The Access TSH (3rd IS) assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of human thyroid-stimulating hormone (thyrotropin, TSH, hTSH) levels in human serum and plasma using the Access Immunoassay Systems. This assay is capable of providing 3rd generation TSH results.

The Access TSH (3rd IS) Calibrators are intended to calibrate the Access TSH (3rd IS) assay for the quantitative determination of human thyroid-stimulating hormone (thyrotropin, TSH, hTSH) levels in human serum and plasma using the Access Immunoassay Systems.

Device Description

The Access TSH (3rd IS) Assay (standardized to WHO 3rd International Standard, 81/565), Access TSH (3rd IS) Calibrators, and the Access Immunoassay analyzers comprise the Access Immunoassay System for the quantitative determination of thyroid-stimulating hormone (thyrotropin, TSH, hTSH) in human serum and plasma.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a medical device: "Access TSH (3rd IS) Assay and Access TSH (3rd IS) Calibrators on the Access Immunoassay Systems." This document primarily focuses on demonstrating substantial equivalence to a predicate device rather than presenting a study design and results against specific acceptance criteria for a novel AI/ML-driven diagnostic device.

Therefore, many of the typical acceptance criteria and study design elements requested in your prompt (e.g., sample sizes for training/test sets in AI/ML, number of experts for ground truth, MRMC studies, standalone algorithm performance) are not directly applicable or discussed in this type of submission. This document describes a traditional in-vitro diagnostic (IVD) assay, not an AI/ML device.

However, I can extract the closest equivalent information based on the provided text, interpreting "acceptance criteria" as performance specifications and "study" as the validation studies performed for this IVD device.

Acceptance Criteria and Reported Device Performance (Table)

While formal "acceptance criteria" are not presented as such for an AI/ML model, the document details various performance characteristics and their achieved results. The "Predicate" column can be seen as a de facto benchmark or comparison point for substantial equivalence.

Performance Characteristic	Acceptance Criteria (Implied/Predicate)	Reported Device Performance (Access TSH (3rd IS) Assay)
Method Comparison (vs. Predicate)	Slope: 0.95 ± 0.10 (specification)	Slope: 0.94 (95% CI: 0.92 to 0.97)
	Intercept: Not explicitly stated as criterion	Intercept: -0.02 µIU/mL
	Correlation Coefficient (r): Not explicitly stated as criterion	r = 0.99
Imprecision (Total CV)	≤ 10% CV for concentrations > 0.02 µIU/mL	3.1 to 6.3 %CV at all TSH concentrations
Imprecision (Total SD)	≤ 0.0029 SD at concentrations ≤ 0.02 µIU/mL	0.0008 to 0.0015 µIU/mL at TSH concentrations ≤ 0.02 µIU/mL
High-dose Hook Effect	No significant hook effect expected below high concentration	No high-dose hook effect up to at least 1,000 µIU/mL
Linearity	Linear across the assay range	Linear across 0.01 to approximately 50.0 µIU/mL
Dilution Recovery	Average recovery of 100 ± 10% for 10-fold dilution	Average recovery of 100 ± 10% when diluted 10-fold (50-500 µIU/mL)
Limit of Blank (LoB)	Not explicitly stated as criterion	< 0.005 µIU/mL
Limit of Detection (LoD)	Not explicitly stated as criterion	≤ 0.005 µIU/mL (95% probability)
Limit of Quantitation (LoQ)	Not explicitly stated as criterion	≤ 0.01 µIU/mL (between-run imprecision ≤ 10%)
Analytical Specificity (Interference)	No significant interference expected	No significant interference from total protein, bilirubin, hemoglobin, or triglycerides
Analytical Specificity (Cross-reactivity)	No significant cross-reactivity expected	No significant cross-reactivity from substances similar to hTSH
Matrix Comparison (Serum vs. Plasma)	Slope close to 1.00 (implied for equivalence)	Serum (no gel) vs. serum (gel): slope = 1.00 (CI 0.98-1.02)
		Plasma vs. serum (gel): slope = 1.00 (CI 0.98-1.01)
		Plasma vs. serum (no gel): slope = 1.00 (CI 0.98-1.03)

