i-STAT Total beta-hCG Test, i-STAT Total beta-hCG Controls, i-STAT Total beta-hCG Calibration Verification Materials

K133002 · Abbott Point of Care, Inc. · DHA · Apr 16, 2015 · Clinical Chemistry

Device Facts

• Record ID: K133002
• Device Name: i-STAT Total beta-hCG Test, i-STAT Total beta-hCG Controls, i-STAT Total beta-hCG Calibration Verification Materials
• Applicant: Abbott Point of Care, Inc.
• Product Code: DHA · Clinical Chemistry
• Decision Date: Apr 16, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1155
• Device Class: Class 2

Intended Use

The i-STAT® Total Beta-Human Chorionic (B-hCG) test is an in vitro diagnostic test for the quantitative and qualitative determination of ß-hCG in venous whole blood or plasma samples using the i-STAT 1 Analyzer Systems. The test is intended to be used as an aid in the early detection of pregnancy and is for prescription use only. The i-STAT® Total B-hCG Controls are used to monitor performance of the i-STAT Total β-hCC test. The i-STAT® Total B-hCG Calibration Verification Materials are used to verify the calibration of the i-STAT Total BhCG test throughout the reportable range.

Device Story

The i-STAT Total ß-hCG test is a point-of-care diagnostic cartridge used with the i-STAT 1 Analyzer. It utilizes a two-site enzyme-linked immunoassay (ELISA) with electrochemical detection. Monoclonal antibodies specific to the ß-hCG subunit are localized on an electrochemical sensor chip; a reference sensor is included for signal normalization. During operation, the sample is introduced to the cartridge, where simultaneous capture and labeling occur using an alkaline phosphatase-linked monoclonal antibody. The analyzer measures the electrochemical signal generated by the enzyme-substrate reaction. Results are displayed to the clinician to aid in pregnancy detection. The system provides rapid quantitative results from whole blood or plasma, facilitating immediate clinical decision-making at the point of care.

Clinical Evidence

Bench testing only. Performance evaluated via precision (CLSI EP05-A2), linearity (CLSI EP06-A), interference (CLSI EP07-A2), and method comparison (CLSI EP09-A2) against predicate. Precision studies (N=75 per level) showed CVs ranging from 4.3% to 18.7%. Method comparison (N=134) showed high correlation (r=0.99) with predicate. No clinical sensitivity/specificity studies performed.

Technological Characteristics

Two-site enzyme-linked immunoassay (ELISA) on a disposable cartridge. Sensing principle: electrochemical detection of alkaline phosphatase-linked antibody signal. Sample: venous whole blood or plasma. Connectivity: i-STAT 1 Analyzer. Reportable range: 5.0–2000.0 IU/L. Controls/Calibration materials: assayed human serum.

Indications for Use

Indicated for quantitative and qualitative determination of β-hCG in venous whole blood or plasma to aid in early pregnancy detection. For prescription use only.

Regulatory Classification

Identification

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

Predicate Devices

• Abbott ARCHITECT® Total β-hCG assay (k983424)
• Cliniqa Beta HCG Control Level 1, 2, 3 (k121237)
• Cliniqa Beta HCG Calibration Verification Control Level 1, 2, 3 (k121237)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

April 16, 2015

ABBOTT POINT OF CARE, INC. MELISSA ROBINSON ASSOCIATE DIRECTOR OF REGULATORY AFFAIRS 400 COLLEGE ROAD EAST PRINCETON NJ 08540

Re: K133002 Trade/Device Name: i-STAT® Total B-hCG Test, i-STAT® Total β-hCG Controls, i-STAT® Total ß-hCG Calibration Verification Materials Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (hCG) test system Regulatory Class: II Product Code: DHA, JJX Dated: April 9, 2015 Received: April 13, 2015

Dear Ms. Robinson:

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. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Katherine Serrano -S

For : Courtney H. Lias, Ph.D.

Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) k133002

Device Name

i-STAT Total ß-hCG test i-STAT Total B-hCG Controls and i-STAT Total ß-hCG Calibration Verification Materials

### Indications for Use (Describe)

The i-STAT® Total Beta-Human Chorionic (B-hCG) test is an in vitro diagnostic test for the quantitative and qualitative determination of ß-hCG in venous whole blood or plasma samples using the i-STAT 1 Analyzer Systems. The test is intended to be used as an aid in the early detection of pregnancy and is for prescription use only.

The i-STAT® Total B-hCG Controls are used to monitor performance of the i-STAT Total β-hCC test.

The i-STAT® Total B-hCG Calibration Verification Materials are used to verify the calibration of the i-STAT Total BhCG test throughout the reportable range.

X 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/0 description: The image shows a blue logo of Abbott. The logo is a stylized letter 'a' with a rounded, sans-serif font. The 'a' is enclosed in a square shape, with the top and bottom lines of the square forming the top and bottom of the 'a'. The logo is simple and modern, and the blue color gives it a sense of trustworthiness and reliability.

# 510(k) Summary i-STAT Total ß-hCG Test

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1900 and CFR 807.92.

The assigned 510(k) number is: k133002

### Date Summary prepared:

#### 1. Submitted by:

Abbott Point of Care Inc. 400 College Road East Princeton, NJ 08540 Phone: [phone] FAX: [phone]

### Establishment Registration Number: 2245578

### Contact:

Melissa Robinson 400 College Road East Princeton, NJ 08540 Phone: [phone] Fax: [phone]

#### 2. Identification of the Device:

Device Classification Name: System, Test, Human Chorionic Gonadotropin Device Name: i-STAT Total ß-hCG Test Classification: Class II (regulation number 862.1155) Classification Product Code: DHA

Device Classification Name: Quality Control Material (Assayed and Unassayed) Device Name: i-STAT Total ß-hCG Control Level 1, 2, 3 Classification:Class I (regulation 862.1660) Product Code: JJX

Regulation Description: Quality Control Material (Assayed and Unassayed) Device Name: i-STAT Total ß-hCG Calibration Verification Levels 1, 2, 3 Classification:Class I (regulation 862.1660) Product Code: JJX

Image /page/3/Picture/16 description: The image shows the logo for Abbott. On the left is a blue symbol that resembles a lowercase "a". To the right of the symbol is the name "Abbott" in bold, black letters. Below the name is the phrase "A Promise for Life" in a smaller font.

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Image /page/4/Picture/0 description: The image shows the logo for Abbott, a healthcare company. The logo is a stylized letter "a" in a sans-serif font. The letter is a solid, light blue color. The logo is simple and modern, and it is easily recognizable.

#### 3. Predicate Device

Predicate Device Name: Abbott ARCHITECT System Total ß-hCG Predicate 510(k) Number: k983424 Regulation Number: Class II (regulation number 862.1155) Classification Product Code: DHA

Predicate Device Name: Cliniqa Beta HCG Control Level 1, 2, 3 Predicate 510(k) Number: k121237 Regulation Description: Quality Control Material (Assayed and Unassayed) Classification: Class 1 (regulation 862.1660) Product Code: JJX

Predicate Device Name: Cliniqa Beta HCG Calibration Verification Control Levels 1, 2, 3 Predicate 510(k) Number: k121237 Regulation Description: Quality Control Material (Assayed and Unassayed) Classification: Class 1 (regulation 862.1660) Product Code: JJX

#### 4. Intended Use/Indications for Use:

The i-STAT® Total Beta-Human Chorionic Gonadotropin (B-hCG) test is an in vitro diagnostic test for the quantitative and qualitative determination of ß-hCG in venous whole blood or plasma samples using i-STAT 1 Analyzer Systems. The test is intended to be used as an aid in the early detection of pregnancy and is for prescription use only.

i-STAT Total ß-hCG Controls are used to monitor the performance of the i-STAT Total ß-hCG test.

i-STAT Total B-hCG Calibration Verification materials are used to verify the calibration of the i-STAT Total B-hCG test throughout the reportable range.

