The Clearblue® Early Digital Pregnancy Test is an over-the-counter chromatographic immunoassay for the qualitative detection of human chorionic gonadotropin (hCG) in urine. This digital 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 Digital Pregnancy Test is an over-the-counter (OTC), digital pregnancy test with sensitivity to 10mIU/ml hCG (hormone human chorionic gonadotrophin) 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 result is displayed to the user, in words, on an LCD.

AI/ML Overview

The Clearblue® Early Digital Pregnancy Test is an over-the-counter chromatographic immunoassay designed for the qualitative detection of human chorionic gonadotropin (hCG) in urine. It is intended as an aid in the early detection of pregnancy, up to six days before a missed period.

Here's the breakdown of its acceptance criteria and the supporting study:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a bulleted or numbered list with predefined thresholds. Instead, the performance characteristics are presented as evidence of the device's capability and equivalence to a predicate device. Based on the provided data, the implied acceptance criteria would revolve around:

Analytical Sensitivity: Ability to detect hCG at a specified concentration (e.g., 10 mIU/ml).
Analytical Cut-off: The hCG concentration at which approximately half of the devices yield positive results.
Specificity: No significant interference from common substances or cross-reactivity with related hormones.
Lay User Performance: High agreement with clinical pregnancy status and technician results when used by laypersons.
Early Detection Claim: Demonstrated detection rates at various days relative to the missed period.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Analytical Sensitivity	Detect hCG at 10 mIU/ml with high accuracy (e.g., 100% positive)	100% positive results at 10 mIU/ml hCG concentration (both dip and simulated in-stream methods across technicians and days).
Analytical Cut-off	To be determined and reported.	Determined as 7.6 mIU/ml.
Interfering Substances	No interference at specified concentrations.	No interference observed at tested concentrations for various substances (e.g., Acetylsalicylic acid, Acetone, Albumin, Glucose, Haemoglobin, etc.) up to 10 mIU/ml hCG.
Cross-reactivity	No cross-reactivity with specified hormones.	No cross-reactivity observed at tested concentrations for Follicle-Stimulating Hormone (FSH) (1000 mIU/ml), Luteinizing Hormone (LH) (500 mIU/ml), and Thyroid-Stimulating Hormone (TSH) (1 mIU/ml).
Effect of Urine pH	Correct results across physiological pH range.	Correct results observed within a pH range of 4-9.
Effect of Urine Specific Gravity	Correct results across physiological specific gravity range.	Correct results observed within a specific gravity range of 1.000 to ≤1.035.
Effect of hCG beta core fragment	Performance not affected by high concentrations.	Performance not affected by high concentrations of hCG β-core fragment.
Method Comparison with Predicate	High agreement with predicate device and clinical status.	99.5% agreement with the FIRST RESPONSE™ Gold Digital Pregnancy Test. 100% agreement with the clinical status of volunteers' urine samples.
Early Pregnancy Detection	Detection rates supporting early claim (e.g., 6 days before MPs).	Shows varied detection rates: 78.4% at -6 days, 93.1% at -5 days, 99.0% at -4 days, and 100.0% from -3 to -1 days relative to the missed period. (Claim: as early as six days before the missed period).
Lay User Study Performance	High Positive Predictive Value (PPV), Negative Predictive Value (NPV), Sensitivity, Specificity, and Accuracy. High agreement between lay-user results, clinical status, and technician results.	100% PPV, NPV, sensitivity, specificity, and accuracy when used by lay users, for both dip and in-stream testing methods, compared to clinical pregnancy status. 100% agreement between lay-user volunteer results (in-stream vs dip) and clinical status. 100% agreement between all lay-user volunteer results and technician dip results.
Specificity (False-Positive Rate)	Low false-positive rate across age cohorts.	100.0% specificity for pre-menopausal and peri-menopausal women. 99.3% specificity for post-menopausal women (1 false positive out of 150 attributed to an hCG concentration of 7.83 mIU/ml, which is above the analytical cut-off). Overall specificity: 99.8% (449/450).
Lay User Spiked Standard Study (Detection Rates)	Detect 10 mIU/ml hCG with 100% accuracy, graded detection below that.	100% detection at 10 mIU/ml. 74% detection at 8.5 mIU/ml. 50% detection at 7.5 mIU/ml. 0% detection at 3 mIU/ml.

