For quantitative measurement of human chorionic gonadotropin (hCG) and its ß-subunit in human serum and plasma (EDTA or heparin) to aid in the early detection of pregnancy.

For use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of human chorionic gonadotropin (hCG) and its ß-subunit in human serum and plasma (EDTA or heparin).

For in vitro use in verifying the calibration range of the VITROS Immunodiagnostic System when used for the measurement of human chorionic gonadotropin (hCG) and its ß-subunit.

Device Description

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system.

The assay is comprised of three main elements:

The VITROS Immunodiagnostic Products range of immunoassay products in this case the VITROS Immunodiagnostic Products Total B-hCG II Reagent Pack, the VITROS Immunodiagnostic Products Total B-hCG II Calibrators, and the VITROS Immunodiagnostic Products Total B-hCG II Range Verifiers (which are combined by the VITROS Immunodiagnostic system to perform the VITROS Total B-hCG II assay).
The VITROS Immunodiagnostic System - instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
Common reagents - used by the VITROS Immunodiagnostic System in each assay include the VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 Reagent Pack and VITROS Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).

Note: High Sample Diluent B was cleared as part of the VITROS Immunodiagnostic Products Total B-hCG Reagent Pack and VITROS Immunodiagnostic Products Total β-hCG Calibrators 510(k) premarket notification (K970894).

The VITROS Immunodiagnostic System and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products.

AI/ML Overview

Here's an analysis of the provided 510(k) summary regarding the acceptance criteria and study details for the VITROS Immunodiagnostic Products Total β-hCG II assay.

Please note: This document is a 510(k) summary for an in-vitro diagnostic device, not an AI/ML-based medical device. Therefore, many of the requested categories (e.g., sample size for test set/training set, number of experts for ground truth, adjudication method, MRMC study, human reader improvement) are not applicable or available in this type of submission. This summary focuses on demonstrating substantial equivalence to a predicate device, primarily through performance characteristics of the assay itself.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the new device are implicitly established by demonstrating substantial equivalence to the predicate device. This is primarily done by comparing performance characteristics such as analytical sensitivity, specificity, precision, and measuring range, and showing that the new device performs comparably or better.

Here's a table summarizing the reported device performance compared to the predicate, which serves as the de-facto acceptance criteria. The new device must meet or exceed the performance of the predicate to demonstrate substantial equivalence.

Characteristic	Predicate Device Performance (Acceptance Criteria)	New Device Performance (Reported)
Analytical Sensitivity	≤ 1.2 mIU/mL	0.70 mIU/mL
Specificity	≤ 10% for FSH, LH, and TSH	≤ 10% for FSH, LH, and TSH
Within-Run Precision	1.2-4.7% CV	1.1-2.5% CV
Total/Within-Lab Precision	1.6-4.9% CV	2.9-4.2% (Within-lab) CV
Measuring Range	Up to 15,000 mIU/mL	Up to 15,000 mIU/mL

Note: The "Expected Values" table is also presented for comparison, but these are typically reference ranges derived from clinical populations rather than strict acceptance criteria for the device's technical performance.

Study Details

Given this is a 510(k) for an in-vitro diagnostic assay (laboratory test), the study design differs significantly from that of an AI/ML device.

