The Access Total (BhCG (5th IS) assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of total BhCG levels in human serum and plasma using the Access Immunoassay Systems. The assay is intended for use as an aid in the early detection of pregnancy.

The Access Total BhCG (5th IS) calibrators are intended to calibrate the Access Total BhCG (5" IS) assay for the quantitative determination of total BhCG levels in human serum and plasma using the Access Immunoassay Systems.

Device Description

The Access Total βhCG (5" IS) assay (standardized to WHO 5" International Standard), Access Total BhCG (5th IS) calibrators, and the Access Immunoassay analyzers comprise the Access Immunoassay System for the quantitative determination of total βhCG in human serum and plasma.

AI/ML Overview

The provided text describes the performance of the Beckman Coulter Access Total βhCG (5th IS) Assay and Calibrators. The primary "acceptance criteria" for this device, as presented in the 510(k) summary, are derived from various analytical performance studies, which aim to demonstrate substantial equivalence to a predicate device.

Here's an analysis based on your requested information:

1. A table of acceptance criteria and the reported device performance

The document doesn't explicitly state "acceptance criteria" as a separate compiled list. Instead, performance characteristics are presented as results from various studies. I will infer the acceptance criteria from the reported results and the context of device validation for regulatory submission (e.g., meeting established thresholds for imprecision, linearity, etc.).

Acceptance Criteria (Inferred)	Reported Device Performance
Method Comparison (vs. Predicate):
Slope of Passing-Bablok regression: Approximately 1.00 (CI around 1.00)	Slope = 1.04 (95% CI: 1.02 to 1.06)
Intercept of Passing-Bablok regression: Approximately 0 mIU/mL	Intercept = 2.87 mIU/mL
Pearson correlation (r): Close to 1.00	r = 0.99
Imprecision (CV% or SD):
Total imprecision for concentrations > 3.9 mIU/mL: < 10% CV	Total imprecision: 2.6 to 6.6 %CV
Total imprecision for concentrations < 3.9 mIU/mL: < 0.39 SD	Total imprecision: < 0.39 SD (at concentrations < 3.9 mIU/mL)
High-dose Hook Effect:
No high-dose hook effect observed within expected range	No high-dose hook to 1,000,000 mIU/mL
Linearity:
Linear across the assay range	Linear across the range of the assay (0.6 to 1350 mIU/mL)
Dilution Recovery:
Average recovery: 100 ± 15%	Average recovery: 100 ± 15% (for 200-fold dilution of samples 1150-270,000 mIU/mL)
Limit of Blank (LoB):
LoB: ≤ 0.5 mIU/mL	LoB: ≤ 0.5 mIU/mL
Limit of Detection (LoD):
LoD: ≤ 0.5 mIU/mL (95% probability)	LoD: ≤ 0.5 mIU/mL
Limit of Quantitation (LoQ):
LoQ: ≤ 0.6 mIU/mL	LoQ: ≤ 0.6 mIU/mL
Analytical Specificity:
No significant interference from common interferents	No significant interference from total protein, bilirubin, hemoglobin, or triglycerides. No significant cross-reactivity with similar substances.
Isoform Recognition:
Recognizes specified hCG isoforms	Recognizes intact hCG, ß subunit, nicked intact hCG, and nicked ßhCG isoforms. No detectable response from free ɑ-subunit and ß-core fragment.
Expected Values (Non-pregnant females):
100% of samples ≤ 11.6 mIU/mL	All measured samples (100%) were ≤ 11.6 mIU/mL
Matrix Comparison (Serum vs. Serum (gel), Serum vs. Plasma):
Slope (Serum vs. Serum (gel)): Approx. 1.00 (CI around 1.00)	Slope = 0.99 (CI: 0.98 to 1.01)
Intercept (Serum vs. Serum (gel)): Approx. 0 mIU/mL	Intercept = -0.05 mIU/mL (CI: -0.15 to 0.10 mIU/mL)
Slope (Serum vs. Plasma): Approx. 1.00 (CI around 1.00)	Slope = 1.05 (CI: 1.02 to 1.07)
Intercept (Serum vs. Plasma): Approx. 0 mIU/mL	Intercept = -0.08 mIU/mL (CI: -0.28 to 0.05 mIU/mL)