#### 5. Device Description:

The i-STAT Total ß-hCG test uses a two-site enzyme-linked immunoassay with electrochemical detection of the resulting enzyme signal. Monoclonal antibodies specific for the ß subunit of hCG are localized within a lithographically defined capture region on the surface of a specially designed electrochemical sensor chip. A separate reference sensor of similar construction to the hCG sensor, but without antibodies specific to hCG, is located on the same sensor chip. An alkaline phosphatase-linked monoclonal antibody conjugate specific to a separate epitope on the ß subunit of the hCG molecule is present in a metered amount on the sensor chip.

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Image /page/5/Picture/0 description: The image shows the logo for Abbott, a healthcare company. The logo is a stylized letter 'a' in a solid blue color. The 'a' is designed with rounded corners and a modern, minimalist aesthetic. The logo is simple and recognizable, representing the company's brand identity.

The i-STAT Total ß-hCG Controls are assayed human serum which are used to monitor the performance of the i-STAT Total ß-hCG test.

The i-STAT Total ß-hCG Calibration Verification materials are assayed human serum used to verify the calibration of the i-STAT Total β-hCG test throughout the reportable range.

#### 6. Substantial Equivalence Information:

| Characteristic | Predicate Device<br>Abbott ARCHITECT | Proposed Device<br>APOC i-STAT System |
|-----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The ARCHITECT Total β-hCG<br>Assay is a Chemiluminescent<br>Microparticle Immunoassay<br>(CMIA) for the quantitative and<br>qualitative determination of beta-<br>human chorionic gonadotropin<br>(β-hCG) in human serum and<br>plasma for the early detection of<br>pregnancy. | The i-STAT® Total Beta-Human<br>Chorionic Gonadotropin (β-hCG)<br>test is an <i>in vitro</i> diagnostic test<br>for the quantitative and<br>qualitative determination of<br>βhCG in venous whole blood or<br>plasma samples. The test is<br>intended to be used as an aid in<br>the early detection of pregnancy |
| Assay<br>Methodology | Two site ELISA | Two site ELISA |
| Capture Site | Heterogenous | Heterogenous |
| Capture<br>Antibodies | Monoclonal | Monoclonal |
| Label Antibody | Monoclonal | Monoclonal |
| Label | Acridinium | Alkaline Phosphotase |
| Analysis<br>Sequence | Sequential capture/label | Simultaneous capture/label |
| Analysis Time | 15.6 minutes | 10 minutes |
| Sample Type | Serum or plasma | Whole blood or plasma |
| Enzyme<br>Detection | Chemiluminescent Microparticle<br>Immunoassay | Electrochemical |

### Comparison with predicate (i-STAT Total β-hCG Cartridge):

Image /page/5/Picture/8 description: The image shows the Abbott logo. The logo consists of a blue stylized letter "a" on the left and the word "Abbott" in bold, black font on the right. Below the word "Abbott" is the phrase "A Promise for Life" in a smaller, lighter font.

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Image /page/6/Picture/0 description: The image shows a blue logo of Abbott. The logo is a stylized letter 'a' with rounded corners. The 'a' is formed by a thick line that starts at the top left, curves down and to the right, then curves back up and to the left, forming a closed shape. The logo is simple and modern, and the blue color is clean and professional.

The table below describes the features of the i-STAT Total ß-hCG Cartridge and predicate device that are apparently different.

| <b>Analysis of Difference</b> | |
|-------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Detection | The ARCHITECT detects an optical signal from the acridinium label while the i-STAT System detects the enzyme label by reacting with a substrate so as to generate an electrochemically detectable product. |
| Label | Acridinium is a chemiluminescent label while alkaline phosphatase is an enzyme label. |
| Analysis Sequence | The ARCHITECT is an ELISA with sequential capture and labeling while the i-STAT System is a simultaneous ELISA with capture and label occurring in parallel. |
| Sample Type | The ARCHITECT accepts serum or plasma while the i-STAT device is intended for whole blood or plasma specimens. This submission includes a detailed analysis of equivalence between blood and plasma for the i-STAT Total β-hCG test (see section 18.2.4). This data supports the claim of equivalence between blood and plasma. |
| Reportable Range | The ARCHITECT reports from 1.20 IU/L to 225,000.00 IU/L; the i-STAT Total β-hCG test has a reportable range of 5.0 IU/L to 2000.0 IU/L. These devices are intended for the early detection of pregnancy, consistent with a β-hCG result above 25 IU/L1. The reportable ranges for these devices both exceed that necessary for this intended use. |