2. Sample Sizes and Data Provenance

Test Set for Analytical Performance (Precision/Reproducibility):
- Sample Size: For each of the nine hCG standards, 324 total samples were tested (162 with dip method, 162 with simulated in-stream method). This was further broken down by technicians and days (e.g., 108 samples per technician/day for each standard).
- Data Provenance: Not explicitly stated, but implies laboratory-prepared spiked urine samples. No country of origin is specified, but the applicant addresses are in Switzerland and the UK. This is prospective for the test devices.
Test Set for Method Comparison with Predicate Device:
- Sample Size: 102 urine samples from pregnant women and 102 urine samples from non-pregnant women.
- Data Provenance: Not explicitly stated, but refers to "urine samples from pregnant women" and "not pregnant women," suggesting retrospective clinical samples or samples collected for the study. No country of origin for samples is specified.
Test Set for Early Pregnancy Detection (Clinical Samples):
- Sample Size: 831 early pregnancy urine samples from days -10 to -1 relative to the day of the missed period.
- Data Provenance: Clinical samples. No country of origin is specified.
Test Set for Lay User Study (Clinical Samples):
- Sample Size: 394 volunteers (205 not pregnant, 189 pregnant).
- Data Provenance: Volunteers. No country of origin is specified.
Test Set for Specificity Study (False-positive rate):
- Sample Size: 450 urine samples (150 from pre-menopausal, 150 from peri-menopausal, 150 from post-menopausal women).
- Data Provenance: Clinical samples. No country of origin is specified.
Test Set for Lay User Spiked Standard Study:
- Sample Size: 200 samples per hCG standard (3, 7.5, 8.5, 10 mIU/ml), totaling 800 samples.
- Data Provenance: Laboratory-prepared spiked urine samples, tested by lay users. No country of origin is specified.

3. Number of Experts and Qualifications for Ground Truth

For Analytical Performance (Precision/Reproducibility): 3 technicians performed the testing. Their specific qualifications are not detailed beyond "trained technicians."
For Method Comparison with Predicate Device: "Trained technicians" performed the testing.
For Early Pregnancy Detection (Clinical Samples): There is no mention of experts establishing ground truth for these samples, but it's implied that the "Days Relative to Missed Period" serves as the clinical ground truth for assessing early detection.
For Lay User Study: Technician results via dip method and the "clinical pregnancy status" of the volunteers served as ground truth. The qualifications of these technicians are not explicitly stated, but their role suggests expertise in properly performing and interpreting the test.
For Specificity Study: Technicians performed the testing. The "clinical status" of the non-pregnant women was the ground truth.
For Lay User Spiked Standard Study: Lab-prepared hCG standards define the ground truth.

4. Adjudication Method for the Test Set

No explicit adjudication method (e.g., 2+1, 3+1) is mentioned for any of the studies. All results appear to be direct observations or comparisons to established clinical status or laboratory standards.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study comparing human readers with AI assistance versus without AI assistance was done. The device is a standalone in-vitro diagnostic (IVD) device, not an AI-assisted diagnostic tool for human readers.

6. Standalone Performance Study

Yes, a standalone performance study (algorithm only, without human-in-the-loop performance) was performed. The "Analytical Performance" section, particularly the Precision/Reproducibility study, evaluates the device's ability to detect hCG at various concentrations independently. The results obtained by technicians also represent the device's standalone performance, albeit with trained human operation. The "Lay User Studies" also assess the device's performance when used by the intended end-user, essentially as a standalone OTC product.

7. Type of Ground Truth Used

Analytical Performance (Precision/Reproducibility, Spiked Standard Studies): Laboratory-prepared hCG spiked urine standards (known concentrations of hCG).
Method Comparison with Predicate Device: Clinical status (pregnant/not pregnant) of urine samples and comparison with a legally marketed predicate device.
Early Pregnancy Detection (Clinical Samples): Days relative to the missed period (biological/clinical stages of pregnancy).
Lay User Study: Clinical pregnancy status of the volunteers and technician-performed test results.
Specificity Study: Clinical status (non-pregnant) of women from different age cohorts.

