lyn chen rongsheng technological zone, university …k181551 - lyn chen page 2 federal regulations,...

U.S. Food & Drug Administration 10903 New Hampshire Avenue D o c I D # 0 4 0 1 7 . 0 3 . 0 5 Silver Spring, MD 20993 www.fda.gov

February 22, 2019 Runbio BioTech Co.,Ltd Lyn Chen Official Correspondent Rongsheng Technological Zone, University Road Shantou, Guangdong 515063, China Re: k181551

Trade/Device Name: DAVID One Step Home Use Pregnancy Test Strip DAVID One Step Home Use Pregnancy Test Midstream DAVID One Step Home Use Pregnancy Test Cassette DAVID One Step Prescription Pregnancy Test Strip DAVID One Step Prescription Pregnancy Test Cassette

Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: Class II Product Codes: LCX, JHI Dated: January 8, 2019 Received: January 10, 2019

Dear Lyn Chen: 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

K181551 - Lyn Chen

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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (seehttps://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); goodmanufacturing 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, ifapplicable, 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 Part803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

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/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email ([email protected]) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Courtney H. Lias, Ph.D.DirectorDivision of Chemistry and Toxicology DevicesOffice of In Vitro Diagnostics

and Radiological HealthCenter for Devices and Radiological Health

Enclosure

Kellie B. Kelm -S

FORM FDA 3881 (7/17) Page 1 of 1 PSC Publishing Services (301) 443-6740 EF

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120Expiration Date: 06/30/2020See PRA Statement below.

510(k) Number (if known)K181551

Device NameDAVID One Step Prescription Pregnancy Test Strip

Indications for Use (Describe) DAVID One Step Prescription Pregnancy Test Strip is an in-Vitro diagnostic test device for the qualitative detection of human chorionic gonadotropin (HCG) in the urine. The test device is intended for use as an aid in early detection of pregnancy, in some cases as early as five (5) days before the expected period, i.e., as early as six (6) days before the day of the missed period. This product is intended for prescription 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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human ServicesFood and Drug AdministrationOffice of Chief Information OfficerPaperwork Reduction Act (PRA) [email protected]

“An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number.”



Indications for Use



Device NameDAVID One Step Prescription Pregnancy Test Cassette

Indications for Use (Describe) DAVID One Step Prescription Pregnancy Test Cassette is an in-Vitro diagnostic test device for the qualitative detection of human chorionic gonadotropin (HCG) in the urine. The test device is intended for use as an aid in early detection of pregnancy, in some cases as early as five (5) days before the expected period, i.e., as early as six (6) days before the day of the missed period. This product is intended for prescription use.










Indications for Use



Device NameDAVID One Step Home Use Pregnancy Test Strip

Indications for Use (Describe) DAVID One Step Home Use Pregnancy Test Strip is an in-Vitro diagnostic test device for the qualitative detection of human chorionic gonadotropin (HCG) in the urine. The test device is intended for use as an aid in early detection of pregnancy, in some cases as early as five (5) days before the expected period, i.e., as early as six (6) days before the day of the missed period. This product is intended for over-the-counter use.










Indications for Use



Device NameDAVID One Step Home Use Pregnancy Test Midstream

Indications for Use (Describe) DAVID One Step Home Use Pregnancy Test Midstream is an in-Vitro diagnostic test device for the qualitative detection of human chorionic gonadotropin (HCG) in the urine. The test device is intended for use as an aid in early detection of pregnancy, in some cases as early as five (5) days before the expected period, i.e., as early as six (6) days before the day of the missed period. This product is intended for over-the-counter use only.










Indications for Use



Device NameDAVID One Step Home Use Pregnancy Test Cassette

Indications for Use (Describe) DAVID One Step Home Use Pregnancy Test Cassette is an in-Vitro diagnostic test device for the qualitative detection of human chorionic gonadotropin (HCG) in the urine. The test device is intended for use as an aid in early detection of pregnancy, in some cases as early as five (5) days before the expected period, i.e., as early as six (6) days before the day of the missed period. This product is intended for over-the-counter use.