Image /page/6/Picture/6 description: The image shows the logo for Abbott. The logo consists of a blue stylized letter "a" on the left, followed by the word "Abbott" in bold, black letters. Below the word "Abbott" is the tagline "A Promise for Life" in a smaller, lighter font.

¹ Tietz NW, Clinical Guide to Laboratory Tests, 4th Ed. 2006. p. 2160-2161.

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Image /page/7/Picture/0 description: The image shows a blue logo of Abbott. The logo is a stylized letter 'a' with rounded corners. The logo is simple and modern, and it is likely used to represent the company in a variety of contexts.

# Comparison with predicate (i-STAT β-hCG Control and Calibration Verification Material):

| Characteristic | Predicate Device | Proposed Device |
|------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Cliniqa Beta HCG Control Level<br>1, 2, 3 and Cliniqa Beta HCG<br>Calibration Verification Controls<br>Level 1, 2, 3(k121237) | i-STAT Total β-hCG Controls<br>and Calibration Verification<br>Material |
| Intended Use | Cliniqa Beta HCG Control Level<br>1, Cliniqa Beta HCG Control<br>Level 2, Cliniqa Beta HCG<br>Control Level 3 are assayed<br>quality control material used to<br>monitor the precision Beta HCG<br>assays. | i-STAT Total β-hCG Controls<br>are used to monitor the<br>performance of the i-STAT<br>Total β-hCG test. |
| | Cliniqa Beta HCG Calibration<br>Verification Controls, level 1, 2,<br>and 3 are assayed quality control<br>materials used to monitor the<br>precision of Beta HCG assays. | i-STAT Total β-hCG<br>Calibration Verification<br>materials are used to verify the<br>calibration of the i-STAT Total<br>β-hCG test throughout the<br>reportable range. |
| Matrix | Human serum with added buffer<br>stabilizers, and purified human<br>hormones. | Human serum with added<br>buffer stabilizers, and purified<br>human hormones. |
| Form | Liquid | Liquid |
| Open Vial<br>Stability | 30 days | 30 days |
| Caution | Human Source Material | Human Source Material |
| Values | Specific for each lot | Specific for each lot |
| Stability | Opened: 30 days at 2-8 °C<br>Shelf Life: 3 years at 2-8 °C | Opened: 30 days at 2-8 °C<br>Shelf Life: 3 years at 2-8 °C |

Image /page/7/Picture/5 description: The image shows the logo for Abbott. The logo consists of a blue stylized "a" on the left, followed by the word "Abbott" in a bold, dark font. Below "Abbott" is the tagline "A Promise for Life" in a smaller, lighter font. The logo is clean and professional, conveying a sense of trust and reliability.

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### 7. Standard/Guidance Documents

CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods

CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07-A2: Interference Testing in Clinical Chemistry

CLSI EP09-A2: Method Comparison and Bias Estimation Using Patient Samples CLSI EP12-A2: User Protocol for Evaluation of Qualitative Test Performance CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures

CLSI C28-A3c: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory

CLSI I/LA30-A: Immunoassay Interference by Endogenous Antibodies ISO 14971: Medical Devices – Application of Risk Management to Medical Devices

### i-STAT Total ß-hCG Cartridge Performance Characteristics: 8.

# i-STAT Total ß-hCG test cartridge:

Blood to Plasma Equivalence a)

The i-STAT Total B-hCG test is designed to function using whole blood or plasma at the point of care. To support equivalence to our predicate device the estimated bias between blood and plasma was determined. A bias to plasma of no greater than 10% was observed across all blood samples tested. This data supports the claim of equivalence between the two sample types and equivalence to our predicate device.

