I recommend that the Bayer Healthcare Clinitest hCG Pregnancy Test for automatic reading on the Clinitek analyzer is substantially equivalent to the legally marketed predicate device.