The Clearblue® Early Pregnancy Test is an over-the-counter chromatographic immunoassay for the qualitative detection of human chorionic gonadotropin (hCG) in urine. This test is intended for use as an aid in early detection of pregnancy, in some cases as early as six (6) days before the day of the missed period, i.e. as early as five (5) days before the day of the expected period.

The test is intended for home use.

Device Description

The Clearblue® Early Pregnancy Test is an over-the-counter (OTC), visual pregnancy test and is indicated for use up to 6 days before the missed period (5 days before expected period). The device employs an immunochromatographic sandwich assay to detect hCG on a lateral flow test strip.

The test incorporates a proprietary, FSH modulated, hCG scavenger system positioned upstream of the hCG test line to maintain high specificity to pregnancy. The scavenger system captures hCG when there are high levels of FSH in the sample. This ensures that hCG is removed from samples with elevated levels of FSH, reducing the chance of false positive results which while rare, may occur in some women.

The result is displayed to the user in the test window as two lines for a 'Pregnant' result and one line for a `Not Pregnant' result.

AI/ML Overview

The provided document describes the performance and testing of the "Clearblue® Early Pregnancy Test," a qualitative immunoassay for detecting human chorionic gonadotropin (hCG) in urine. This document pertains to its 510(k) premarket notification (K213379) to the FDA.

Here's a breakdown of the acceptance criteria and study proving device performance, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly list "acceptance criteria" in a table format with pass/fail remarks. However, the performance characteristics sections imply certain criteria are met for the device to be considered substantially equivalent. Based on the studies, here is a summary of the implicit criteria and reported performance:

Performance Metric (Implicit Acceptance Criteria)	Reported Device Performance (Clearblue® Early Pregnancy Test)
Accuracy (Lay User Study vs. Clinical Status)	100% agreement (PPV, NPV, Sensitivity, Specificity)
- Pregnant Cohort	100% detection (152/152 pregnant samples correctly identified)
- Not Pregnant Cohort	100% negative results (143/143 not pregnant samples correctly identified)
Accuracy (Lay User vs. Technician)	100% agreement between lay user and technician results
Precision/Reproducibility	Consistent results across technicians, batches, and days, especially at 10 mIU/ml hCG and above (100% pregnant results).
- 10 mIU/ml hCG	100% Pregnant results
- 15 mIU/ml hCG	100% Pregnant results
- 20 mIU/ml hCG	100% Pregnant results
- <1 mIU/ml hCG	0% Pregnant results
- 2 mIU/ml hCG	0% Pregnant results
Detection Limit (Sensitivity)	Consistent detection at 10 mIU/ml hCG (100% positive results reported).
Early Pregnancy Detection (Clinical Samples)	Detects 100% of pregnancies by Day -3 (relative to missed period); 77.5% by Day -6; 93.6% by Day -5; 98.0% by Day -4.
High Dose Hook Effect	No hook effect observed up to 1,000,000 mIU/ml hCG.
Analytical Specificity (Interfering Substances)	No interference observed for a variety of common substances at specified concentrations.
Analytical Specificity (Cross Reactants)	No false positives with LH, TSH, high FSH (at specified concentrations). Correct results for hCG negative and positive samples with cross-reactants.
Effect of Urine pH	Correct results within pH range of 4-9.
Effect of Urine Specific Gravity	Correct results within specific gravity range of 1.000 to 1.035.
Effect of hCG beta core fragment (hCGβcf)	Performance not affected by high concentrations of hCGβcf.
Specificity Study (False Positive Rate)	100% specificity across pre-menopausal, peri-menopausal, and post-menopausal not-pregnant cohorts (no false positives).