Sample size used for the test set and the data provenance:
- The document does not explicitly state a "test set" sample size in the context of a diagnostic test for comparing against ground truth. Instead, performance characteristics (precision, sensitivity, specificity, measuring range) are evaluated using various types of samples.
- Specificity and Analytical Sensitivity: The document states 0.70 mIU/mL analytical sensitivity and ≤ 10% cross-reactivity for FSH, LH, and TSH without providing specific sample counts for these tests.
- Precision: Precision studies involved measuring samples multiple times to calculate Coefficients of Variation (CV). The specific number of samples for these studies is not detailed in the summary, but typical studies involve multiple replicates over several days with different operators and instrument runs.
- Expected Values: The table for "Expected Values" in Table 1 shows sample sizes (n) for different gestational age groups: 1-10 weeks (n=112 for new device, n=50 for predicate), 11-15 weeks (n=43 for new device, n=50 for predicate), 16-20 weeks (n=50 for new device, n=50 for predicate), and 23-40 weeks (n=45 for new device, n=50 for predicate). This data provenance is generally from clinical populations.
- Data Provenance: Not explicitly stated as retrospective or prospective, nor country of origin for all performance data, though the manufacturer site is in the United Kingdom. The "Expected Values" imply clinical samples.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable / Not explicitly stated. For an immunoassay, the "ground truth" for analytical performance tests (sensitivity, specificity, precision) is established through reference methods, certified reference materials, and standardized laboratory practices, not typically by expert consensus of human readers. For clinical reference ranges ("Expected Values"), the ground truth is derived from the measured hGC levels in a healthy population or population with known pregnancy status, often confirmed by clinical means (e.g., last menstrual period, ultrasound), but not requiring human expert adjudication of visual data.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. Adjudication methods like 2+1 are used for human interpretation of images or complex data where consensus is needed to establish ground truth. For an automated immunoassay, the result is quantitative or qualitative based on the assay's chemical reaction and signal detection.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. An immunoassay is an automated diagnostic test; it does not involve human "readers" interpreting results in the way an AI medical device for image analysis would. Therefore, no MRMC study or assessment of human reader improvement with AI assistance was performed or is relevant.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, in essence. Immunoassays are inherently "standalone" in that once the sample is loaded and the test is run, the instrument produces the result without further human interpretation beyond reporting the quantitative value. The performance metrics discussed (sensitivity, specificity, precision, measuring range) are all measures of the device's standalone analytical performance.
The type of ground truth used (expert concensus, pathology, outcomes data, etc):
- The "ground truth" for demonstrating the performance of this in-vitro diagnostic device would typically involve:
  - Reference standards/materials: For analytical sensitivity and linearity, using known concentrations of hCG.
  - Clinical samples: For establishing expected values and potentially for cross-reactivity studies, samples from healthy individuals or individuals with confirmed conditions (e.g., pregnant patients, patients with elevated FSH/LH/TSH) might be used.
  - Comparative methods: Often, performance is validated by comparing results to a gold standard or well-established reference method.
- The document does not explicitly detail the exact nature of the "ground truth" for all studies, but it is inferable from the types of performance claims made.
The sample size for the training set:
- Not applicable. This device is an immunoassay, not an AI/ML algorithm that requires a "training set" in the computational sense. The assay's chemistry and detection principles are pre-determined during development, not "trained" on data.
How the ground truth for the training set was established:
- Not applicable. As there is no training set for an immunoassay, there is no ground truth established for it in this context.

Summary

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510(k) Summary I

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

K063720 The assigned 510(k) number is: _

Submitter Name, Address and Contact 1

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 (585) 453-4131

Contact Person: Sarah CV Parsons, RAC

Preparation Date 2

Date 510(k) prepared: December 14, 2006

3 Device Name

VITROS Immunodiagnostic Products Total β-hCG II Reagent Pack VITROS Immunodiagnostic Products Total β-hCG II Calibrators VITROS Immunodiagnostic Products Total ß-hCG II Range Verifiers

Common Name: Total ß-hCG II Assay

Classification Name(s): Human chorionic gonadotropin (HCG) test system (21 CFR 862.1155) Calibrators (21 CFR 862.1150) Ouality Control material (assayed and unassayed) (21 CFR 862.1660)

Classifications: The Clinical Chemistry and Toxicology Panel of the FDA has placed the Human chorionic gonadotropin (HCG) test system as a Class II Medical Device. The Microbiology Device Panel has classified Calibrators as Class II Medical Devices (21 CFR 862.1150). The Microbiology Device Panel has classified Controls as Class I Medical Devices (21 CFR 862.1660)

Product Code: DHA, JIT, JJX

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Manufacturing Establishment 9680658 Registration Number:

Ortho Clinical Diagnostics, Inc. Manufacturer Site: Forest Farm Estate Cardiff United Kingdom CF14 7YT

Predicate Device 4

5 Device Description

The assay is comprised of three main elements:

The VITROS Immunodiagnostic Products range of immunoassay products in this case the VITROS Immunodiagnostic Products Total B-hCG II Reagent Pack, the VITROS Immunodiagnostic Products Total B-hCG II Calibrators, and the VITROS Immunodiagnostic Products Total B-hCG II Range Verifiers (which are combined by the VITROS Immunodiagnostic system to perform the VITROS Total B-hCG II assay).
The VITROS Immunodiagnostic System - instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
Common reagents - used by the VITROS Immunodiagnostic System in each assay include the VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 Reagent Pack and VITROS Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).