8. Sample Size for the Training Set

The document describes performance studies for analytical and clinical validation. It does not provide information about a "training set" in the context of machine learning or AI development. This device is a chromatographic immunoassay, not an AI/ML-based device that typically requires a distinctive training set.

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

As noted above, the device is not an AI/ML-based device, so the concept of a "training set" and associated ground truth establishment is not applicable in this context. The various studies used laboratory standards or clinical status as their ground truth for evaluation.

Summary

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August 13, 2021

SPD Swiss Precision Diagnostics GmbH % Kamila Przedmojska Senior Regulatory Affairs Specialist SPD Development Company Limited Priory Business Park Bedford MK44 3UP United Kingdom

Re: K200913

Trade/Device Name: Clearblue® Early Digital Pregnancy Test Regulation Number: 21 CFR 862.1155 Regulation Name: Human Chorionic Gonadotropin (HCG) Test System Regulatory Class: Class II Product Code: LCX Dated: November 4, 2020 Received: November 6, 2020

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.

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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) 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 (QS) 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 medical devices and radiation-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,

Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health 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) K200913

Device Name Clearblue® Early Digital Pregnancy Test

Indications for Use (Describe)

The test is intended for home use.

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

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510(k) Summary

A. Submitted By:	SPD Swiss Precision Diagnostics GmbH 47 Route de Saint-Georges Petit-Lancy CH-1213 Geneva Switzerland Telephone: +41 580048741
B. Contact Person:	Kamila Przedmojska Senior Regulatory Affairs Specialist SPD Development Company Limited Priory Business Park Bedford MK44 3UP United Kingdom Telephone: +44 1234835504
C. Date Prepared:	11 August, 2021
D. Device Name:	Clearblue® Early Digital 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:	K123567, FIRST RESPONSE™ Gold Digital Pregnancy Test (K123567)

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F. Indication for Use

The test is intended for home use.

G. Device Description

H. Substantial Equivalence Information

Predicate device name: FIRST RESPONSE™ Gold Digital Pregnancy Test

Predicate (k) number: K123567

Comparison with predicate:

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

Component	Clearblue® Early DigitalPregnancy(Proposed Device)	FIRST RESPONSE™ GoldDigital Pregnancy Test(Predicate Device)
Similarities
IntendedUse	Qualitative detection ofhuman hCG for an aid inearly detection of pregnancy	Same
Component	Clearblue® Early DigitalPregnancy(Proposed Device)	FIRST RESPONSE™ GoldDigital Pregnancy Test(Predicate Device)
Target User	Over-The-Counter use	Same
Deviceformat	Single Use	Same
SampleMatrix	Urine	Same
Analyte	hCG	Same
hCGSensitivity	10mIU/ml	Same
Traceability	WHO 4th InternationalStandard for hCG	Same
TestPrinciple	Lateral flow qualitativechromatographicimmunoassay with digitalresult display	Same
Electroniccomponents	Microprocessor with specificcircuitry and algorithm. LCDreadout with battery aspower source.	Same
Sampleapplication	In-stream and dip methods	Same
Early Claim	Pregnancy can be detectedas early as six days beforethe date of the missedperiod (five days beforeexpected period).	Same
	Differences
hCGIsoformsDetected	Intact hCG	Intact hCGHyperglycosylated hCGhCG β-subunithCG β-core fragment
Samplingtime	The user is instructed toremove the absorbent tipfrom the urine when theStop Light begins to flash(usually 5 seconds for bothsampling methods)	5 seconds for both samplingmethods
Component	Clearblue® Early DigitalPregnancy(Proposed Device)	FIRST RESPONSE™ GoldDigital Pregnancy Test(Predicate Device)
Time toresults	1 -5 minutes	3 minutes
ResultDisplay	Pregnant / Not Pregnantdisplayed in words	YES+ (for Pregnant results)NO- (for Not Pregnant result)

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I. Test Principle

The Clearblue® Early Digital 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 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 until the Stop Light begins to flash (which usually takes 5 seconds for both sampling methods). Once the device self-calibration process is completed, a progress bar symbol appears on the display, indicating that test is working and counting down the time to result. The test is complete after a result (Pregnant/ Not Pregnant in words) or an error (book symbol) is displayed on the LCD. This occurs within 1-5 minutes of sample detection.