510(k) SUMMARY

The Assigned 510(k) number is K181551.

DATE of Summary: December 29，2018

A. Applicant

1.Company Name: RUNBIO BIOTECH CO., LTD

2.Address: RONGSHENG TECHNOLOGICAL ZONE,UNIVERSITY ROAD

SHANTOU, GUANGDONG, CHINA 515063

3.Telephone No.: 86-754-88116918

4.Fax: 86-754-88116915

B. Contact Information

1.Contact Person: LYN CHEN

2.Company Name: RUNBIO BIOTECH CO.,LTD

3.Address: RONGSHENG TECHNOLOGICAL ZONE,UNIVERSITY ROAD

SHANTOU, GUANGDONG, P.R.CHINA 515063

4.Telephone No.: 86-754-82758965

5.Fax No.: 86-754-88116915

6.E-mail Address:[email protected]

C. Proprietary and Established Names

DAVID One Step Home Use Pregnancy Test Strip

DAVID One Step Home Use Pregnancy Test Cassette

DAVID One Step Home Use Pregnancy Test Midstream

DAVID One Step Prescription Pregnancy Test Strip

DAVID One Step Prescription Pregnancy Test Cassette

D. Regulatory Information

1.Regulation section:

21 CFR 862.1155 Human Chorionic Gonadotropin (HCG) test system

2.Classification:

Class II

1

3.Product Code:

LCX: Kit, test, pregnancy, hCG, over the counter

JHI: visual, pregnancy，hcg, prescription use

4.Panel:

Chemistry (75)

E.Intended Use/Indication(s) for use

1.Intended Use:

See Indications for use below.

2.Indications for use:

DAVID One Step Home Use Pregnancy Test Strip is an in-Vitro diagnostic test

device for the qualitative detection of human chorionic gonadotropin (HCG) in the

urine. The test device is intended for use as an aid in early detection of pregnancy,

in some cases as early as five (5) days before the expected period, i.e., as early as

six (6) days before the day of the missed period.

This product is intended for over-the-counter use.

DAVID One Step Home Use Pregnancy Test Cassette is an in-Vitro diagnostic test





This product is intended for over-the-counter use.

DAVID One Step Home Use Pregnancy Test Midstream is an in-Vitro diagnostic

test device for the qualitative detection of human chorionic gonadotropin (HCG) in

the urine. The test device is intended for use as an aid in early detection of

pregnancy, in some cases as early as five (5) days before the expected period, i.e.,

as early as six (6) days before the day of the missed period.

This product is intended for over-the-counter use only.

2

DAVID One Step Prescription Pregnancy Test Strip is an in-Vitro diagnostic test





This product is intended for prescription use.

DAVID One Step Prescription Pregnancy Test Cassette is an in-Vitro diagnostic

test device for the qualitative detection of human chorionic gonadotropin (HCG) in

the urine. The test device is intended for use as an aid in early detection of

pregnancy, in some cases as early as five (5) days before the expected period, i.e.,

as early as six (6) days before the day of the missed period.

This product is intended for prescription use.

3. Special conditions for use statement(s):

DAVID One Step Home Use Pregnancy Test Strip is intended for over-the-counter

use.

DAVID One Step Home Use Pregnancy Test Cassette is intended for over-the-counter use.

DAVID One Step Home Use Pregnancy Test Midstream is intended for over-the-counter use.

DAVID One Step Prescription Pregnancy Test Strip is intended for prescription

use.

DAVID One Step Prescription Pregnancy Test Cassette is intended for prescription

use.

4. Special instrument requirements:

None

3

F. Device Description:

DAVID One Step Pregnancy Test is designed in three formats: strip, cassette, and

midstream. Each of the devices (strip, cassette and midstream) contains a pouch with

the test device and instructions for use, additional test cassette also contains a

disposable plastic dropper. The test cassette and test midstream consist of a

chromatographic test strip enclosed in plastic housing. The test strip contains mouse

monoclonal anti-β-hCG antibody, mouse monoclonal anti-α-hCG antibody, goat

anti-mouse IgG polyclonal antibody and colloidal gold.

