ONE STEP HCG URINE PREGNANCY TEST (STRIP), MODEL B01-S, ONE STEP HCG URINE PREGNANCY TEST (CASSETTE) , MODEL B01C

K071930 · Blue Cross Bio-Medical Co., Ltd. · LCX · Dec 18, 2007 · Clinical Chemistry

Device Facts

• Record ID: K071930
• Device Name: ONE STEP HCG URINE PREGNANCY TEST (STRIP), MODEL B01-S, ONE STEP HCG URINE PREGNANCY TEST (CASSETTE) , MODEL B01C
• Applicant: Blue Cross Bio-Medical Co., Ltd.
• Product Code: LCX · Clinical Chemistry
• Decision Date: Dec 18, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1155
• Device Class: Class 2

Intended Use

One Step hCG Urine Pregnancy Test by Blue Cross is a visually-read, lateral flow immunoassay for the qualitative determination of human chorionic gonadotropin (hCG) in urine to help in the early detection of pregnancy by visual. The device is designed for over-the-counter use as well as professional use. Additional clinical examination should be performed to confirm the pregnancy.

Device Story

One Step hCG Urine Pregnancy Test is a lateral flow immunoassay available in strip, cassette, and midstream formats. It detects human chorionic gonadotropin (hCG) in urine samples. The device utilizes mouse monoclonal anti-beta-hCG antibody colloidal gold conjugate pre-dried on a pad; monoclonal anti-alpha-hCG antibodies and goat anti-mouse IgG are immobilized on a membrane. When urine contacts the membrane, it dissolves the conjugate; if hCG is present, it binds to the conjugate and is captured by the anti-alpha-hCG antibody at the test zone, forming a visible pink line. A control line forms via goat anti-mouse IgG binding. The test is performed by the user (professional or patient) and read visually. A positive result indicates hCG levels at or above the 25 mIU/mL cutoff. Results assist in early pregnancy detection, though additional clinical examination is required for confirmation.

Clinical Evidence

Bench testing only. Analytical performance: detection limit 25 mIU/mL; no cross-reactivity with LH (500 mIU/mL), FSH (2000 mIU/mL), or TSH (1000 mIU/mL); no interference from common drugs/analytes. Method comparison: 360 professional samples (100% agreement with predicate) and 360 OTC samples (100% agreement with predicate). User study confirmed ease of use for laypersons.

Technological Characteristics

Lateral flow immunochromatographic assay. Materials include mouse monoclonal anti-beta-hCG antibody colloidal gold conjugate, mouse monoclonal anti-alpha-hCG antibodies, and goat anti-mouse IgG immobilized on a membrane. Formats: strip, cassette, midstream. Qualitative visual readout. Calibrated against WHO 3rd IS (75/537). No electronic components or software.

Indications for Use

Indicated for the qualitative detection of hCG in urine to aid in early pregnancy detection. Intended for use by both professional healthcare providers and lay users (over-the-counter) who suspect pregnancy or have missed menses.

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

• WHPM One-Step Pregnancy Test (k041273, k012284)

Submission Summary (Full Text)

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

A. 510(k) Number:
k071930

B. Purpose for Submission:
new assay

C. Measurand:
human chorionic gonadotropin (hCG)

D. Type of Test:
lateral flow immunoassay (three formats: strip, cassette, and midstream)

E. Applicant:
Blue Cross Bio-medical (Beijing) Co., Ltd.

F. Proprietary and Established Names:
One Step HCG Urine Pregnancy Test

G. Regulatory Information:
1. Regulation section: 21 CFR 862.1155, chorionic gonadotropin test system
2. Classification: Class II
3. Product code: LCX, JHI
4. Panel: 75, Chemistry

H. Intended Use:
1. Intended use(s):
One Step hCG Urine Pregnancy Test by Blue Cross is a visually-read, lateral flow immunoassay for the qualitative determination of human chorionic gonadotropin (hCG) in urine to help in the early detection of pregnancy by visual. The device is

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designed for over-the-counter use as well as professional use. Additional clinical examination should be performed to confirm the pregnancy.

2. Indication(s) for use:
See intended use.

3. Special conditions for use statement(s):
For prescription and over-the-counter use
Additional clinical examination should be performed to confirm the pregnancy.

4. Special instrument requirements:
none

I. Device Description:

Blue Cross Biomedical’s One Step hCG Urine Pregnancy Test will be sold in three formats: test strip, cassette, and midstream. Each test device contains mouse monoclonal anti-beta-hCG antibody colloidal gold conjugate pre-dried on a pad. Mouse monoclonal anti-alpha-hCG antibodies (on test region) and goat anti-mouse IgG (on control region) are coated and immobilized on a membrane.