2. Sample Sizes Used for the Test Set and Data Provenance

The document describes several test sets:

Precision/Reproducibility Study:
- Sample Size: For each hCG concentration, 135 tests were performed (e.g., at 10 mIU/ml, 135 pregnant results recorded). This was broken down by 3 batches (90 samples per batch per concentration) and 3 technicians (90 samples per technician per concentration) and 5 nonconsecutive days (54 samples per day per concentration). Total tests performed across all concentrations, methods, batches, and technicians sums to (8 concentrations * 2 methods * 3 batches * 5 replicates = 240) which does not match the 135 per concentration in the table. The "Total" column suggests (135 tests per concentration). Each combination of hCG standard, method (dip/in-stream), technician, and day was tested.
- Data Provenance: Not explicitly stated (e.g., country of origin), but implies laboratory/analytical testing within a controlled environment. Retrospective/Prospective is not stated but suggests controlled laboratory testing.
Detection of hCG in Early Pregnancy Clinical Samples:
- Sample Size:
  - Day -10: 42 samples
  - Day -9: 72 samples
  - Day -8: 120 samples
  - Days -7 to 0: 204 samples per day
- Data Provenance: "Early pregnancy urine samples from days -10 to 0 relative to the day of the missed period were collected." This indicates prospective collection from pregnant women. No country of origin is specified.
Lay User Study:
- Sample Size:
  - Overall: 295 volunteers (152 clinically pregnant, 143 clinically not-pregnant).
  - In-stream method: 116 (59 pregnant, 57 not-pregnant).
  - Dip method: 179 (93 pregnant, 86 not-pregnant).
- Data Provenance: "Pregnant and not pregnant women volunteers with diverse educational and professional backgrounds and ages between 18 and 55 years old participated..." This is prospective data collected from volunteers. No country of origin is specified.
Lay User Spiked Standard Study:
- Sample Size: Varies per hCG standard: 107 samples at 0 mIU/ml, 107 at 2 mIU/ml, 103 at 3 mIU/ml, 106 at 5 mIU/ml, 105 at 10 mIU/ml, 108 at 15 mIU/ml.
- Data Provenance: Spiked urine standards. This is controlled laboratory testing, likely prospective in nature for the study.
Specificity Study (False-Positive Rate):
- Sample Size: 899 not-pregnant women (300 pre-menopausal, 299 peri-menopausal, 300 post-menopausal).
- Data Provenance: "Urine samples were collected from individual women of each cohort." This indicates prospective sample collection from various age groups.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts

For the "Detection of hCG in Early Pregnancy Clinical Samples" and "Lay User Study": The ground truth for pregnancy status was established by "physician determined clinical pregnancy status." The number or specific qualifications (e.g., years of experience) of these physicians are not specified.
For the "Analytical Performance" studies (Precision, Specificity, etc.): Ground truth was based on spiked hCG concentrations traceable to the WHO 4th International Standard, and known concentrations of interfering/cross-reacting substances. This does not rely on human "experts" to establish ground truth in the same way clinical studies do.

4. Adjudication Method for the Test Set

Clinical Ground Truth: For the "Lay User Study" and "Detection of hCG in Early Pregnancy Clinical Samples," the ground truth was "physician determined clinical pregnancy status." There is no mention of an adjudication method (e.g., multiple physicians, consensus, tie-breaking) for discrepancies, suggesting a single physician's determination was used, or implicitly that the clinical status was clear and undisputed.
Analytical Studies: Ground truth for these studies was based on controlled scientific measurements (known concentrations of hCG, interfering substances, etc.), so no human adjudication method was required.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study was not explicitly stated or described as being performed.

The "Lay User Study" is a form of multi-reader study (multiple lay users reading the device), but it compares lay user results against clinical status and technician results, not against AI assistance. The document explicitly states: "The Lay User Usage study collected the lay users and technician results and compared them against physician determined clinical pregnancy status, hence the comparison to the predicate device was not performed." There is no mention of AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done

This device is a physical, over-the-counter visual pregnancy test. It is not an AI/algorithm-driven device. Therefore, a standalone (algorithm-only) performance study is not applicable and was not conducted. The "performance" in this context refers to the chemical immunoassay and interpretation by human users.