J. Performance characteristics

1. Analytical Performance

a) Precision/Reproducibility

A pooled negative urine was spiked with hCG to provide nine urine standards with the hCG concentrations of 0, 3, 4.5, 6, 7.5, 9, 10, 12.5 and 25 mIU/ml. The nine standards were each tested with devices from three different batches using both dip and simulated in-stream sampling methods.

The study was performed by three technicians over three non-consecutive days. On each test day, 3 technicians tested 5 devices each per batch, per standards, per sampling method.

The results demonstrate that the analytical sensitivity of the Clearblue® Early Digital Pregnancy Test device is 10mIU/ml. The analytical cut-off

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value (approximately half of the devices yield positive results and the remainder yield negative) has been determined as 7.6 mIU/ml.

The results are summarised in the tables below:

Overall Precision Results of Clearblue® Early Digital Pregnancy Test

hCGStandard(mIU/ml)	TotalSamples(n)	Clearblue® Early Digital Pregnancy Test Overall Results						TotalPregnant(%)
		Dip method			Simulated in stream method
		NotPregnant(n)	Pregnant(n)	PregnantResults(%)	NotPregnant(n)	Pregnant(n)	PregnantResults(%)
0	324	162	0	0.0	162	0	0.0	0.0
3	324	162	0	0.0	162	0	0.0	0.0
4.5	324	159	3	1.9	155	7	4.3	3.1
6	324	147	15	9.3	141	21	13.0	11.1
7.5	324	106	56	34.6	88	74	45.7	40.1
9	324	21	141	87.0	15	147	90.7	88.9
10	324	0	162	100.0	0	162	100.0	100.0
12.5	324	0	162	100.0	0	162	100.0	100.0
25	324	0	162	100.0	0	162	100.0	100.0

Percentage Pregnant Results for Each hCG Standard by Technician

hCGStandard(mIU/ml)	Technician 1		Technician 2		Technician 3
	P/NP*(n)	PregnantResults(%)	P/NP*(n)	PregnantResults(%)	P/NP*(n)	PregnantResults(%)
0	0/108	0.0	0/108	0.0	0/108	0.0
3	0/108	0.0	0/108	0.0	0/108	0.0
4.5	1/107	0.9	5/103	4.6	4/104	3.7
6	11/97	10.2	12/96	11.1	13/95	12.0
7.5	37/71	34.3	49/59	45.4	44/64	40.7
9	97/11	89.8	95/13	88.0	96/12	88.9
10	108/0	100.0	108/0	100.0	108/0	100.0
12.5	108/0	100.0	108/0	100.0	108/0	100.0
25	108/0	100.0	108/0	100.0	108/0	100.0

*Pregnant/Not Pregnant Results

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HcgStandard(Miu/ml)	Day 1		Day 2		Day 3
	P/NP*(n)	PregnantResults(%)	P/NP*(n)	PregnantResults(%)	P/NP*(n)	PregnantResults(%)
0	0/108	0.0	0/108	0.0	0/108	0.0
3	0/108	0.0	0/108	0.0	0/108	0.0
4.5	2/106	1.9	3/105	2.8	5/103	4.6
6	14/94	13.0	7/101	6.5	15/93	13.9
7.5	37/71	34.3	45/63	41.7	48/60	44.4
9	96/12	88.9	95/13	88.0	97/11	89.8
10	108/0	100.0	108/0	100.0	108/0	100.0
12.5	108/0	100.0	108/0	100.0	108/0	100.0
25	108/0	100.0	108/0	100.0	108/0	100.0