J. Substantial Equivalence Information:

1. Predicate device name(s): WHPM One-Step Pregnancy Test
2. Predicate K number(s): k041273 (professional use), k012284 (over the counter).
3. Comparison with predicate: The devices are similar in intended use, device design, material, test format, and principle. Specific reagents and antibodies vary.

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

Guidance for Over-the-Counter (OTC) Human Chorionic Gonadotropin (HCG) 510(k)s

Review Criteria for Assessment of Professional Use Human Chorionic Gonadotropin (HCG) In Vitro Diagnostic Devices (IVDs)

L. Test Principle:

The assay is based on an immunochromatographic technology. Each test device contains monoclonal anti-β hCG antibody colloidal gold conjugate pre-dried on a pad. Monoclonal anti-α hCG antibodies (on the test region) and goat anti-mouse IgG (on the control region) are coated and immobilized on a membrane. Other absorbent pads at the end of the assay absorb excess sample fluid. As the urine sample contacts the membrane, it dissolves the lyophilized conjugate. In a reactive sample, the hCG antigen will attach to

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the anti $\beta$ hCG monoclonal antibodies in the colloidal solution. As the conjugate moves forward on the membrane, anti- $\alpha$ hCG monoclonal antibody affixed on the test zone ("T") will bind the HCG-gold conjugate complex, forming a pink line. In addition, all samples will cause a pink colored line to appear in the control zone ("C"). This line is formed by the binding of the polyclonal antibodies (Anti-mouse IgG) affixed onto the control zone to the sample-colloidal gold conjugate. Presence of this line indicates sufficient sample volume was added.

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

# 1. Analytical performance:

# a. Precision/Reproducibility:

Standard solutions of hCG with varying concentrations were tested using ten strips from each lot for each concentration. Results are tabulated below. An additional study evaluating concentrations between 0 and $25\mathrm{mIU / mL}$ is shown in the detection limit study, below.

| HCG concentration | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- |
| | Pos | Neg | Pos | Neg | Pos | Neg |
| 0mIU/ml | 0 | 10 | 0 | 10 | 0 | 10 |
| 25mIU/ml | 10 | 0 | 10 | 0 | 10 | 0 |
| 50mIU/ml | 10 | 0 | 10 | 0 | 10 | 0 |
| 100mIU/ml | 10 | 0 | 10 | 0 | 10 | 0 |
| 100IU/ml | 10 | 0 | 10 | 0 | 10 | 0 |

# b. Linearity/assay reportable range:

Linearity is not applicable since this is a qualitative test.

The test was evaluated for high dose hook effect. Negative urine specimens were spiked with high hCG concentration of 62,500; 125,000; 250,000; 500,000; 1,000,000 and 2,000,000 mIU/mL. Both the test line and the control line were visible at these concentrations. (However, at concentrations over 250,000mIU/ml, the test lines become lighter).

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

One Step hCG Urine Pregnancy Test has been calibrated against reference material traceable to WHO $3^{\mathrm{rd}}$ IS (75/537).

# d. Detection limit:

The detection limit was evaluated by testing 40 hCG-negative urine samples,

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freshly collected, from healthy females. Each specimen was then divided into 7 portions and spiked to 0, 5, 12.5, 20, 25, 50 and 100 mIU/mL of hCG. Results of this testing are shown below.

| hCG concentration (mIU/mL) | 0 | 5 | 12.5 | 20 | 25 | 50 | 100 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| No. of Positive specimens | 0 | 0 | 4 | 22 | 40 | 40 | 40 |
| No. of Negative specimens | 40 | 40 | 36 | 18 | 0 | 0 | 0 |
| Total number | 40 | 40 | 40 | 40 | 40 | 40 | 40 |

e. Analytical specificity:

To evaluate cross-reactivity, 20 fresh urine specimens obtained from healthy non-pregnant females were spiked with different concentrations of Lutenizing Hormone (LH), Follicle stimulating Hormone (FSH), and thyroid stimulating hormone (TSH) into negative (0 mIU/mL) and positive (25mIU/ml) samples. The results demonstrated no cross reaction with LH at 500mIU/ml, FSH at 2000 mIU/mL, and TSH at 1000 mIU/mL. Results are tabulated below.

| | 500 mIU/mL hLH | 1000 mIU/mL hFSH | 1000 mIU/mL hTSH |
| --- | --- | --- | --- |
| No. of Positive samples | 0 | 0 | 0 |
| No. of Negative samples | 20 | 20 | 20 |
| | 500 mIU/mL hLH | 1000 mIU/mL hFSH | 1000 mIU/mL hTSH |
| --- | --- | --- | --- |
| No. of Positive specimens | 20 | 20 | 20 |
| No. of Negative specimens | 0 | 0 | 0 |

The standards used in this evaluation were: hLH, WHO 2nd IS (80/552); hFSH, WHO 2nd IRP (78/549); hTSH, WHO 2nd IRP (80/558).