The added plastic housing does not affect the performance of the product, which is

determined by the test strip. The only difference between the different formats is test

procedure.

The test uses two lines to indicate results. The appearance of two color bands, one at

the “Test line” and one at the “Control line” region means the test is “positive”. The

appearance of a color band at the “Control line” region but not at the “Test line”

region means the test is “negative”. If there are no colored bands in the “Control

line” area and “Test line” region or if there is no color band in “Control line” region

even there is a band in the “Test line” region; this means “invalid” test result.

G. Substantial Equivalence Information

1.Predicate Device Name(s)：

Church & Dwight Co., Inc., FIRST RESPONSE Early Result Pregnancy Test

2.Predicate 510（K）Number(s):

k123436

3. Comparison with predicate

Similarities Item Proposed Device Predicate device

Product Name DAVID One Step Pregnancy Test FIRST RESPONSE Early Result Pregnancy Test

Intended Use aid in early detection of pregnancy Same

Early Detection claim

Detects pregnancy as early as 5 days before the expected period or as early as 6 days before the

day of the missed period. Same

Results Qualitative Same Test Principle Sandwich Immunochromatographic Assay Same

Analytical Sensitivity 10mIU/mL Same

4

Differences Item Proposed Device Predicate device

Product Name DAVID One Step Pregnancy Test FIRST RESPONSE

Early Result Pregnancy Test

Device format Strip, Cassette, Midstream Midstream

Intended User Prescription use (strip and cassette) and OTC use (strip, cassette and midstream) OTC Use

Time to Result 5 minutes 3 minutes

Specificity LH at 500 mIU/mL, FSH at 1000 mIU/mL, and TSH at 1000 μIU/mL

hLH and hFSH at 1000 mIU/mL, hTSH

at 1 mIU/mL

High Dosage Hook effect

No high dosage hook effect for hCG up to 2000,000 mIU/mL

No high dosage hook effect for hCG up to

500 IU/mL.

Traceability WHO International Standard 5th WHO Chorionic Gonadotrophin

WHO 4th International

Standard for hCG

H. Guidance Document:

None were referenced

I. Test Principle:

The test is a qualitative, solid phase, double antibodies sandwich

immunochromatographic assay.

During the test, hCG in the urine specimen reacts with the dye conjugate (mouse

anti-β-hCG antibody- colloidal gold conjugate specific to the beta subunit of hCG)

and forms a complex. The complex migrates along the membrane to the mouse

anti-α-hCG antibody test region (T), and remains captured in the T line.

J．Performance Characteristics:

1. Analytical performance

a. Precision/Reproducibility

Dilute HCG standard with negative urine samples from healthy women to different

concentrations: HCG0mIU/mL, HCG 3mIU/mL, HCG 6mIU/mL,

HCG7.5mIU/mL, HCG9mIU/mL, HCG 10mIU/mL, HCG15mIU/mL and

HCG25mIU/mL.

5

In each site of the 3 sites, one format of reagent will be used for detection by 1

investigator. In each day of test, 10pcs of reagents from each lot, totally 3 lots, will

be used for detection. Test will be conducted every other day, totally 5 days.