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Test Set Sample Size:
- Method Comparison: 224 serum samples
- Imprecision: Not explicitly stated, but samples were run multiple times.
- High-dose Hook Effect: One serum sample tested at 1,000,000 mIU/mL.
- Linearity: Not explicitly stated how many samples, but tested across range.
- Dilution Recovery: Samples containing hCG from ~1150 mIU/mL to 270,000 mIU/mL (number of distinct samples not specified).
- Limit of Blank (LoB): n=156 (samples with no analyte).
- Analytical Specificity: Patient serum sample with ~2.9 mIU/mL hCG.
- Expected Values: 100% of samples (number not specified) from apparently healthy non-pregnant females.
- Matrix Comparison: 42 matched sets of serum (gel and no gel) and plasma (lithium-heparin) samples.
Data Provenance: Not specified (e.g., country of origin, retrospective/prospective). This is common for this type of 510(k) summary, as it generally focuses on analytical performance, not clinical trial data which typically provides more demographic/provenance detail.

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

This is an analytical device for quantitative measurement of a biomarker. The "ground truth" for such devices is typically established by:

Measurement against a highly standardized reference material (e.g., WHO International Standard).
Quantitative comparison to an established, legally marketed predicate device.
The inherent properties of the measured analyte (concentration, linearity, etc.).

There are no human experts involved in establishing ground truth for the analytical performance studies described in this 510(k) summary, as it's not and image-based or diagnostic interpretation device.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

None. Adjudication methods are typically employed in studies where human interpretation (e.g., of medical images) is involved and a consensus or tie-breaking mechanism is needed to establish ground truth or resolve discrepancies between readers. This device is an automated immunoassay system, not subject to human interpretative variability in the same way.

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

No. An MRMC study is not applicable to this type of immunoassay device. MRMC studies are used for evaluating diagnostic devices that involve human interpretation (like radiology or pathology) and are designed to determine how a new technology (e.g., AI) impacts human reader performance.

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

Yes, the studies presented are standalone algorithm-only performance evaluations for the immunoassay. The device (Access Total βhCG assay and Access Immunoassay Systems) performs the quantitative measurement automatically without human interpretative input in the analytical process itself. The "algorithm" here refers to the assay's chemical and detection methodology and the instrument's processing of signals.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" for the analytical performance studies is established by:

Comparison to a predicate device: The Siemens ADVIA Centaur Total hCG Assay (e.g., in the Method Comparison study). The predicate device itself represents a current standard for hCG measurement.
Reference materials/standards: The assay is standardized to WHO 5th International Reference Preparation, Chorionic Gonadotropin, NIBSC Coded 07/364. This is the ultimate ground truth for concentration measurements.
Known concentrations: For studies like linearity, dilution recovery, LoB, LoD, LoQ, samples with known or precisely formulated concentrations are used to verify the assay's ability to accurately measure these.
Biological state: For "Expected Values" studies, the ground truth is the physiological state of the subjects (e.g., apparently healthy non-pregnant females).

8. The sample size for the training set

The provided document describes analytical validation studies, not the development or training of a machine learning model. Therefore, there is no specific "training set" mentioned in the context of typical machine learning. The term "training set" is not applicable to the validation of this chemical immunoassay.

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

As there is no "training set" in the context of a machine learning algorithm, this question is not applicable. The assay's chemical and enzymatic reactions (its "design") are based on established biochemical principles and are not "trained" on data in the same way an AI model is.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for Beckman Coulter. The logo consists of a circular graphic on the left and the words "BECKMAN" and "COULTER" stacked on top of each other on the right. The circular graphic appears to have a stylized design within it, possibly representing a fluid or wave pattern.

510(k) Summary Prepared September 30, 2013

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

Submitter's Name and Address

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

Primary Contact: Geraldine Baglien (952) 368-7645 (952) 368-7610 (fax)

Alternate Contact: Jeffrey Koll (952) 368-1361 (952) 368-7610 (fax)

Device Name

Trade Name:	Access Total βhCG (5th IS) Assay and Access TotalβhCG (5th IS) Calibrators on the Access®Immunoassay Systems
Common Name:	Human chorionic gonadotropin
Classification Name:	Human chorionic gonadotropin (HCG) test system(21 CFR 862.1155)Secondary Calibrator (21CFR 862.1150)

Predicate Device

ADVIA Centaur Total hCG Assay (K925277) Manufactured by Siemens Healthcare Diagnostics, Inc.