Common prescription and OTC drugs, and chemical and biological analytes were added to negative (0 mIU/mL) and positive (25 mIU/mL) urine samples. The following substances, (or pH) at the indicated concentrations, were tested. No interference was observed. All hCG-negative urine specimens read negative and all hCG positive specimens read positive.

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| Analytes | Concentration |
| --- | --- |
| Acetaminophen | 20 mg/dl |
| Acetylsalicylic acid | 20 mg/dl |
| Ascorbic acid | 20 mg/dl |
| Caffeine | 20 mg/dl |
| Gentisic acid | 20 mg/dl |
| Phenylpropanolamine | 20 mg/dl |
| Salicylic acid | 20 mg/dl |
| Thiophene | 20 mg/dl |
| Ampicillin | 20 mg/dl |
| Tetracycline | 20 mg/dl |
| EDTA | 80 mg/dl |
| Benzoylecgonine | 10 mg/dl |
| Atropine | 20 mg/dl |
| Cannabinol | 10 mg/dl |
| Ethanol | 1% |
| Methanol | 1% |
| Albumin | 2,000 mg/dl |
| Glucose | 2,000 mg/dl |
| Bilirubin | 1,000 μg/dl |
| Hemoglobin | 1,000 μg/dl |
| pH 9 | |
| pH 8 | |
| pH 6 | |
| pH 5 | |
| pH 4 | |

f. Assay cut-off:

The test cutoff is set at 25 mIU/mL.

2. Comparison studies:

a. Method comparison with predicate device:

The performance of the three formats of the One Step HCG Urine Pregnancy test was compared to the predicate device. Studies were performed to evaluate the devices for both professional and OTC users.

Professional Use

Studies were conducted at three hospital laboratories. A total of 360 fresh urine samples (120 samples from each site) were collected during any time of the day from patients who visited the ob-gyn department of three hospitals. Patients included women who suspected pregnancy, and who had late periods, as well as those later in pregnancy. There were over 30 positive samples from women in

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early pregnancy (defined by the sponsor as 35 days or less since last menstrual period). Medical professionals from the hospitals read the package inserts and conducted assays with the new and predicate devices side by side. Overall results are tabulated below.

| All three hospitals | Currently marketed hCG device (+) | Currently marketed hCG device (-) | Total |
| --- | --- | --- | --- |
| One Step HCG Urine Pregnancy Test (+) | 213 | 0 | 213 |
| One Step HCG Urine Pregnancy Test (-) | 0 | 147 | 147 |
| Total | 213 | 147 | 360 |

Over the Counter Use

A total of 360 women were enrolled to conduct the Blue Cross Biomedical One Step hCG Urine Pregnancy Test and the predicate device. This included 120 using each of the 3 formats. The age of these subjects ranged from 15 to 56 years of age, and their education level range from middle school to PhD. This study group included women who were pregnant, women who had missed menses, women who were not pregnant, women who are postmenopausal, and women who are infertile. Each test was run and interpreted according to its package insert and was performed by the subject without supervision. A summary of the results is tabulated below:

| | Currently Marketed HCG device (+) | Currently Marketed HCG device (-) | Total |
| --- | --- | --- | --- |
| One Step HCG Urine Pregnancy Test strips (+) | 65 | - | 65 |
| One Step HCG Urine Pregnancy Test strips (-) | - | 55 | 55 |
| | | | |
| One Step HCG Urine Pregnancy Test cassette (+) | 66 | - | 66 |
| One Step HCG Urine Pregnancy Test cassette (-) | - | 54 | 54 |
| | | | |
| One Step HCG Urine Pregnancy Test midstream (+) | 67 | - | 67 |
| One Step HCG Urine Pregnancy Test midstream (-) | - | 53 | 53 |
| Grand Total | 198 | 162 | 360 |

After recording their results, participants were asked to evaluate the test. All participants thought the test was either "very easy" or "easy" to read and interpret (on a scale ranging from very difficult to very easy).

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-b. Matrix comparison:

Not applicable. The device is for use with urine samples only.

3. Clinical studies:

a. Clinical Sensitivity:

Not typically provided for this device type.

b. Clinical specificity:

Not typically provided for this device type.

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

4. Clinical cut-off:

The test cutoff is set at 25 mIU/mL.

5. Expected values/Reference range:

Not applicable – this is a qualitative test.

N. Proposed Labeling:

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

O. Conclusion:

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