Table: statistics of test results by strips

hCG Concentration LOT1 LOT2 LOT3 % positive

HCG0mIU/mL -/-(50/50) -/-(50/50) -/-(50/50) 0%

HCG 3mIU/mL -/-(50/50) -/-(50/50) -/-(50/50) 0%

HCG 6mIU/mL -/-(49/50) -/-(49/50) -/-(50/50) 1%

HCG 7.5mIU/mL +/+(26/50) +/+(24/50) +/+(24/50) 49%

HCG 9mIU/mL +/+(49/50) +/+(49/50) +/+(48/50) 97%

HCG 10mIU/mL +/+(50/50) +/+(50/50) +/+(50/50) 100%

HCG 15mIU/mL +/+(50/50) +/+(50/50) +/+(50/50) 100%

HCG 25mIU/mL +/+(50/50) +/+(50/50) +/+(50/50) 100%

Table: statistics of test results by cassettes


HCG0mIU/mL -/-(50/50) -/-(50/50) -/-(50/50) 0%

HCG 3mIU/mL -/-(50/50) -/-(50/50) -/-(50/50) 0%

HCG 6mIU/mL -/-(49/50) -/-(49/50) -/-(49/50) 2%

HCG 7.5mIU/mL +/+(25/50) +/+(26/50) +/+(24/50) 50%

HCG 9mIU/mL +/+(49/50) +/+(50/50) +/+(49/50) 98%

HCG 10mIU/mL +/+(50/50) +/+(50/50) +/+(50/50) 100%

HCG 15mIU/mL +/+(50/50) +/+(50/50) +/+(50/50) 100%

HCG 25mIU/mL +/+(50/50) +/+(50/50) +/+(50/50) 100%

6

Table: statistics of test results by midstreams


HCG0mIU/mL -/-(50/50) -/-(50/50) -/-(50/50) 0%

HCG 3mIU/mL -/-(50/50) -/-(50/50) -/-(50/50) 0%

HCG 6mIU/mL -/-(50/50) -/-(50/50) -/-(50/50) 0%

HCG 7.5mIU/mL +/+(24/50) +/+(24/50) +/+(24/50) 48%

HCG 9mIU/mL +/+(47/50) +/+(48/50) +/+(47/50) 95%

HCG 10mIU/mL +/+(50/50) +/+(50/50) +/+(50/50) 100%

HCG 15mIU/mL +/+(50/50) +/+(50/50) +/+(50/50) 100%

HCG 25mIU/mL +/+(50/50) +/+(50/50) +/+(50/50) 100%

b. Linearity/assay reportable range:

Linearity is not applicable since this is a qualitative test.

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

Traceability:

The tests is calibrated against the WHO International Standard 5th WHO

Chorionic Gonadotrophin （NIBSC code: 07/364）

Stability:

The stability testing protocol and acceptance criteria used to support the shelf

life were reviewed and found to be acceptable. The sponsor claims a 30-month

shelf life for all three test formats when stored in the sealed foil pouch at

36-86ºF (2-30ºC).

Expected values :

1. Negative results are expected in healthy non-pregnant women.

2. The amount of hCG will vary greatly with gestational age and between

individuals.

d. Detection limit:

Select 30 healthy non-pregnant women and collect their urine samples as basic

diluted urine. Separate each sample into 10 sets respectively, each of which is

spiked with HCG standard to get required concentrations, respectively are ：

HCG0mIU/mL, HCG3mIU/mL, HCG 5mIU/mL, HCG6mIU/mL ,

HCG7.5mIU/mL, HCG9mIU/mL, HCG 10mIU/mL, HCG12.5mIU/mL ,

7

HCG15mIU/mL and HCG25mIU/mL. There are 30 samples for each

concentration. All the samples are re-numbered and divided into 4 sets，so each

group of samples have 10 different concentrations and each concentration is

made with negative urine sample from 30 different women. All the samples are

stored below -20 ℃.

There were 3 formats of reagent for assessment: strip, cassette and midstream.

There were two test methods for the midstream format: the dip method and the

simulated stream method. For each format, 3 lots of reagents would be used for

test.

12 laboratory operators were selected to carry out this test based on different test

methods. The 12 operators would be separated into 4 groups, 3 for each group,

and then respectively test with strips, cassettes , midstreams (the dip method) and

midstreams (the simulated stream method). Table: Summary of Test Results by Strips

hCG concentration LOT1 LOT2 LOT2 % positive HCG0mIU/mL +/+(0/30) +/+(0/30) +/+(0/30) 0% HCG 3mIU/mL +/+(/30) +/+(0/30) +/+(1/30) 1% HCG5mIU/mL +/+(1/30) +/+(0/30) +/+(0/30) 1% HCG 6mIU/mL +/+(1/30) +/+(2/30) +/+(1/30) 3%