7. The Type of Ground Truth Used

Clinical Studies (Early Pregnancy Detection & Lay User Study): The ground truth for pregnancy status was physician determined clinical pregnancy status.
Analytical Studies (Precision, Sensitivity, Specificity, etc.): The ground truth was based on known concentrations of hCG (traceable to WHO 4th International Standard) and controlled laboratory conditions using spiked urine samples with known concentrations of various substances.

8. The Sample Size for the Training Set

This document describes a diagnostic device (an immunoassay), not an AI/machine learning algorithm. Therefore, there is no concept of a "training set" for an algorithm. The performance studies described serve as validation studies for the device itself.

9. How the Ground Truth for the Training Set was Established

As there is no AI/machine learning algorithm involved, and thus no "training set," this question is not applicable.

Summary

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September 21, 2022

SPD Swiss Precision Diagnostics GmbH % Kamila Przedmojska Principal Regulatory Affairs Specialist SPD Development Company Limited Priory Business Park, Stannard Way Bedford, Bedfordshire MK44 3UP United Kingdom

Re: K213379

Trade/Device Name: Clearblue® Early Pregnancy Test Regulation Number: 21 CFR 862.1155 Regulation Name: Human Chorionic Gonadotropin (hCG) Test System Regulatory Class: Class II Product Code: LCX Dated: June 24, 2022 Received: July 5, 2022

Dear Kamila Przedmojska:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K213379

Device Name Clearblue® Early Pregnancy Test

The test is intended for home use.

Type of Use ( Select one or both, as applicable )	Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C)	Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)

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Image /page/3/Picture/2 description: The image shows the logo for Swiss Precision Diagnostics GmbH. The logo features the letters "SPD" in a stylized font, with the letters arranged in a circular shape. The circle is colored with a gradient that transitions from blue at the top to green at the bottom. To the right of the circle, the text "Swiss Precision Diagnostics GmbH" is written in a simple, sans-serif font.

510(k) Summary

A. Submitted By:	SPD Swiss Precision Diagnostics GmbH47 Route de Saint-GeorgesPetit-LancyCH-1213GenevaSwitzerlandTelephone: +41 580048741
B. Contact Person:	Kamila PrzedmojskaPrincipal Regulatory Affairs SpecialistSPD Development Company LimitedPriory Business ParkBedfordMK44 3UPUnited KingdomTelephone: +44 1234835504
C. Date Prepared:	24 June, 2022
D. Device Name:	Clearblue® Early Pregnancy Test
Product Code:	LCX
Common name:	Kit, Test, Pregnancy, hCG, over the counter
Classification:	Class II
Product code:	LCX
Regulation Description:	Human chorionic gonadotropin (hCG) test system
Regulation number:	21CFR 862.1155
E. Predicate Device:	FIRST RESPONSE™ Early Result Pregnancy Test(K123436)

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F. Indication for Use

Clearblue® Early Pregnancy Test is an over-the-counter The chromatographic immunoassay for the qualitative detection of human chorionic gonadotropin (hCG) in urine. This test is intended for use as an aid in early detection of pregnancy, in some cases as early as six (6) days before the day of the missed period, i.e. as early as five (5) days before the day of the expected period.

The test is intended for home use.

G. Device Description

The result is displayed to the user in the test window as two lines for a 'Pregnant' result and one line for a `Not Pregnant' result.

H. Substantial Equivalence Information

Predicate device name: FIRST RESPONSE™ Early Result Pregnancy Test

Predicate (k) number: K123436

Comparison with predicate:

Table 1 Similarities and differences between Clearblue® Early Pregnancy Test and the predicate FIRST RESPONSE™ Early Results Pregnancy Test

