The ACCESS® Total βhCG assay is a paramagnetic-particle, chemiluminescent immunoassay for the quantitative determination of total βhCG in human serum, using the the ACCESS® Immunoassay System.

Device Description

The Access® Total BhCG reagents and the Access® Immunoassay Analyzer comprise the Access® Immunoassay System for the quantitative determination of total βhCG levels in human serum.

AI/ML Overview

The document describes the acceptance criteria and supporting studies for the Access® Total βhCG assay.

Here's a breakdown of the requested information:

1. Table of acceptance criteria and the reported device performance:

Acceptance Criteria Category	Specific Metric (Criteria)	Reported Device Performance
Precision	Within-run precision: Not explicitly stated as a criterion, but demonstrated.	Ranges from 1.34% CV
	Total imprecision: Not explicitly stated as a criterion, but demonstrated.	Ranges from 2.41% CV to 3.38% CV
Accuracy	Dilution recovery: Mean recoveries for two human serum samples.	97% and 98% (for dilutions from 1:1.2 to 1:32)
Correlation	Comparison with predicate device (ACS:180 Total hCG +B assay): Slope and correlation coefficient (r) for 119 human serum samples.	Slope = 0.914, r = 0.98
Analytical Sensitivity	Lowest detectable level of βhCG distinguishable from zero.	0.5 mIU/ml
Analytical Specificity	Cross-reactivity with hLH, hFSH, or hTSH.	No significant cross-reactivity observed.
	Molar percent specificity of free βhCG subunit (WHO 75/551).	Approximately 200%
Hook Effect	Absence of hook effect at high concentrations.	No discernible hook effect at 1,000,000 mlU/ml. (Predicate assay: patient samples as high as 400,000 mlU/ml will assay > 1000 mlU/ml).
Assay Range	Measurement range.	0.5 mIU/ml - 1000 mIU/ml

2. Sample size used for the test set and the data provenance:

Correlation Study (comparison with predicate): 119 human serum samples.
Accuracy (Dilution Recovery): 2 human serum samples were diluted.
Precision: Not explicitly stated how many samples were used, but multiple runs/measurements would be implied by CV calculation.
Analytical Sensitivity: Data supports the lowest detectable level using Access® Total βhCG Calibrator S0.
Analytical Specificity: Not specified.
Data Provenance: The data used for these studies are described as "human serum samples." The document does not specify the country of origin of the data, nor does it explicitly state whether the study was retrospective or prospective. Given the nature of these types of lab validation studies, they are typically prospective evaluations of samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This device is an in-vitro diagnostic (IVD) assay used for the quantitative determination of βhCG. The "ground truth" for this type of device is established by the known concentration of βhCG in control materials or by comparison with a well-established and standardized reference method. The document does not mention human expert adjudication for establishing ground truth in the context of image interpretation or subjective assessments. Instead, it refers to:

Standardization: "Both assays are standardized to the WHO 3rd IS 75/537 standard." This international standard serves as the "ground truth" for hCG concentration.
Predicate Device Comparison: The ACS:180 Total hCG +B assay acts as a comparative reference, implying its results are considered a form of "ground truth" for comparison purposes.

Therefore, no human experts (e.g., radiologists) were used in the way one might for diagnostic imaging studies, as the ground truth is based on biochemical standards and established comparative assays.

4. Adjudication method for the test set:

Not applicable in the context of this IVD device. "Adjudication" usually refers to resolving discrepancies between multiple human readers or a human reader and an AI. For this quantitative immunoassay, the "ground truth" is determined by reference standards and established analytical methods, not human opinion or consensus.

5. 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. This is an in-vitro diagnostic assay, not an AI-assisted diagnostic imaging or human-in-the-loop system. Therefore, MRMC studies and "improvement with AI vs without AI assistance" are not relevant to this device.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

Yes, the studies describe the performance of the Access® Total βhCG assay as a standalone system (algorithm/reagent-only) when run on the Access® Immunoassay Analyzer. The results reported for precision, accuracy, analytical sensitivity, and specificity represent the performance of the device without human interpretation or intervention beyond the standard operation of the instrument.

7. The type of ground truth used:

The ground truth for this device's performance studies relies on:

Reference Standards: The WHO 3rd IS 75/537 standard for hCG concentration.
Known Concentrations: In spiked samples or controls for dilution recovery.
Comparative Reference Method: The ACS:180 Total hCG +B assay is used as a comparative "ground truth" for correlation studies.
Analytical Definitions: For sensitivity (lowest detectable level) and specificity (cross-reactivity with other hormones).

8. The sample size for the training set:

The document does not describe a "training set" in the context of machine learning. This is an immunoassay, not a machine learning algorithm that requires a separate training set. The assay's performance characteristics (e.g., calibration curves, sensitivity parameters) are established through a validation process, but this is distinct from training a machine learning model.

9. How the ground truth for the training set was established:

Not applicable, as there is no "training set" in the machine learning sense for this immunoassay. The standardization of the assay's calibration curve and parameters would be established by running known concentrations of calibrators (e.g., Access® Total βhCG Calibrator S0).

Summary

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APPENDIX 4

Summary of Safety and Effectiveness Information

January 19, 1997

1.	General InformationDevice Generic Name:	Enzyme Immunoassay, hCG
	Device Trade Name:	Access® Total βhCG assay
	Applicant's Name and Address:	Beckman Instruments, Inc.1000 Lake Hazeltine DriveChaska, MN 55318	Contact: Robert McCormack, Ph.D.612-368-1384

Predicate Device 2.