OCT 0 1 2013

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Device Description

Intended Use

The Access Total (ShCG (5th IS) assay is a paramagnetic particle, chemiluminescent immunoassay for the in vitro quantitative determination of total βhCG levels in human serum and plasma using the Access Immunoassay Systems. This assay is intended for use as an aid in the early detection of pregnancy.

The Access Total βhCG (5th IS) Calibrators are intended to calibrate the Access Total BhCG (5" IS) assay for the quantitative determination of total BhCG levels in human serum and plasma using the Access Immunoassay Systems.

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Comparison of Technological Characteristics

Parameter	Access Total BhCG (50" IS)	Predicate ADVIA Centaur Total
	Assay and Access Total BhCG	hCG
	(5th IS) Calibrators
Intended use	The Access Total BhCG (5th IS)assay is a paramagnetic particle,chemiluminescent immunoassayfor the quantitative determinationof total BhCG levels in humanserum and plasma using theAccess Immunoassay Systems.This assay is intended for use asan aid in the early detection ofpregnancy.The Access Total BhCG (5th IS)Calibrators are intended tocalibrate the Access Total BhCG(5" IS) assay for the quantitativedetermination of total BhCG levelsin human serum and plasma usingthe Access ImmunoassaySystems	For in vitro diagnostic use in thequantitative determination ofhuman chorionic gonadotropin(hCG) in serum using the ADVIACentaur and ADVIA Centaur XPsystems. The results obtained fromhCG specimens are used as an aidin the assessment of pregnancystatus. The assay detects theintact hCG molecule and free beta-subunit of the hCG molecule
Analyte Measured	Total BhCG (intact hCG and freebeta-subunit)	Intact hCG and free beta-subunithCG
Standardization	WHO 50 International ReferencePreparation, ChorionicGonadotropin, NIBSC Coded07/364	WHO 4th International ReferencePreparation, ChorionicGonadotropin, NIBSC Coded75/589
Technology	Sandwich immunoassay	Sandwich immunoassay
Format	Chemiluminescent	Chemiluminescent
Method	Automated	Automated
Calibration	Utilizes a stored calibration curve	Utilizes a stored calibration curve
Calibrator Levels	6 levels(0 mlU/mL, and approximately 6,35, 195, 620 and 1350 mlU/mL)	2 levels(Low at approximately 7 mIU/mLand High at approximately 300mlU/mL)
Calibrator Matrix	Bovine serum albumin	Equine serum
Calibration CurveStability	28 days	28 days
Sample Type	Serum or plasma	Serum
Measuring Range	0.6 - 1350 mIU/mL (IU/L)	2.0 - 1000 mIU/mL (IU/L)

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Summary of Studies

Method Comparison: A comparison of 224 serum samples with hCG concentrations ranging from approximately 3.2 to 1095.9 mIU/mL were run on both the Access Total BhCG (5th IS) immunoassay and the predicate Siemens ADVIA Centaur Total hCG immunoassay. The results were compared using Passing-Bablok regression and Pearson correlation with the predicate on the x-axis. The observed linear fit had a slope = 1.04 with 95% confidence interval of 1.02 to 1.06, an intercept = 2.87 mIU/mL and a r = 0.99.

Imprecision: Serum and plasma samples within run imprecision ranged from 1.8 to 4.8 %CV, between run imprecision ranged from 0.9 to 6.0 %CV, and total imprecision ranged from 2.6 to 6.6 %CV at levels between 3.9 and 1350 mlU/mL. The assay exhibits total imprecision of less than 10% CV for concentrations greater than 3.9 mIU/mL and < 0.39 SD at concentrations < 3.9 mlU/mL.

High-dose Hook Effect: The Access Total BhCG (5" IS) assay demonstrated no highdose hook to 1,000,000 mIU/mL in a serum sample.

Linearity: The Access Total BhCG (5" IS) assay has demonstrated to be linear across the range of the assay (0.6 to 1350 mlU/mL) in serum samples.