#### b) Precision / Reproducibility

The test is designed to have total imprecision < 10% CV for concetrations of hCG above 14 IU/L, or a standard deviation (SD) of 1.4 IU/L for concentrations of hCG < 14 IU/L in blood and plasma. Precision of the i-STAT Total ß-hCG test was evaluated in whole blood and plasma. The precision in blood and plasma was demonstrated at three external POC sites.

In whole blood, samples were targeted at four hCG concentrations: 5 IU/L, 25 IU/L, Mid level (~800 IU/L) and High level (~1500 IU/L). The highest observed upper (total) imprecision at 5 IU/L was 0.81 IU/L. The highest observed (total) imprecision was 7.3 %CV at all other levels.

In plasma, samples were targeted at four hCG concentrations: 5 IU/L, 25 IU/L, mid level (~1150 IU/L) and high level (~1875 IU/L). The observed (total) imprecision at 5 IU/L was 1.03 IU/L. The highest observed (total) imprecision was 5.6 %CV at all other levels.

Image /page/8/Picture/17 description: The image shows the logo for Abbott. On the left is a blue symbol that resembles a stylized letter 'a'. To the right of the symbol is the word "Abbott" in bold, black letters. Below the word "Abbott" is the phrase "A Promise for Life" in a smaller font size.

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Image /page/9/Picture/0 description: The image shows the logo for Abbott, a global healthcare company. The logo consists of a stylized letter 'a' in a bold, sans-serif font. The 'a' is enclosed within a rounded square shape, and the entire logo is colored in a light blue hue.

### c) Linearity / Test Measuring Interval

The linearity of the i-STAT Total B-hCG test was evaluated on the i-STAT System by creating a series of concentration levels in both whole blood and plasma through a process of mixing different proportions of low and high positive ß-hCG samples. The samples tested ranged in concentration from 5 IU/L to >2000 IU/L. In whole blood, the bias due to non-linearity was found to be 0.1 IU/L at the lowest hCG concentration. The percent non-linearity measured in whole blood did not exceed 4.1% across all levels between 10 and ~2000 IU/L. In plasma, the bias due to nonlinearity was found to be -0.1 IU/L at the lowest hCG concentration. The percent non-linearity measured in plasma did not exceed 2.3% across all levels between 10 and ~2000 IU/L.

### d) Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ)

The Limit of Blank (LoB) was determined using blank plasma and fresh whole blood that measured < 1.20 IU/L on the ARCHITECT system. One hundred and ninety five (195) replicate measurements in plasma and 144 replicate measurements in blood were used for this determination. Testing was completed over five days using two unique lots of i-STAT Total ß-hCG cartridges from two unique ß-hCG reagent sets.

The Limit of Detection (LoD) determination was based on 24 replicate measurements on each of six low level ß-hCG blood samples. This study included the use of 29 i-STAT 1 Analyzers and spanned five testing days and two unique i-STAT Total ß-hCG cartridge lots using two unique ß-hCG reagent sets.

The Limit of Quantitation (LoQ) determination was based on 92 replicate measurements of six low level ß-hCG blood samples. This study included the use of 13 i-STAT Analyzers and spanned six testing days using two unique i-STAT Total B-hCG cartridge lots from two unique ß-hCG reagent sets.

The LoQ was determined to be < 5.0 IU/L, the LoD was determined to be ≤ the LoQ and the LoB was determined to be < the LoD.

### e) High dose 'Hook Effect'

The i-STAT Total B-hCG test has a reportable range of 5.0 IU/L to 2000.0 IU/L. In an in-house study, no hook effect was observed up to ~450,000 IU/L in plasma and

Image /page/9/Picture/12 description: The image shows the Abbott logo. The logo consists of a stylized blue letter "A" on the left, followed by the word "Abbott" in bold, black letters. Below the word "Abbott" is the tagline "A Promise for Life" in a smaller, lighter font.