Study Details for the Access TSH (3rd IS) Assay:

Sample Size used for the Test Set and Data Provenance:
- Method Comparison: 155 serum samples.
- Imprecision: Not explicitly stated, but implies multiple replicates of various serum samples across TSH concentrations.
- High-dose Hook Effect: One serum sample tested up to 1,000 µIU/mL.
- Linearity & Dilution Recovery: Serum samples (quantity not specified for the overall study design of these tests, but likely multiple samples at various levels).
- LoB, LoD, LoQ: Serum samples (quantity not specified).
- Analytical Specificity: Serum samples (for interference), and two individual patient serum samples for cross-reactivity.
- Expected Reference Intervals:
  - General Population (non-pregnant females and males): 367 subjects.
  - Pregnant females - 1st Trimester: 318 subjects.
  - Pregnant females - 2nd Trimester: 362 subjects.
  - Pregnant females - 3rd Trimester: 335 subjects.
- Matrix Comparison: 79 matched sets of serum (gel and no gel) and plasma (lithium-heparin) samples.
- Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective. Given the nature of IVD studies, it's typically prospective collection for performance validation.
Number of Experts used to establish the Ground Truth for the Test Set and Qualifications of those Experts:
- Not applicable in the context of an IVD assay measuring an analyte concentration. The "ground truth" for TSH levels is established by the reference measurement procedure or the predicate device's measured values, rather than expert interpretation of images or other subjective data. For reference interval studies, the "ground truth" would be the clinical status (euthyroid, pregnant trimester) determined by a clinician, not an "expert."
Adjudication Method for the Test Set:
- Not applicable as this is a quantitative chemical assay, not an interpretative diagnostic device requiring human adjudication of results.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done:
- No. This type of study is relevant for AI/ML devices where human readers' performance is augmented by AI. This document pertains to an automated IVD assay.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The performance metrics (imprecision, linearity, LoD, etc.) are all measures of the device's standalone analytical performance without human intervention in the result generation. The "method comparison" compares the new device's output to the predicate device's output.
The type of ground truth used:
- Quantitative Reference Measurement: For analytical performance characteristics (e.g., limit of detection, linearity, imprecision), the ground truth is based on gravimetric/volumetric preparation of controls and calibrators, or comparison to a well-characterized predicate device (which itself has its own reference measurement traceabilities).
- Clinical Status: For the establishment of "Expected Reference Intervals," the ground truth is the clinical classification of the subjects (e.g., "apparently healthy, normal euthyroid," "pregnant females - 1st Trimester") presumably determined by medical assessment.
- WHO International Reference Preparations: The calibrators and assay are standardized to specific WHO International Reference Preparations (e.g., WHO 3rd International Reference Preparation Thyroid Stimulating Hormone, Human, NIBSC Coded 81/565). This is the ultimate "ground truth" for the quantitative value of TSH.
The sample size for the training set:
- Not applicable. This is an IVD assay, not an AI/ML device that requires a training set in the typical sense. The "training" for such a device occurs during its development and optimization, not as a distinct "training set" like in machine learning. The calibration process uses specific calibrator levels to generate a calibration curve.
How the ground truth for the training set was established:
- Not applicable for the same reason as above. The "ground truth" for calibration is derived from the assigned values of the WHO International Reference Preparations through the calibrators.

Summary

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS) in the USA. The logo features a stylized graphic of three human profiles facing right, arranged in a stacked formation. The profiles are connected by flowing lines, creating a sense of unity and continuity. The graphic is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

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

August 18, 2016

BECKMAN COULTER, INC. MICHAEL LORENZ, SENIOR ANALYST, REGULATORY AFFAIRS IMMUNODIAGNOSTIC DEVELOPMENT CENTER 1000 LAKE HAZELTINE DRIVE CHASKA MN 55318-1361