Dilution Recovery: The Access Total βhCG (5th IS) assay has been demonstrated to dilute recover across the range of the assay (0.6 to 1350 mIU/mL) in serum and plasma samples. Samples containing hCG concentrations from approximately 1150 mIU/mL to 270,000 mlU/mL can be diluted 200-fold and average recovery 100 ± 15%.

Limit of Blank (LoB): The highest measurement result observed with no analyte present in a serum sample is ≤ 0.5 mIU/mL (n=156).

Limit of Detection (LoD): The lowest concentration of analyte in a serum sample that can be detected with a stated probability (95%) is ≤ 0.5 mIU/mL.

Limit of Quantitation (LoQ): The lowest concentration of analyte in serum and plasma samples that can be quantitatively determined is ≤ 0.6 mIU/mL.

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Analytical Specificity: There is no significant interference from total protein, bilirubin, hemoglobin, or triglycerides in serum samples. Additionally, substances similar in structure to hCG when added to a patient serum sample with an approximate hCG concentration of 2.9 mlU/mL showed no significant cross-reactivity.

Isoform Recognition: In serum samples, the Access Total BhCG 5th IS assay recognizes intact hCG, the ß subunit of hCG, nicked intact hCG and nicked ßhCG isoforms. The free a-Dsubunit and B-core fragment vield no detectable response.

Expected Values: Total BhCG concentrations were measured in human serum samples collected from apparently healthy non-pregnant females, which included premenopausal and post-menopausal women, using the Access Total ßhCG (5" IS) assay. Concentrations of total ßhCG measured in 100% of samples were determined to be ≤ 11.6 mIU/mL (IU/L).

Matrix Comparison: A comparison of forty-two (42) matched sets of serum (gel and no gel) and plasma (lithium-heparin) samples with hCG concentrations ranging from approximately 0.5 to 1350 mlU/mL were compared using Passing-Bablok regression with serum (no gel) on the x-axis. The observed linear fit for serum vs. serum (gel) had an estimated slope = 0.99 with a confidence interval (CI) of 0.98 to 1.01, and an estimated intercept = -0.05 mlU/mL with a Cl of -0.15 to 0.10 mlU/mL. The observed linear fit for serum vs. plasma had an estimated slope = 1.05 with a Cl of 1.02 to 1.07, and an estimated intercept = -0.08 mlU/mL with a Cl of -0.28 to 0.05 mlU/mL.

Conclusion:

The Access Total BhCG (5" IS) Assay and Access Total BhCG (5th IS) Calibrators, for use on the Access Immunoassay Systems, are substantially equivalent to the predicate device, Siemens ADVIA Total hCG assay (K925277) for the measurement of hCG and are safe and effective for their intended use.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WOods-Gh(19 Silver Spring, MI) 20993-1602

October 1. 2013

Beckman Coulter, Inc. c/o Geraldine L. Baglien 1000 Lake Hazeltine Drive CHASKA MN 55318-1084

Re: K130020 Trade/Device Name: Access Total BhCG (5th IS) Assay Access Total BhCG (5th IS) Calibrators Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: II Product Code: DHA, JIX Dated: September 17, 2013 Received: September 18, 2013

Dear Ms. Baglien:

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 conninered prior to May 2011 and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). Tou may, therefore, market the device, subject to the general controls provisions of the Act. The I ou may. therefore. manner of the Act include requirements for annual registration, listing of general controls provisions or actice. labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability additiciation. Thease note: ODTC: Set 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). If your device is classince (see above) meeting 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 that I DA has made a coloring administered by other Federal agencies. You must of any Federal Statures and regulations and limited to: registration and listing (21 comply with an the Act 3 requirements, morading, or medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements medical device-related adverse events) (2) regulation (21 CFR Part 820); and if applicable. the as set form in the quality systems (20) regaration (Sections 531-542 of the Act): 21 CFR 1000-1050.

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Page 2-Ms. Baglien

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 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" (21CFR 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 Fou may of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Carol C. Benson -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): K130020

Device Name: Access Total BhCG (5th IS) Assay and Access Total BhCG (5th IS) Calibrators on the Access® Immunoassay Systems.

Indications for Use:

Prescription Use X (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Denise Johnson-lyles -5 2013.10.01 09:47:48 -04'00'

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

510(k)_k130020

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.