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Component	Clearblue® Early PregnancyTest (Proposed Device)	FIRST RESPONSE™ EarlyResult Pregnancy Test(Predicate Device)
		Similarities
Intended Use	Qualitative detection of humanhCG for an aid in early detectionof pregnancy	Same
'Early Test'Claim	in some cases as early as six (6)days before the day of the missedperiod, i.e. as early as five (5)days before the day of theexpected period.	Same
Target User	Over-The-Counter use	Same
Device format	Single Use	Same
Sample Matrix	Urine	Same
Analyte	hCG	Same
Sampleapplication	In-stream and dip	Same
hCGSensitivity	10mIU/ml	Same
Traceability	WHO 4th International Standardfor hCG	Same
Test Principle	Lateral flow sandwich immuno-chromatographic assay	Same
Assay MobilePhase	Gold conjugate	Same
Test Type	Qualitative	Same
ControlMechanism	Visual	Same
ResultsDisplay	Visual Parallel Line2 Lines = Pregnant1 Line = Not Pregnant	Same
		Differences
AnalyteDetection	Detects intact hCG.Scavenger system to removeintact hCG in the presence ofFSH.	Recognises: intact hCGhyperglycosylated hCGhCG ẞ-subunithCG ẞ-core fragment
Time toresults	5 minutes	3 minutes

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I. Test Principle

The Clearblue® Early Pregnancy test is a lateral flow sandwich immunoassay employing monoclonal antibodies that are specifically directed against the alpha and beta sub-units of hCG.

To use the Clearblue® Early Pregnancy test, the user either urinates directly onto the absorbent wick or collects a sample in a container and dips the absorbent wick into the collected sample.

Buffer salts in the wick are dissolved by the sample, normalising the pH and ionic strength to provide suitable conditions for the down-stream immunoassay. Upon wetting of the wick, urine is drawn by capillary action into the conjugate pad. As the sample moves from the wick through the conjugate release pad, the antibody coated gold-sol particles are mobilized and transported along the test strip. Any hCG and/or FSH in the sample will bind to the test gold-sol label via their common alpha sub-unit.

On reaching the nitrocellulose membrane, the sample is drawn across the plotted line of immobilised anti-beta FSH antibody in the scavenger zone which is not visible to the user as it is located within the plastic case moulding. The sample then progresses across the monoclonal anti-beta hCG antibody test line and polyclonal anti-rabbit antibody control line and on to the distal end of the test strip into the sink pad.

J. Performance characteristics

1. Analytical Performance

a) Precision/Reproducibility

A not-pregnant pooled urine was spiked with hCG traceable to the 4th WHO international standard with hCG concentrations of <1, 2, 3, 5, 7, 10, 15 and 20 mIU/ml. Each standard was tested with devices from three different batches using both dip and simulated in-stream sampling methods. The study was performed by three technicians over five nonconsecutive days.

The results are summarised in the tables below:

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	Clearblue® Early Pregnancy Test Overall Results
hCGStandard	Dip method			Simulated in stream method			Total
(mIU /ml)	NotPregnant(n)	Pregnant(n)	PregnantResults(%)	NotPregnant(n)	Pregnant(n)	PregnantResults(%)	Pregnant(%)
<1	135	0	0.0	135	0	0.0	0.0
2	135	0	0.0	135	0	0.0	0.0
3	102	33	24.4	100	35	25.9	25.2
5	43	92	68.1	42	93	68.9	68.5
7	16	119	88.1	18	117	86.7	87.4
10	0	135	100.0	0	135	100.0	100
15	0	135	100.0	0	135	100.0	100
20	0	135	100.0	0	135	100.0	100

Overall Precision Results of Clearblue® Early Pregnancy Test

Percentage Pregnant Results for Each hCG Standard by Technician

hCGStandard(mIU/ml)	Technician 1		Technician 2		Technician 3
	Pregnant/NotPregnant(n)	PregnantResults(%)	Pregnant/NotPregnant(n)	PregnantResults(%)	Pregnant/NotPregnant(n)	PregnantResults(%)
<1	0/90	0.0	0/90	0.0	0/90	0.0
2	0/90	0.0	0/90	0.0	0/90	0.0
3	21/69	23.3	23/67	25.6	24/66	26.7
5	59/31	65.6	62/28	68.9	64/26	71.1
7	77/13	85.6	78/12	86.7	81/9	90.0
10	90/0	100	90/0	100	90/0	100
15	90/0	100	90/0	100	90/0	100
20	90/0	100	90/0	100	90/0	100