Re: K153651

Trade/Device Name: Access TSH (3rd IS) Assay and Access TSH (3rd IS) Calibrators on the Access Immunoassay Systems Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid stimulating hormone test system Regulatory Class: II Product Code: JLW, JIS Dated: July 11, 2016 Received: July 13, 2016

Dear Mr. Lorenz:

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

{1}------------------------------------------------

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 (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" (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 (800) 638-2041 or (301) 796-7100 or at its Internet address

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

Sincerely yours,

Stayce Beck -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

{2}------------------------------------------------

Indications for Use

510(k) Number (if known)

K153651

Device Name

Access TSH (3rd IS) Assay and Access TSH (3rd IS) Calibrators on the Access Immunoassay Systems

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

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

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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

{3}------------------------------------------------

Image /page/3/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red circle with two white curved lines inside, followed by the words "BECKMAN" and "COULTER" stacked on top of each other in black, sans-serif font. The logo is simple and modern, with a focus on the company name.

Immunodiagnostic Development Center 1000 Lake Hazeltine Drive Chaska, Minnesota 55318-1084

510(k) Summary K153651

Date Prepared: December 15, 2015 Date Updated: July 11, 2016 Date Updated: August 17, 2016

This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92(a)(1).

Submitter's Name and Address

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

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

Angela Kilian Alternate Contact:

(952) 368-1330 (952) 368-7610 (fax)

Device Name

Proprietary / Trade Name:	Access TSH (3rd IS) Assay and AccessTSH (3rd IS) Calibrators on the AccessImmunoassay Systems
Common Name:	Thyroid stimulating hormone assay
Classification Name:	Thyroid stimulating hormone test system(21 CFR 862.1690)Secondary Calibrator (21CFR 862.1150)

Predicate Device

Access HYPERsensitive hTSH assay and Access HYPERsensitive hTSH Calibrators Manufactured by Beckman Coulter, Inc.

{4}------------------------------------------------

Device Description

Intended Use

The Access TSH (3rd IS) Calibrators are intended to calibrate the Access TSH (3rd IS) assay for the quantitative determination of human thyroidstimulating hormone (thyrotropin, TSH, hTSH) levels in human serum and plasma using the Access Immunoassay Systems.

{5}------------------------------------------------

Parameter	Access TSH (3rd IS) Assay	Predicate AccessHYPERsensitive hTSH Assay
Intended use	The Access TSH (3rd IS) assayis a paramagnetic particle,chemiluminescentimmunoassay for thequantitative determination ofhuman thyroid-stimulatinghormone (thyrotropin, TSH,hTSH) levels in human serumand plasma using the AccessImmunoassay Systems. Thisassay is capable of providing3rd generation TSH results.	The Access HYPERsensitivehTSH assay is a paramagneticparticle, chemiluminescentimmunoassay for thequantitative determination ofhuman thyroid-stimulatinghormone (thyrotropin, hTSH)levels in human serum andplasma using the AccessImmunoassay Systems. Thisassay is capable of providing 3rdgeneration (HYPERsensitivehTSH( and/or 2nd generation(Fast hTSH) results.
AnalyteMeasured	Human thyroid-stimulatinghormone (thyrotropin, TSH,hTSH)	Human thyroid-stimulatinghormone (TSH, thyrotropin,hTSH)
Standardization	WHO 3rd InternationalReference Preparation ThyroidStimulating Hormone, Human(NIBSC Coded 81/565)	WHO 2nd InternationalReference Preparation ThyroidStimulating Hormone, Human(NIBSC Coded 80/558)
Technology	Sandwich immunoassay	Sandwich immunoassay
Format	Chemiluminescent	Chemiluminescent
Method	Automated	Automated
Calibration	Utilizes a stored calibrationcurve	Utilizes a stored calibrationcurve
Sample Type	Serum or plasma	Serum or plasma
Measuring Range	0.01 – 50.0 µIU/mL	0.01 – 100 µIU/mL
Stability	Stable at 2 to 10°C for 28 daysafter initial use	Stable at 2 to 10°C 28 daysafter initial use
Parameter	Access TSH (3rd IS)Calibrators	Predicate AccessHYPERsensitive hTSHCalibrators
Intended use	The Access TSH (3rd IS)Calibrators are intended tocalibrate the Access TSH (3rd IS)assay for the quantitativedetermination of human thyroid-stimulating hormone(thyrotropin, TSH, hTSH) levelsin human serum and plasmausing the Access ImmunoassaySystems.	The Access HYPERsensitivehTSH Calibrators are intended tocalibrate the Access TSH (3rd IS)assay for the quantitativedetermination of human thyroid-stimulating hormone (thyrotropin,TSH, hTSH) levels in humanserum and plasma using theAccess Immunoassay Systems.
Standardization	WHO 3rd International ReferencePreparation Thyroid StimulatingHormone, Human (NIBSCCoded 81/565)	WHO 2nd International ReferencePreparation Thyroid StimulatingHormone, Human (NIBSC Coded81/565)
Calibrator Levels	6 levels(0 $ \mu $ IU/mL, and approximately0.050, 0.30, 3.0, 15.0, and 50.0 $ \mu $ IU/mL)	6 levels(0 $ \mu $ IU/mL, and approximately 0.1,0.5, 4.0, 10.0, and 100.0 $ \mu $ IU/mL)
Calibrator Matrix	Bovine serum albumin	Bovine serum albumin
Calibration CurveStability	28 days	28 Days
Stability	Vials are stable at 2 to 10°C for90 days after initial use.	Vials are stable 2 to 10°C untilexpiration date stated on the label