HCG 7.5mIU/mL +/+(15/30) +/+(15/30) +/+(14/30) 48% HCG 9mIU/mL +/+(30/30) +/+(29/30) +/+(29/30) 98% HCG 10mIU/mL +/+(30/30) +/+(30/30) +/+(30/30) 100% HCG13mIU/mL +/+(30/30) +/+(30/30) +/+(30/30) 100% HCG 15mIU/mL +/+(30/30) +/+(30/30) +/+(30/30) 100% HCG 25mIU/mL +/+(30/30) +/+(30/30) +/+(30/30) 100%

Table: Summary of Test Results by Cassettes

hCG concentration LOT1 LOT2 LOT2 % positive HCG0mIU/mL +/+(0/30) +/+(0/30) +/+(0/30) 0% HCG 3mIU/mL +/+(0/30) +/+(1/30) +/+(0/30) 1% HCG5mIU/mL +/+(1/30) +/+(0/30) +/+(1/30) 2% HCG 6mIU/mL +/+(2/30) +/+(1/30) +/+(1/30) 4%


8

Table: Summary of Test Results by Midstreams (the dip method)



Table: Summary of Test Results by Midstreams (the simulated stream method)



The results demonstrated that the analytical sensitivity of the new device (the

lowest concentration that yields 100% positive results) was 10mIU/mL and the

cut-off level (at which approximately half of the devices yield positive results and

the remainder yield negative results) was 7.5 mIU/mL.

e. Analytical specificity:

Cross reactivity:

To evaluate cross-reactivity, 20 fresh urine specimens obtained from 10 healthy

non-pregnant women and 10 healthy men 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

(10mIU/ml) samples. The results demonstrated no cross reaction with LH at

500mIU/ml, FSH at 1000 mIU/mL, and TSH at 1000μIU/mL.

9

Interference:

A study was conducted to evaluate interference of specific exogenous compounds.

Negative and positive hCG urine samples (10 mIU/mL) were individually spiked

with the substances listed in the table below. Three devices of each format were

tested. No interference was observed from the compounds at the concentrations

listed below. Table: potential endogenous substances

Name Concentration Name Concentration Glucose 20mg/mL Bilirubin 20μg/mL Albumin 20mg/mL estriol 10μg/mL

Hemoglobin 10μg/mL

Table common birth control pills and progestational drugs

Name Concentration Name Concentration

Levonorgestrel 11.8mg/mL Ethynylestradiol cyproterone 2mg/mL

Bromocriptine mesylate 2.5mg/mL Progesterone 100mg/mL

Clomiphene citrate 50mg/mL Medroxyprogesterone acetate 2mg/mL

Letrozole 2.5mg/mL Ethinylestradiol 13.8mg/mL

Estradiol 13.6mg/mL

Table: prescription and OTC use exogenous substances

Name Concentration Name Concentration

Acetaminophen 200μg/mL Phenothiazine 200μg/mL Acetylsalicylic Acid 200μg/mL Phenylpropanolamine 200μg/mL

Ascorbic Acid 200μg/mL Tetracycline 200μg/mL Ampicillin 200μg/mL Ephedrine 200μg/mL Atropine 200μg/mL Aspirin 200μg/mL Caffeine 200μg/mL Thiophene 200μg/mL

Gentisic Acid 200μg/mL Salicyclic Acid 200μg/mL Ethanol 1%

10

Table: antibiotic Name Concentration Name Concentration

Amikacin 15 mg/dL Kanamycin A 10 mg/dL Amphotericin B 10μg/mL Kanamycin B 10mg/dL

Cefdinir 100μg/mL Penicillian G 100g/mL Cefuroxime 100μg/mL Rifampin 5mg/dL Cephradine 100μg/mL Spectinomycin 100μg/mL Ciprofloxin 10μg/mL Tobramycin 2mg/dL Gentamicin 15mg/dL Vancomycin 6mg/dL

Effects of Urine pH：

A study was conducted to evaluate the effect of pH. Negative and positive hCG

urine samples (10 mIU/mL) were tested across a pH range of 4-9. The results

demonstrate that pH ranging from 4 to 9 in urine samples does not interfere with

the performance of the test.