Note: High Sample Diluent B was cleared as part of the VITROS Immunodiagnostic Products Total B-hCG Reagent Pack and VITROS

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Immunodiagnostic Products Total β-hCG Calibrators 510(k) premarket notification (K970894).

The VITROS Immunodiagnostic System and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products.

Device Intended Use 6

VITROS Immunodiagnostic Products Total B-hCG II Reagent Pack For quantitative measurement of human chorionic gonadotropin (hCG) and its ßsubunit in human serum and plasma (EDTA or heparin) to aid in the early detection of pregnancy.

VITROS Immunodiagnostic Products Total ß-hCG II Calibrators For use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of human chorionic gonadotropin (hCG) and its ßsubunit in human serum and plasma (EDTA or heparin).

VITROS Immunodiagnostic Products Total ß-hCG II Range Verifiers For in vitro use in verifying the calibration range of the VITROS Immunodiagnostic System when used for the measurement of human chorionic gonadotropin (hCG) and its ß-subunit.

7 Comparison to Predicate Device

Ortho-Clinical Diagnostics, Inc. believes that the VITROS Immunodiagnostic Products Total B-hCG II assay and VITROS Immunodiagnostic Products Total BhCG II Range Verifiers are substantially equivalent to the Abbott Laboratories, ARCHITECT® SYSTEM Total B-HCG assay (K983424) assay and VITROS Immunodiagnostic Products Total B-hCG Range Verifiers (K973517). Tables 1 through 4 compare the VITROS Immunodiagnostic Products Total 3hCG II assay and Range Verifiers to the Abbott Laboratories, ARCHITECT® SYSTEM Total B-HCG II assay and VITROS Immunodiagnostic Products Total B-hCG Range Verifiers.

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Table 1 Comparison of the VITROS Immunodiagnostic Products Total βhCG II assay to the Abbott Laboratories, ARCHITECT® SYSTEM Total β-HCG assay: Similarities

Similarities
DeviceCharacteristic	New device	Predicate device
IntendedUse	For the quantitative measurement of humanchorionic gonadotropin (hCG) and its β-subunit inhuman serum and plasma (EDTA and heparin)	... for the quantitative and qualitative determinationof beta-human chorionic gonadotropin (β-hCG) inhuman serum and plasma ...
Basicprinciple	chemiluminescent immunometric assay	Chemiluminescent Microparticle Immunoassay
Antibody	conjugated monoclonal mouse anti-β-hCG	Conjugated monoclonal mouse anti-β-hCG
Sampletype	Serum and Plasma (EDTA and heparin)	Serum and Plasma (EDTA and heparin)
ExpectedValues	LMP n Min Max 2.5 97.5 1-10 112 44.71 256,740 63.7 150,854 11-15 43 11,556 265,380 11,795 151,996 16-20 50 7,480.8 111,954 9,383.8 61,410 23-40 45 1,531.1 101,566 1,737.2 98,576		LMP n Min Max 2.5 97.5 1-10 50 <1.20 >225,000.00 201.6 >225,000.00 11-1 50 16,995.65 >225,000.00 22,536.49 >225,000.00 16-20 50 8,860.23 >225,000.00 8,006.62 50,238.60 23-40 50 1,583.40 65,911.30 1,599.80 49,412.65
MeasuringRange	Up to 15,000 mIU/mL	Up to 15,000 mIU/mL
Precision	Within-Run (CV 1.1-2.5%), Within-lab (2.9-4.2%)	Within-Run (CV 1.2-4.7%), Total (CV 1.6-4.9%)
AnalyticalSensitivity	0.70 mIU/mL	≤ 1.2 mIU/mL
Specificity	≤ 10% for FSH, LH and TSH	≤ 10% for FSH, LH and TSH

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Comparison of the VITROS Immunodiagnostic Products Total ß-Table 2 hCG II assay to the Abbott Laboratories, ARCHITECT® SYSTEM Total ß-HCG assay: Differences