Comparison of Technological Characteristics to the Predicate (Assay)

{6}------------------------------------------------

Comparison of Technological Characteristics to the Predicate

(Calibrators)

{7}------------------------------------------------

Summary of Studies

Method Comparison: A comparison of 155 serum samples with TSH concentrations ranging from approximately 0.010 to 50.0 µIU/mL were run on both the Access TSH (3rd IS) assay and the predicate Access HYPERsensitive hTSH assay. 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 = 0.94 with 95% confidence interval of 0.92 to 0.97, an intercept = - 0.02 µIU/mL and a correlation coefficient (r) = 0.99 and a slope specification 0.95 ± 0.10

Imprecision: Serum samples within-run imprecision ranged from 1.5 to 3.5 %CV, between-day imprecision ranged from 1.6 to 5.3 %CV, between-run imprecision ranged from 0.2 to 2.0 %CV, and total imprecision ranged from 3.1 to 6.3 %CV at all TSH concentrations. Serum samples within-run SD ranged from 0.0004 to 0.0007 µlU/mL, the between-day SD ranged from 0.0005 to 0.0012 µIU/mL, the between-run SD ranged from 0.0001 to 0.0004 µIU/mL, and the total SD ranged from 0.0008 to 0.0015 µIU/mL at TSH concentrations ≤ 0.02 µIU/mL. TThe TSH (3rd IS) assay exhibits total imprecision of less than or equal to 10% CV for concentrations greater than 0.02 µIU/mL and ≤ 0.0029 SD at concentrations ≤ 0.02 µIU/mL.

High-dose Hook Effect: The Access TSH (3rd IS) assay demonstrated no high-dose hook effect up to at least 1,000 µIU/mL in a serum sample.

Linearity: The Access TSH (3rd IS) assay has demonstrated to be linear across the range of the assay (0.01 to approximately 50.0 µIU/mL) in serum samples.

{8}------------------------------------------------

Dilution Recovery: The Access TSH (3rd IS) assay has been demonstrated to dilute recover across the range of the assay (0.01 to approximately 50 ulU/mL) in serum samples. Samples containing hTSH concentrations from approximately 50 µIU/mL to 500 µIU/mL can be diluted 10-fold with an average recovery of 100 ± 10%.

Limit of Blank (LoB): The highest measurement result observed with no analyte present in a serum sample is < 0.005 µIU/mL.

Limit of Detection (LoD): The lowest concentration of analyte in a serum sample that can be detected with a stated probability (95%) is ≤ 0.005 μIU/mL.