Specific Gravity:

A study was performed to evaluate the effects of urine specific gravity on the

device. The device was challenged with negative urine and positive urine with

specific gravity from 1.000 to 1.050. The results demonstrate that specific gravity

ranging from 1.000 to 1.050 in urine samples does not interfere with the

performance of the test.

High dose hook effect study:

The test was evaluated for high dose hook effect. Negative urine specimens were

spiked with high hCG concentration of up to 2000,000 mIU/mL. All samples

yielded the expected results. This study demonstrates that this device shows no

hook effect up to 2,000,000 mIU/mL hCG.

Effects of hCG β-core Fragment:

Interference testing was performed to evaluate whether high levels of beta core

fragment interfere with the device. Negative urine hCG and positive urine samples

(containing 10 mIU/mL hCG) were spiked with hCG beta core fragment at

concentrations of62,500, 125,000, 250,000, 500,000, and 1,000,000 pmol/L.

Concentrations of hCG beta core fragment up to 1,000,000 pmol/L yielded correct

11

results. Interference from hCG β-core fragment was demonstrated at

concentrations of 1,000,000 pmol/L.

2. Comparison Study:

a. Method comparison with predicate device:

Tests were conducted at 3 different sites. In each site, 120 urine samples were

simultaneously double-blind tested by professionals using both predicate devices

and one format of proposed devices. Simultaneously, two test methods of

midstream, the dip method and the simulated stream method, would be compared.

Table: statistic analysis of data of strips

Predicate Device

Positive Negative total

Proposed

Device

Positive (a)52 (b)0 (a＋b)52

Negative (c)0 (d)68 (c＋d)68

total (a＋c)52 (b＋d)68 (a+b+c+d)120

Table: statistic analysis of data of cassettes

Predicate Device


Proposed

Device



total (a＋c)64 (b＋d)56 (a+b+c+d)120

Table: statistic analysis of data of midstream (the dip method)

Predicate Device


Proposed

Device



total (a＋c)73 (b＋d)47 (a+b+c+d)120

12

Table: statistic analysis of data of midstream

the dip method by proposed device


the simulated stream method by

proposed device



total (a＋c)73 (b＋d)47 (a+b+c+d)120

b. Matrix comparison:

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

3. 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

A total of 1287 urine samples were collected from 99 different women (20-40 years

old) who planned to become pregnant. These women were followed throughout

their conception cycles with urine collected from day -10 to day 2 of their expected

period. These 1287 samples were then tested by laboratory technicians (one for

strip, one for cassette format, and one for midstream for both dip and stream

methods). Urine samples were masked and randomized by people who prepared

samples but did not participate in the testing. One lot of each test device was used.

At last, confirm all positive samples with ultrasound scan.

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Table: results by strip Day relative

to EMP Overall Pregnancy Detection Rate (%)

Number of positive samples

Number of negative samples

Day in cycle relative to EMP

+2 100% 99 0 EMP+2 +1 100% 99 0 EMP+1 0 100% 99 0 EMP -1 100% 99 0 EMP-1 -2 99% 98 1 EMP-2 -3 99% 98 1 EMP-3 -4 96% 95 4 EMP-4 -5 78% 77 22 EMP-5 -6 38%. 38 61 EMP-6 -7 17% 17 82 EMP-7 -8 7% 7 92 EMP-8 -9 3% 3 96 EMP-9 -10 0% 0 99 EMP-10

Table: results by cassette

Day relative to EMP

Overall Pregnancy Detection Rate (%)





Table: results by midstream (the dip method)

Day relative to EMP






14

Table: results by midstream (simulated stream method)

Day relative to EMP






Layuser study

This study was performed at 3 sites on Chinese mainland. Chose women

volunteers who had certain English reading ability and were willing to take time

to assist the site to complete the test without compensation. These volunteers should

have diverse educational and professional background but without corresponding medical

background and their age range were between 20 and 40 years old.