ACS:180 Total hCG B+

3. Device Description

The Access® Total BhCG reagents and the Access® Immunoassay Analyzer comprise the Access® Immunoassay System for the quantitative determination of total βhCG levels in human serum.

4. Indications for Use

The Access® Total ßhCG assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of total ßhCG levels in human serum using the AccEss® Immunoassay System.

Comparison of Technological Characteristics 5.

The Access® Total BhCG assay and the ACS:180 Total hCG +B assay are for the measurement of total BhCG in human serum. Both tests are two-site immunoassays and utilize monoclonal antibodies for capture and polycloncal antibodies as the second antibody. The Access® Total βhCG assay uses a dioxetane based chemiluminescent substrate while the ACS:180 Total hCG +B Kit uses an acridinium ester as the chemiluminescent substrate. Both assays are standardized to the WHO 3rd IS 75/537 standard and have available on-line dilution protocols. The AccEss® Total βhCG assay range is 0.5 mlU/ml - 1000 mlU/ml while the ACS:180 Total hCG +B assay range is 2 mlU/ml - 1000 mlU/ml. The Access® Total BhCG assay utilizes multi-level calibrators to establish a calibration curve and the ACS:180 Total hCG +B assay utilizes a set of two calibrators to reestablish calibration curves which have been set by the manufacturer and stored on the ACC:180. The Access® Total BhCG assay has no discernible hook effect at 1,000,000 mlUml. In the ACS:180 Total hCG +B assay patient samples as high as 400,000 mlU/ml will assay greater than 1000 mlU/ml.

Summary of Studies ર.

Precision studies: Within run precision ranges from 1.34% CV. Total imprecision ranges from 2.41% CV to 3.38% CV.

Accuracy: Dilution recovery studies performed by diluting 2 human serum samples from 1:1.2 to 1:32 with Access® Total BhCG Calibrator S0 results in mean recoveries of 97% and 98%.

Correlation: A comparison of hCG values from 119 human serum samples run in both the Access® Total BhCG assay and the ACS:180 Total hCG +B assay gives the following statistical data: slope = 0.914 and r= 0.98.

Analytical Sensitivity: The data supports the lowest detectable level of ßhCG distinguishable from zero (Access® Total BhCG Calibrator S0) is equal to 0.5 mIU/ml.

Analytical Specificity: No significant cross reactivity is observed with hLH; hFSH, or hTSH. The molar percent specificity of free ßhCG subunit (WHO 75/551) is approximately 200%.

7. Conclusion

The Access® Total BhCG reagents when used with the Access® Immunoassay Analyzer are substantially equivalent to another test in commercial distribution for the measurement of total ßhCG in human serum.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 18 1998

Sandy Frank Schwartz, Ph.D. . Senior Clinical and Regulatory Specialist Beckman Instruments, Inc. 1000 Lake Hazeltine Drive Chaska, Minnesota 55318-1084

Re : K980173 ACCESS® Total BhCG Assay Regulatory Class: II Product Code: JHI January 19, 1998 Dated: Received: January 20, 1998

Dear Dr. Schwartz:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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, Druq, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ಗಿ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements; as set forth in the Quality System Regulation (QS) for Medical Devices: General requlation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Reqister. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Gutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE STATEMENT

510(k) Number (if known):

Device Name: ACCESS® Total βhCG reagents on the ACCESS® Immunoassay Analyzer

Indications For Use:

The ACCESS® Total βhCG assay is a paramagnetic-particle, chemiluminescent immunoassay for the quantitative determination of total βhCG in human serum, using the the ACCESS® Immunoassay System.

SUMMARY AND EXPLANATION

Human chorionic gonadotropin (hCG) is a glycoprotein hormone, produced by the placenta, with structural similarity to the pituitary hormones FSH, TSH, and LH. The alpha subunit (MW 15,000-20,000 daltons) is common to all of these hormones but the beta subunits differ, and confer immunological and biological specificity. Beta hCG (MW 25,000-30,000 daltons) shares several peptide sequences with beta LH, but has a unique carboxyl terminal region (1-3).

Shortly after implantation of a fertilized ovum into the uterine wall, the trophoblast begins to produce hCG. The hormone maintains steroid secretions of the corpus luteum until the placenta can do so (4). During a normal pregnancy, serum hCG is approximately 50 mlU/ml (IU/I) in the week after conception, and doubles every 1.5-3 days for the first six weeks (5). Levels continue to rise until the end of the first trimester, then gradually fall to a lower level for the remainder of the pregnancy. After delivery, hCG returns to < 5 mlU/ml (IU/I) and is usually undetectable several days postpartum.

The hormone is an excellent marker for pregnancy. Healthy, non-pregnant individuals have low i< 5 mlU/ml (IU/l)] to undetectable hCG in serum. During pregnancy, hCG concentrations increase as noted above and then show a gradual decrease after the first trimester. Unusually low or rapidly declining levels may indicate an abnormal condition such as an ectopic pregnancy or impending spontaneous abortion (6).

Originally bioassay systems measured hCG by measuring gonadal tissue response in various animals. These methods exhibited insufficient sensitivity, were difficult to perform, and required large volumes of sample. Tests to measure urine hCG traditionally employed latex agquatination or agglutination inhibition methods. With the development of radioimmunoassay techniques for the measurement of hCG by Vaitukaitis et al. In 1972, more sensitive and rapid assays for hCG became available (7), Subsequent development of two-site immuno-radiometric assays (IRMA) provided assays with increased sensitivity, specificity, and precision (8).

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	Concurrence of CDRH, Office of Device Evaluation (ODE)
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Prescription Use

(Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

(Division Sign-Off)

Division of Clinical Laboratory Devices

510(k) Number	K980973
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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.