Limit of Quantitation (LoQ): The lowest concentration of analyte in serum samples with between run imprecision of ≤ 10% is ≤ 0.01 µIU/mL.

Analytical Specificity: There is no significant interference from total protein, bilirubin, hemoglobin, or triglycerides in serum samples. Additionally, substances similar in structure to hTSH, when added to two individual patient serum samples with approximate hTSH concentrations of 0.3 µIU/mL and 5.0 µIU/mL, showed no significant cross-reactivity.

{9}------------------------------------------------

Expected Reference Intervals: TSH concentrations were measured in human serum samples collected from apparently healthy, normal euthyroid male and non-pregnant female subjects and pregnant female populations, with approximately equal distribution across all three trimesters (as defined by the American Congress of Obstetricians and Gynecologists), using the Access TSH (3rd IS) assay in order to establish the central 97.5% reference interval (see table below).

	Sample	Median	Range	97.5% Reference Interval
Population	Size	(µIU/mL)	(µIU/mL)	(µIU/mL)
General Population(non-pregnant females and males)ages 21 and older	367	1.48	0.32 - 7.08	0.45 - 5.33
Pregnant females - 1st Trimester	318	1.13	0.009 - 5.89	0.05 - 3.70
Pregnant females - 2nd Trimester	362	1.47	0.028 - 5.78	0.31 - 4.35
Pregnant females - 3rd Trimester	335	1.61	0.27 - 10.25	0.41 - 5.18

Matrix Comparison: A comparison of seventy-nine (79) matched sets of serum (gel and no gel) and plasma (lithium-heparin) samples with TSH concentrations ranging from approximately 0.01 to 50 µlU/mL were compared using Passing-Bablok regression. The observed linear fit for serum (no gel) vs. serum (gel) had an estimated slope = 1.00 with a 95% confidence interval (CI) of 0.98 to 1.02. The observed linear fit for plasma vs. serum (gel) had an estimated slope =1.00 with a 95% Cl of 0.98 to 1.01. The observed linear fit for plasma vs. serum (no gel) had an estimated slope of 1.00, with a 95% Cl of 0.98 to 1.03.

{10}------------------------------------------------

Calibrators: The Access TSH (3rd IS) Calibrators are a six-level calibrator set intended to calibrate the Access TSH (3rd IS) assay for the quantitative determination of thyroid-stimulating hormone (thyrotropin, TSH, hTSH) levels in human serum and plasma using the Access Immunoassay Systems. The calibrator set provides calibrators at six levels - zero and approximately 0.050, 0.30, 3.0, 15.0, and 50.0 µlU/mL (mIU/L).

· Level S0; buffered bovine serum albumin matrix with surfactant, < 0.1% sodium azide, and 0.5% ProClin 300. Contains 0 ulU/mL (mIU/L) hTSH.
Levels S1 S5; approximately 0.05, 0.30, 3.0, 15.0, and 50.0 µIU/mL . (mIU/L), respectively, in buffered BSA matrix with surfactant, < 0.1% sodium azide, and 0.5% ProClin 300.

The Access TSH (3rd IS) Calibrator kit contains one vial of each calibrator level are contained in 2.5 mL vials. The calibrator vials are intended for storage at 2-10°C.

Calibration cards are provided with each calibrator kit. Calibration cards contain bar codes that are encrypted with the individual calibrator concentrations for each calibrator level.

The Access TSH (3d IS) Calibrators are standardized to the WHO 3rd International Reference Preparation Thyroid Stimulating Hormone, Human (NIBSC Coded 81/565).

Conclusion:

The Access TSH (3rd IS) Assay and Access TSH (3rd IS) Calibrators, for use on the Access Immunoassay Systems, are substantially equivalent to the predicate device, Access HYPERsensitive hTSH for the measurement of human TSH (thyrotropin, hTSH, TSH).

Regulation Number and Section

§ 862.1690 Thyroid stimulating hormone test system.

(a)
Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as thyrotrophin and thyrotrophic hormone, in serum and plasma. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.(b)
Classification. Class II.