Each unit completed the selection of 120 volunteers to conduct this lay user study,

of which 50 were pregnant women and 70 were non-pregnant women.

Each site completed a study of a format, and the midstream format was used for

test by simulated stream method and dip method.

All volunteers, after reading the English manual of the corresponding format of

the product provided by the applicant, independently completed the collection,

detection and result judgment of their urine samples without the assistance of

professionals. The simultaneously collected urine samples by the volunteers

were detected by professionals after blinded (the people who blinded the

samples do not participate in the test). The test results of the professional and

non-professional were summarized as follows:

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Table: statistic analysis of data of strips

results by professionals Positive Negative total

Proposed Device results by

non-professionals



total (a＋c)50 (b＋d)70 (a+b+c+d)120

Table: statistic analysis of data of cassettes



non-professionals



total (a＋c)50 (b＋d)70 (a+b+c+d)120

Table: statistic analysis of data of midstreams



non-professionals



total (a＋c)50 (b＋d)70 (a+b+c+d)120

Table: statistic analysis of data of midstreams (non-professionals)

the dip method with proposed device Positive Negative total

the simulated stream method with

proposed device



total (a＋c)50 (b＋d)70 (a+b+c+d)120

The second study is conducted with diluted samples. 120 volunteers at each site detect 4 samples containing different concentration of HCG,

HCG 5mIU/mL, HCG 8mIU/mL, HCG 10mIU/mL and HCG11.5mIU/mL, after collection

of their own urine samples. The midstream format will be used for detection in

the dip method and the simulated stream method. The testing was performed at 3

intended use sites. One lot of each of the three test formats were used in the study.

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Table：Statistical table of test results of samples spiked with HCG（Strip）

concentration Test Sample Lay users Results

% positive Number of Positive

Number of Negative

HCG 5mUI/mL Sample 1 2 118 2% HCG 10mIU/mL Sample 2 120 0 100%

HCG 11.5mIU/mL Sample 3 120 0 100% HCG 8mIU/mL Sample 4 52 68 43%

Table：Statistical table of test results of samples spiked with HCG（Cassette）



Number of Negative



Table: Statistical table of test results of samples spiked with HCG（Midstream）



Number of Negative



The results show that when use the product to detect samples spiked with HCG at

concentrations which are above or below the detection limit (HCG10mIU/mL),

for samples whose HCG concentrations are 5mIU/mL, 1-2 of the test results is

positive, and for samples whose HCG concentrations are 10mIU/mL, all the

results are positive.

Because this test detects low levels of hCG, it is possible that this test may give

positive results even if you are not pregnant. If you test positive, but think you

may not be pregnant, you should check with your doctor.

360 volunteers who have finished the study with clinical samples were willing to

do a questionnaire survey. All the questions in the questionnaire were in Likert

scale style. At the same time, a Flesch-Kincaid reading analysis is performed on

each package insert and the score demonstrates a reading Grade Level of 8.The

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results of the questionnaire reflects that the consumers find the device easy to use

and that they do not have trouble understanding the labeling or interpreting

results.

Non-pregnant urine sample analysis :

A total of 900 samples were tested in three clinical trial sites by professionals. In

each unit, there were 100 samples for each age group, and one format of device

from 3 lots would be used for detection.

Table: statistics of test results

Age Group Test Result

Positive Negative pre-menopausal group

(18-40) +/+(0/300) -/-(300/300)

menopausal group (41-55)

+/+(0/300) -/-(300/300)

post menopausal group (> 55)

+/+(1/300) -/-(299/300)

As can be seen from the test results in the above table, 1 false positive result

occurred in non-pregnant women over 55 years old. The concentrations of these

samples were determined to be higher than the cut-off of the device by

quantitative test.

3.Clinical cut-off:

Not applicable

4. Expected values/Reference range:

Not applicable.

M. Proposed Labeling:

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

N. CONCLUSION:

The submitted information in this premarket notification is complete and supports

a substantial equivalence decision.

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