Percentage Pregnant Results for each hCG standard by Day

*Pregnant/Not Pregnant Results

	NEN0008/1R		NEN0008/2R		NEN0008/3
hCGStandard(mIU /ml)	P/NP*(n)	PregnantResults(%)	P/NP*(n)	PregnantResults(%)	P/NP*(n)	PregnantResults(%)
0	0/108	0.0	0/108	0.0	0/108	0.0
3	0/108	0.0	0/108	0.0	0/108	0.0
4.5	3/105	2.8	5/103	4.6	2/106	1.9
6	15/93	13.9	11/97	10.2	10/98	9.3
7.5	53/55	49.1	38/70	35.2	39/69	36.1
9	97/11	89.8	98/10	90.7	93/15	86.1
10	108/0	100.0	108/0	100.0	108/0	100.0
12.5	108/0	100.0	108/0	100.0	108/0	100.0
25	108/0	100.0	108/0	100.0	108/0	100.0

*Pregnant/Not Pregnant Results

b) Linearity/assay reportable range:

Not applicable. This is a qualitative device.

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c) High dose hook effect study:

Negative pooled urine was spiked with hCG to concentrations of <0.5, 10 and 1,000,000mIU/ml and tested with 5 replicates per each of three batches. No hook effect was observed at tested concentration.

d) Traceability

The tests are calibrated against the WHO 4th International Standards for 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

Structure not-related compounds

Interfering substances

The Clearblue® Early Detection Pregnancy Test devices were tested with potentially interfering substances. Each interfering substance was spiked into non-pregnant pooled urine and 10mIU/ml hCG urine standards.

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

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

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Structure related compounds

The Clearblue® Early Digital Pregnancy Test devices were tested with 3 potential cross reactants. Each potential cross reactant was spiked into non-pregnant pooled urine and 10mIU/ml hCG urine standard at the following concentration:

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Cross Reactant	Concentration
Follicle – StimulatingHormone (FSH)	1000 mIU/ml
Luteinizing Hormone (LH)	500 mIU/ml
Thyroid – StimulatingHormone (TSH)	1mIU/ml

No cross reactivity was observed at tested concentration.

Effects of urine pH

Effect of urine pH was performed by adjusting negative and 10mIU/ml hCG urine standard to a pH range of 4, 6 and 9. Each urine standard was tested with 34 devices from each of 3 batches by dip sampling method. The results demonstrated that Clearblue® Early Digital 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 urine specific gravity, device was challenged with negative (<0.5 mIU/ml hCG) and positive (10mIU/ml hCG) urine standards with the specific gravity of 1.000, 1.007, 1.014, 1.027 and 1.035. The results showed Clearblue® Early Digital 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 the hCGβcf, a total of 180 devices were tested:

Pooled pregnant urine from weeks 6-7 from LMP and negative . pooled urine spiked with hCG to a concentration representative of 6-7 weeks pregnant urine samples spiked with 1uM of hCGßcf
Pooled pregnant urine from weeks 9-12 from LMP and negative ● pooled urine spiked with hCG to a concentration representative of 9-12 weeks pregnant urine samples spiked with 1µM of hCGβcf
Non-pregnant pooled urine spiked to 10mIU/ml hCG and . 150pmol/L of hCGßcf
Positive (pooled pregnant urine without spiked hCGβcf) and ● negative (0mIU/ml) controls were also tested.

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Additionally, devices were tested with 30 individual clinical pregnant urine samples collected from late first trimester pregnancies selected as being those with the highest concentrations of hCGBcf.

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

h) Assay cut-off

See Precision/Reproducibility section.

1. Comparison Study
a. Method comparison with predicate device:

102 urine samples from pregnant women and 102 urine samples from not pregnant women were tested by trained technicians using the dipping and simulated in-stream method of sampling across three batches of Clearblue® Early Detection Pregnancy Test. The same samples were also tested using the predicate device FIRST RESPONSE™ Gold Digital Pregnancy Test, using the dip method of sampling.

Clearblue® Early Detection Pregnancy Test had 99.5% agreement with the FIRST RESPONSE™ Gold Digital Pregnancy Test and 100% agreement with the clinical status of the volunteers' urine samples.

b. Matrix comparison:

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

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)

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Detection of hCG in Early Pregnancy Clinical Samples

831 early pregnancy urine samples from days -1 to -10 relative to the day of the missed period were collected. Each sample was tested using both method of sampling across three batches of devices.