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Image /page/10/Picture/0 description: The image shows the logo for Abbott, a global healthcare company. The logo consists of a stylized letter 'a' in a light blue color. The 'a' is designed with rounded corners and a modern, minimalist aesthetic. The logo is simple, clean, and easily recognizable.

up to ~650,000 IU/L in whole blood. These results support the design goal of no significant hook effect up to 300,000 IU/L.

# f) Analytical Specificity

Three studies for analytical specificity were performed following CLSI guideline EP07-02. The first study used human plasma with ~ 50 IU/L and ~1500 IU/L hCG that was spiked with known interference substances. No significant interference, defined as recovery within ± 10% compared to reference without any interfering substance, was observed. The second study used human plasma with ~50 IU/L and ~1500 IU/L hCG that was spiked with the following interferents: Albumin, Bilirubin, Cholesterol, Hemoglobin, Triglyceride and Uric Acid. No significant interference, defined as recovery within ± 10% compared to reference without any interfering substance, was observed. The third study used human whole blood and plasma with ~5 IU/L hCG that was spiked with the same known interference substances as in previous studies. No significant interference, defined as recovery within +/- 4 IU/L compared to reference without interfering substance, was observed.

The cross-reactivity of the i-STAT Total ß-hCG test with glycoproteins of similar structure, namely Thyroid Stimulating Hormone (TSH), Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) was evaluated. The following levels were tested: 100 mIU/L TSH, 300 IU/L FSH and 450 IU/L LH. No significant interference, defined as recovery within ± 10% compared to reference without any interfering substance, was observed with the test.

Potential interference from human anti-mouse antibody (HAMA) and Rheumatoid factor (RF) was evaluated using 17 human plasma samples that had been prescreened as interferents to our test (each containing HAMA and/or RF). All sample interference was mitigated using the i-STAT Total ß-hCG test.

### g) Recovery

A dilution recovery study was performed using heparinized whole blood and plasma samples from six donors. For each donor, the original negative sample and ß-hCG spiked samples were prepared with WHO 5th IS (07/364) in either heparinized whole blood or heparinized plasma to approximately 2000 IU/L. The spiked samples were diluted using unspiked whole blood or plasma and tested in a minimum of ten cartridges. A series of nine levels were generated for each donor. For samples with hcg concentrations >5 IU/L, the individual recovery results for whole blood ranged from 91.1% to 118.5%, and for plasma samples from 81.8% to 103.3% when compared to WHO hCG 5th IS. For whole blood samples with hCG at a concentration of ~5 IU/L, the individual bias ranged from 0.3 to 1.1 IU/L, and for plasma samples from -0.2 to -1.2 IU/L when compared to WHO hCG 5th IS. End-

Image /page/10/Picture/10 description: The image contains the Abbott logo. On the left is a blue stylized letter 'A'. To the right of the 'A' is the word 'Abbott' in bold, black letters. Below 'Abbott' is the phrase 'A Promise for Life' in a smaller font.

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users may obtain individual result > 15% negative bias for plasma samples when hCG concentrations are >5 IU/L.

Image /page/11/Picture/4 description: The image shows the logo for Abbott. The logo consists of a stylized letter "a" in blue, followed by the word "Abbott" in black, bold font. Below the word "Abbott" is the tagline "A Promise for Life" in a smaller, black font.

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Percent recovery results were pooled across each hCG concentration.

| Level | Expected<br>Mean (IU/L) | Observed<br>Mean (IU/L) | % Recovery or<br>Absolute Bias |
|-------|-------------------------|-------------------------|--------------------------------|
| 1 | 1936.4 | 1974.6 | 102.0 % |
| 2 | 972.7 | 989.3 | 101.7 % |
| 3 | 644.8 | 677.4 | 105.1 % |
| 4 | 484.2 | 509.5 | 105.2 % |
| 5 | 242.2 | 261.4 | 107.9 % |
| 6 | 121.3 | 128.2 | 105.7 % |
| 7 | 60.6 | 62.9 | 103.8 % |
| 8 | 24.3 | 26.6 | 109.5 % |
| 9 | 5.1 | 5.8 | 0.7 IU/L |