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hCGStandard(mIU/ml)	Batch 1		Batch 2		Batch 3
	Pregnant/NotPregnant(n)	PregnantResults(%)	Pregnant/NotPregnant(n)	PregnantResults(%)	Pregnant/NotPregnant(n)	PregnantResults(%)
<1	0/90	0.0	0/90	0.0	0/90	0.0
2	0/90	0.0	0/90	0.0	0/90	0.0
3	25/65	27.8	22/68	24.4	21/69	23.3
5	63/27	70.0	63/27	70.0	59/31	65.6
7	79/11	87.8	80/10	88.9	77/13	85.6
10	90/0	100	90/0	100	90/0	100
15	90/0	100	90/0	100	90/0	100
20	90/0	100	90/0	100	90/0	100

Percentage Pregnant Results for Each hCG standard by Batch

Percentage Pregnant Results for Each hCG standard by Day

hCGStandard(mIU /ml)	Day 1		Day 2		Day 3		Day 4		Day 5
	P/NP(n)	PregnantResults(%)	P/NP(n)	PregnantResults(%)	P/NP(n)	PregnantResults(%)	P/NP(n)	PregnantResults(%)	P/NP(n)	PregnantResults(%)
< 1	0/54	0.0	0/54	0.0	0/54	0.0	0/54	0.0	0/54	0.0
2	0/54	0.0	0/54	0.0	0/54	0.0	0/54	0.0	0/54	0.0
3	14/40	25.9	14/40	25.9	11/43	20.4	15/39	27.8	14/40	25.9
5	39/15	72.2	36/18	66.7	37/17	68.5	35/19	64.8	38/16	70.4
7	47/7	87.0	49/5	90.7	46/8	85.2	44/10	81.5	50/4	92.6
10	54/0	100	54/0	100	54/0	100	54/0	100	54/0	100
15	54/0	100	54/0	100	54/0	100	54/0	100	54/0	100
20	54/0	100	54/0	100	54/0	100	54/0	100	54/0	100

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b) Linearity/assay reportable range:
Not applicable. This is a qualitative device.
c) High dose hook effect study:
A not-pregnant pooled urine was spiked with hCG to concentrations of <1, 10, 10,000 and 1,000,000mIU/ml and tested with 5 replicates from each of three batches. No hook effect was observed at the tested concentrations.

d) Traceability

The tests are calibrated against the WHO 4th International Standards for human Chorionic Gonadotropin (hCG).

e) Stability
The claimed shelf life of the device stored in the sealed foil pouches at room temperature is 39 months.
f) Detection Limit (Sensitivity)
See Precision/Reproducibility section.
g) Analytical Specificity

Structurally not-related compounds

Interfering substances

The Clearblue® Early Pregnancy Test devices were tested with potential interfering substances. Each interfering substance was spiked into nonpregnant pooled urine and 10mIU/ml hCG urine standards.

Each condition was tested with 5 devices from each of three batches of the Clearblue® Early Pregnancy Test for each of the two urine standards according to the dip sampling method. No interference effect was observed at the tested concentrations shown in the table below:

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Interfering Substance	Concentration
Acetylsalicylic acid	1.0mg/ml
Acetone	1.0mg/ml
Albumin	5mg/ml
Ampicillin	20 mg/dL
Ascorbic acid	150µg/ml
Atropine	200 µg/mL
Bilirubin	20 mg/dL
Blood	0.3% v/v
Caffeine	1.2mg/ml
Cannabinol	10 mg/dL
Clomiphene citrate	24µg/ml
Cotinine	40 µg/ml
Ethanol	1% v/v
E3G	620ng/ml
Gentisic acid	20 mg/dL
Glucose	20mg/ml
Haemoglobin	100µg/ml
Hydrochloric acid	1.25mM
Ibuprofen	100µg/ml
Leukocytes	x106 cells/ml
Oxytetracycline	300µg/ml
Paracetamol (Acetaminophen)	600µg/ml
Phenylpropanolamine	20 mg/dL
P3G	40µg/ml
Semen	5% v/v
Sodium hydroxide	1.25mM
Tetracycline	300µg/ml
Urea	30mg/ml
Uric acid	750µg/ml

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Structurally related compounds

Effects of cross reactants

The results in the table below show that all the devices tested returned the correct result when tested with potential cross reactants at the concentrations shown below.

	Result
Standards	Pregnant (n)	Not Pregnant(n)	Pass/Fail
<1 hCG mIU/ml	0	15	Pass
10 hCG mIU/ml	15	0	Pass
<1 hCG mIU/ml, 500 LH mIU/ml	0	15	Pass
10 hCG mIU/ml, 500 LH mIU/ml	15	0	Pass
<1 hCG mIU/ml, 1 TSH mIU/ml	0	15	Pass
10 hCG mIU/ml, 1 TSH mIU/ml	15	0	Pass
<1 hCG mIU/ml, 1000 FSH mIU/ml	0	15	Pass
10 hCG mIU/ml, 15 FSH mIU/ml	15	0	Pass
4 hCG mIU/ml, 100 FSH mIU/ml	0	30	Pass
4 hCG mIU/ml, 1000 FSH mIU/ml	0	30	Pass
4 hCG mIU/ml, 100 FSH mIU/ml, 1 TSHmIU/ml	0	30	Pass
4 hCG mIU/ml, 100 FSH mIU/ml, 500LH mIU/ml	0	30	Pass

Effects of urine pH

Effect of urine pH was performed by adjusting negative (<1 mIU/ml) and 10mIU/ml hCG urine standards to a pH range of 4, 6 and 9. Each urine standard was tested with 5 devices from each of 3 batches by dip sampling method. The results demonstrated that Clearblue® Early Pregnancy Test will continue to return a correct result when tested with a urine sample in the pH range of 4 – 9.

Effect of urine specific gravity

To test the effect of specific gravity, the device was challenged with nonpregnant pooled urine and positive (10mIU/ml hCG) urine standards with specific gravity of 1.000, 1.01, 1.015, 1.03 and 1.035. Each urine standard

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was tested with 5 devices from each of 3 batches by dip sampling method. The results showed the Clearblue® Early Pregnancy Test will continue to return a correct result in response to changes in specific gravity within the range from 1.000 to 1.035.

Effect of hCG beta core fragment (hCGβcf)

To evaluate the effect of hCGβcf, 11 conditions were tested with 5 devices from each of 3 batches, totalling 165 devices.

Pooled pregnant urine collected from 6-7 weeks and 9-12 weeks pregnancy were tested with and without hCGßcf spiked up to 1µM.

Pooled neqative urine spiked with hCG to a concentration representative of 6-7 weeks and 9-12 weeks pregnant urine samples were tested with and without hCGβcf spiked up to 1μM.

A non-pregnant pooled urine was spiked to 10mIU/ml hCG then spiked with 150pM hCGβcf (a concentration 5 times the molar concentration of intact hCG) was tested. Positive (negative pooled urine spiked to 10mIU/ml) and non-pregnant (<1.0 mIU/ml) controls were also tested.

The results show that the performance of the Clearblue® Early Pregnancy Test is not affected by high concentrations of hCG β-core fragment.

h) Assay cut-off

See Precision/Reproducibility Section.

2. Comparison Study

a. Method comparison with predicate device:
The Lay User Usage study collected the lay users and technician results and compared them against physician determined clinical pregnancy status, hence the comparison to the predicate device was not performed.

b. Matrix comparison:

Not Applicable. The device is intended for urine sample only.