DaysRelativetoMissedPeriod	Dip Test results			Simulated In-stream TestResults			OverallPregnancyDetection
	NotPregnant(n)	Pregnant(n)	Pregnant(%)	NotPregnant(n)	Pregnant(n)	Pregnant(%)
-10	21	0	0.0	21	0	0.0	0.0
-9	36	0	0.0	36	0	0.0	0.0
-8	57	3	5.0	57	3	5.0	5.0
-7	67	35	34.3	62	40	39.2	36.8
-6	25	77	75.5	19	83	81.4	78.4
-5	7	95	93.1	7	95	93.1	93.1
-4	1	101	99.0	1	101	99.0	99.0
-3	0	102	100.0	0	102	100.0	100.0
-2	0	102	100.0	0	102	100.0	100.0
-1	0	102	100.0	0	102	100.0	100.0

The early pregnancy detection results are summarised in table below:

Lay User Study

Preqnant and not pregnant women volunteers with diverse educational and professional backgrounds and ages between 18 and 45 years old participated in the Lay User Study. They tested their own sample following both methods of sampling (if they wished to) according to the IFU provided.

The same urine sample was also tested by a technician by dip method only. Volunteer results were compared to their clinical pregnancy status and to the results obtained from trained technicians.

The study confirmed that PPV, NPV, sensitivity, specificity and accuracy for the Clearblue® Early Detection 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 (in-stream vs dip test) and their clinical status with the Clearblue® Early Detection Pregnancy Test

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was 100%. There was also 100% agreement between all lay-user volunteer results and technician dip results.

The results are summarised in tables below:

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

		Volunteer Result
		Not Pregnant	Pregnant	Total
Clinical Status	Not Pregnant	205	0	205
	Pregnant	0	189	189
	Total	205	189	394

Volunteer (In-stream) results and Technician (Dip) Results

	Volunteer In-Stream Result
	Not Pregnant	Pregnant	Total
TechnicianDip Result	Not Pregnant	101	0	101
	Pregnant	0	94	94
	Total	101	94	195

Volunteer and Technician Dip Sampling Method Device Results

	Volunteer Dip Result
	Not Pregnant	Pregnant	Total
TechnicianDip Result	Not Pregnant	104	0	104
	Pregnant	0	95	95
	Total	104	95	199

Specificity study to determine false-positive result rate

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A study was performed to determine the incidence of false positive results among non-pregnant women of pre-menopausal age (18-40 years), perimenopausal age (41-55 years) and post-menopausal age (>55 years). 150 urine samples were collected from individual women of each cohort. All 450 urine samples were tested by technicians with three batches of the Clearblue® Early Digital Pregnancy Test devices by dip method of sampling.

Cohort	Not Pregnant (n)	Samples (n)	Specificity (%)
Pre-menopausal	150	150	100.0
Peri-menopausal	150	150	100.0
Post-menopausal	149	150	99.3
All Not Pregnant	449	450	99.8

The results are summarised in table below:

There was 1 sample from the post-menopausal cohort with a raised hCG concentration that gave a positive result. The hCG concentration of this sample was determined as 7.83 mIU/ml, which is higher than the analytical cut-off of the device.

Lay User Spiked Standard Study

A study was performed to analyse the performance of the Clearblue® Early Digital Pregnancy Test, when read by lay users according to the Instruction for Use. A range of hCG urine standards at 3, 7.5, 8.5, 10 mIU/ml were tested by volunteers representing lay users by both dip and in-stream sampling method.

The overall results when tested by lay users are summarised in table below:

hCG standard(mIU/ml)	Total(n)	Pregnant(n)	Pregnant(%)
3	200	0	0
7.5	200	100	50
8.5	200	148	74
10	200	200	100

5. Clinical Cut-off

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Not applicable.

6. Expected value /Reference range

Not applicable.

Conclusion

The conclusions drawn from the nonclinical and clinical tests that demonstrate that the device is as safe, as effective, and performs as well as or better than the legally marketed predicate device: FIRST RESPONSE™ Gold Digital Pregnancy Test (K123567).

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.