### Summary Recovery Performance. Whole Blood

### Summary Recovery Performance, Plasma

| Level | Expected<br>Mean (IU/L) | Observed<br>Mean (IU/L) | % Recovery or<br>Absolute Bias |
|-------|-------------------------|-------------------------|--------------------------------|
| 1 | 1972.6 | 1811.5 | 91.8 % |
| 2 | 986.5 | 895.5 | 90.8 % |
| 3 | 657.5 | 622.1 | 94.6 % |
| 4 | 493.3 | 475.0 | 96.3 % |
| 5 | 246.9 | 234.1 | 94.8 % |
| 6 | 123.5 | 109.2 | 88.4 % |
| 7 | 61.8 | 54.5 | 88.2 % |
| 8 | 24.8 | 22.6 | 91.0 % |
| 9 | 5.3 | 4.5 | 0.8 IU/L |

# 9. i-STAT Total β-hCG Controls and Calibration Verification Performance Characteristics:

The i-STAT Total ß-hCG Control and Calibration Verification materials are manufactured by Cliniqa (k121237). The materials were evaluated and cleared for market use in k12137.

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### 10. Comparison Studies:

#### Method Comparison with Predicate Device a)

Method comparison data were collected following CLSI guideline EP9-A2. Blood samples were collected at the POC at four external sites in heparinized evacuated tubes, and analyzed in duplicate on the i-STAT System. The blood tubes were sent to the laboratory and the plasma portion was separated from the red cells. The plasma portion was tested in duplicate on the i-STAT System and the ARCHITECT system within 6 hours of collection. A total of 134 samples spanning the measuring interval of the i-STAT Total ß-hCG test were collected. The data was evaluated by weighted Deming regression analysis, using the first result of each duplicate measurement, and the results were as follows:

| Plasma samples: | $y = 1.02x - 0.22, r = 0.99, n = 134$ |
|----------------------|---------------------------------------|
| Whole blood samples: | $y = 0.95x + 2.39, r = 0.99, n = 134$ |

#### b) Sample Matrix Comparison

Sample matrix comparison was conducted based on the recommendations of CLSI guideline EP9-A2. Forty levels of hCG across and beyond the intended measurement interval of the i-STAT Total ß-hCG test were prepared using 40 donor samples and spiking each with a stock solution containing hCG antigen. The study took place over 12 testing days and the samples were run in random order across the measurement interval. Four sample types were investigated; lithium-heparin (Li-Hep) whole blood and plasma and sodium-heparin (Na-Hep) whole blood and plasma. Results of each sample type against the control (Li-Hep plasma) were analyzed. All Deming regression slopes comparing the sample type investigated with the control fell between 0.9 and 1.1.

#### 11. Reference Range:

Lithium heparin whole blood and plasma specimens from 123 apparently healthy. non-pregnant females ≥ 18 and < 40 years and from 125 apparently healthy, nonpregnant females > 40 years were collected and tested at four external sites. Subjects self-reported their menopausal status, which was defined as 12 months since last menses.

The 95th percentile and 95% confidence interval were calculated non-parametrically based on CLSI EP28-A3c.

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| Reference<br>Population<br>age (years) | N<br>Subjects | N<br>Whole<br>blood<br>results | N<br>Plasma<br>results | Median<br>(IU/L) | Range<br>(IU/L) | 95th Percentile<br>(IU/L), [95% CI] |
|----------------------------------------|---------------|--------------------------------|------------------------|------------------|-----------------|-------------------------------------|
| ≥ 18 and < 40 | 123 | 122 | 120 | 0 | 0 – 3.9 | 0.7 [0.3, 1.6] |
| ≥ 40 y | 125 | 125 | 124 | 0 | 0 – 9.6 | 4.5 [4.0 , 5.4] |
| ≥ 40 y, pre-<br>menopausal | 68 | 68 | 68 | 0 | 0 - 2.5 | -- |
| ≥ 40 y post-<br>menopausal | 57 | 57 | 56 | 1.5 | 0 – 9.6 | -- |

#### 12. Proposed Labeling:

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

#### 13. Conclusion:

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

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