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1. Clinical Studies
a. Clinical Sensitivity:

Not Applicable

b. Clinical Specificity:
Not Applicable

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

Detection of hCG in Early Pregnancy Clinical Samples

Early pregnancy urine samples from days -10 to 0 relative to the day of the missed period were collected. Each sample was tested using both methods of sampling across three batches of devices.

The early pregnancy detection results are summarised in table below:

Day Relative toMissed Period	Total Samples(n)	NumberPregnant Result(n)	PercentPregnant Result(%)
-10	42	0	0.0
-9	72	0	0.0
-8	120	6	5.0
-7	204	58	28.4
-6	204	158	77.5
-5	204	191	93.6
-4	204	200	98.0
-3	204	204	100
-2	204	204	100
-1	204	204	100
0	204	204	100

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Lay User Study

Pregnant and not pregnant women volunteers with diverse educational and professional backgrounds and ages between 18 and 55 years old participated in the Lay User Usage Study. Their results were compared to their clinical pregnancy status and to the results obtained from trained technicians testing the same urine samples in the same sampling method (either simulated in-stream or dipping).

The study confirmed that PPV, NPV, sensitivity, specificity and accuracy for the Clearblue® Early Pregnancy Test in the hands of lay-user volunteers was 100%, for both dip and in-stream testing methods.

The agreement between lay-user volunteer results and their clinical status with the Clearblue® Early Pregnancy Test was 100%. There was also 100% agreement between all lay-user volunteer results and technician results.

The results are summarised in tables below:

Volunteer (both in-stream and dip results combined) vs clinical pregnancy status.

Clinical PregnancyStatus	Volunteer Result
	Pregnant	NotPregnant	Total
Pregnant	152	0	152
Not Pregnant	0	143	143
Total	152	143	295

Volunteer (In-stream) results vs clinical pregnancy status

Clinical PregnancyStatus	Volunteer Result
	Pregnant	NotPregnant	Total
Pregnant	59	0	59
Not Pregnant	0	57	57
Total	59	57	116

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Volunteer (Dip) results vs clinical pregnancy status

Clinical Pregnancy	Volunteer Result
Status	Pregnant	NotPregnant	Total
Pregnant	93	0	93
Not Pregnant	0	86	86
Total	93	86	179

Volunteer results vs technician result

Technician TestResults	Volunteer Result
	Pregnant	NotPregnant	Total
Pregnant	152	0	152
Not Pregnant	0	143	143
Total	152	143	295

Lay User Spiked Standard Study

A study was performed to analyse the performance of the Clearblue® Early Pregnancy Test when read by lay user according to the Instructions for Use. A range of the hCG urine standards at 0, 2, 3, 5, 10 and 15mIU/ml were sampled by dip method of sampling and read by lay users. The results are shown in table below:

hCG Standard(mIU/ml)	Total (n)	NumberPregnant(n)	PercentPregnant(%)
0	107	0	0.0
2	107	2	1.9
3	103	28	27.2
5	106	74	69.8
10	105	105	100
15	108	108	100

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Specificity study to determine false-positive result rate

A study was performed to determine the incidence of false positive results among not-pregnant women of pre-menopausal age (18-40 years), perimenopausal age (41-55 years) and post-menopausal age (>55 years). Urine samples were collected from individual women of each cohort and were tested by technicians with three batches of the Clearblue® Early Pregnancy Test devices by both dip and simulated in-stream method of sampling.

The results (combined method of sampling) are summarised in table below:

Cohort	Not Pregnant(n)	Samples(n)	Specificity(%)
Pre-menopausal	300	300	100
Peri-menopausal	299	299	100
Post-menopausal	300	300	100
All Not Pregnant	899	899	100

Clinical Cut-off

Not applicable.

Expected value

Not applicable.

K. Conclusion

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

Regulation Number and Section

§ 862.1155 Human chorionic gonadotropin (HCG) test system.

(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)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.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. 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.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.