Differences
DeviceCharacteristic	New device	Predicate device
Intended Use	Indication not in statement.	... for the early detection of pregnancy
Sample volume	40 $ \mu $ L	75 $ \mu $ L
Antibodies	Biotin conjugated mousemonoclonal anti- $\beta$ -hCG	Mouse monoclonal anti- $\beta$ -hCG coatedmicroparticles.
Luminescent label	Horse radish peroxidase	acridinium
Instrumentation	VITROS ImmunodiagnosticSystem	ARCHITECT SYSTEM
Calibrator levels	Three levels	Six levels

Comparison of the VITROS Immunodiagnostic Products Total β-Table 3 hCG II Range Verifiers to the VITROS Immunodiagnostic Products Total ß-hCG Range Verifiers: Similarities

Similarities
DeviceCharacteristic	New device	Predicate device
Intended Use	For in vitro use in verifying thecalibration range of the VITROSImmunodiagnostic System whenused for the measurement ofhuman chorionic gonadotropin(hCG) and its ß-subunit	For in vitro use in verifying thecalibration range of the VITROSImmunodiagnostic System whenused for the measurement of humanchorionic gonadotropin (hCG) andits ß-subunit
Levels	Low and High	Low and High
Format	Freeze-dried	Freeze-dried

Comparison of the VITROS Immunodiagnostic Products Total β-Table 4 hCG II Range Verifiers to the VITROS Immunodiagnostic Products Total β-hCG Range Verifiers: Differences

Differences
DeviceCharacteristic	New device	Predicate device
Matrix	Human plasma	Bovine serum
Antigen	Bacterial Recombinant hCG	Purified from human urine hCG

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8 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS Total B-hCG II Reagent Pack, VITROS Total ß-hCG II Calibrator and VITROS Total ß-hCG II Range Verifiers are safe and effective for the stated intended uses and is substantially equivalent to the cleared predicate devices.

The VITROS Immunodiagnostic Products Total β-hCG II Reagent Pack and the VITROS Immunodiagnostic Products Total β-hCG II Calibrator were compared to the Abbott Laboratories, ARCHITECT® SYSTEM Total β-HCG assay. The VITROS Immunodiagnostic Products Total ß-hCG II Range Verifiers were compared to the VITROS Immunodiagnostic Products Total ß-hCG Range Verifiers.

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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus, a symbol often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES . USA" are arranged in a circular pattern around the caduceus. The logo is simple and monochromatic.

2098 Gaither Road

Rockville MD 20850

Food and Drug Administration

APR - 9 2007

Ms. Sarah CV Parsons, RAC Ortho-Clinical Diagnostics, Inc. Regulatory Affairs, MC00881 100 Indigo Creek Drive Rochester, NY 14626-5101

Re: K063720

Trade/Device Name: Vitros Immunodiagnostic Products Total B-HCG II reagent PA Vitros Immunodiagnostic Products Total B-HCG II Calibrators Vitros Immunodiagnostic Products Total B-HCG II Range Verifiers Regulation Number: 21 CFR § 862.1155 Regulation Name: Human Chorionic Gonadotropin (HCG) test system Regulatory Class: Class II Product Code: DHA, JIT, JJX Dated: March 26, 2007 Received: March 27, 2007

Dear Ms. Parsons:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Yean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use 1

Page 1 of 1

K063720

510(k) Number (if known):

Device Name:

VITROS Immunodiagnostic Products Total β-hCG II Reagent Pack VITROS Immunodiagnostic Products Total B-hCG II Calibrators VITROS Immunodiagnostic Products Total ß-hCG II Range Verifiers

Indications for

Use:

For quantitative measurement of human chorionic gonadotropin (hCG) and its ß-subunit in human serum and plasma (EDTA or heparin) to aid in the early detection of pregnancy.

For use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of human chorionic gonadotropin (hCG) and its ß-subunit in human serum and plasma (EDTA or heparin).

For in vitro use in verifying the calibration range of the VITROS Immunodiagnostic System when used for the measurement of human chorionic gonadotropin (hCG) and its ß-subunit.

Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

b63720

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.