The Access Intact PTH assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of intact parathyroid hormone (parathyrin, PTH) levels in human serum and plasma using the Access Immunoassay Systems. It is indicated to aid in the differential diagnosis of hyperparathyroidism, hypoparathyroidism, or hypercalcemia of malignancy and can be used intraoperatively. Assay results should be used in conjunction with other clinical data to assist the clinician in making individual patient management decisions.

The Access Intact PTH Calibrators are intended to calibrate the Access Intact PTH assay for the quantitative determination of intact parathyroid hormone (parathyrin, PTH) levels in human serum and plasma using the Access Immunoassay Systems.

Device Description

The Access Intact PTH reagents, calibrators, and the Access Immunoassay Analyzers (Access, Access 2, Synchron LXi 725, UniCel DxC600i, and UniCel Dxl 800) comprise the Access Immunoassay Systems for the determination of intact parathyroid hormone (PTH) levels in human serum and plasma.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Access Intact PTH and Intact PTH Calibrators on the Access® Immunoassay Systems, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Study Type	Acceptance Criteria (Implied)	Reported Device Performance
Imprecision (CV%)	Not explicitly stated	Routine Mode: 2.8% to 6.4% CV (for 12-1400 pg/mL)
		Intraoperative Mode: 3.1% to 10.6% CV (for 12-1400 pg/mL)
Dilution Recovery (Linearity)	Not explicitly stated	Routine Mode: Mean % recovery 91% to 103%
		Intraoperative Mode: Mean % recovery 85% to 98%
Methods Comparison (Routine vs. Predicate)	Not explicitly stated	Range: 16-2627 pg/mL
		Intercept: -11.5 pg/mL
		Slope: 1.09
		Correlation Coefficient (r): 0.99
Methods Comparison (Routine vs. Intraoperative)	Not explicitly stated	Range: 13-2848 pg/mL
		Intercept: 9.69 pg/mL
		Slope: 0.94
		Correlation Coefficient (r): 1.00
Methods Comparison (Intraoperative vs. Predicate)	Not explicitly stated	Range: 8-2453 pg/mL
		Intercept: 0.13 pg/mL
		Slope: 0.87
		Correlation Coefficient (r): 1.00
Analytical Specificity	No significant interference	No significant interference from bilirubin, hemoglobin, human serum albumin, and triglycerides.
Stability (Reagents)	Not explicitly stated	28 days after opening
Stability (Calibrators)	Not explicitly stated	Single use only, calibration stable for 28 days
Clinical Reference Range	Not explicitly stated	12-88 pg/mL (95% non-parametric reference interval)

Note: The acceptance criteria are "implied" as specific thresholds were not explicitly stated in the 510(k) summary (e.g., "CV must be < X%"). The reported performance implicitly met the FDA's requirements for substantial equivalence.

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

Imprecision: Not explicitly stated, but concentrations ranged from 12 to 1400 pg/mL, suggesting multiple samples tested at different levels.
Dilution Recovery (Linearity): "Multiple dilutions of EDTA plasma samples" were analyzed. Specific number not provided.
Methods Comparison:
- Routine vs. Commercial Immunoassay: 500 values
- Routine vs. Intraoperative: 493 values
- Intraoperative vs. Commercial Immunoassay: 393 values
Analytical Specificity: Not explicitly stated, but tested for potential contaminants (bilirubin, hemoglobin, human serum albumin, and triglycerides).
Clinical Reference Range: 289 matched human EDTA plasma and serum samples.
Data Provenance: The document does not explicitly state the country of origin.
- For the clinical reference range, samples were collected during three time periods in two geographic latitudes, suggesting prospective collection for that specific study. Other analytical studies do not specify prospective or retrospective.

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

Not applicable. This is an in vitro diagnostic (IVD) device for quantitative measurement of a biomarker. The "ground truth" for the test set is established by the analytical method itself (e.g., reference method for comparison, known concentrations for dilution linearity, established analytical techniques for specificity and imprecision). No human experts are used to establish ground truth in the way they would for image interpretation or disease diagnosis. For the reference range study, specific criteria (normal serum calcium, creatinine, 25-hydroxyvitamin D) were used to select "apparently healthy" individuals, but the "ground truth" is the measured PTH level.

4. Adjudication method for the test set

Not applicable. As described above, this is an IVD device measuring a quantitative biomarker. Adjudication methods like 2+1 or 3+1 are typically used in studies involving subjective interpretation, such as imaging.

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 IVD assay. It does not involve human readers interpreting cases with or without AI assistance. The comparisons done were between the new device and predicate devices.

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

Yes, the studies described are for the standalone performance of the Access Intact PTH assay on the Access Immunoassay Systems. The device produces a quantitative measurement of PTH levels. Human involvement is limited to operating the instrument and interpreting the numerical result in a clinical context, not in directly improving the "algorithm's" performance.

7. The type of ground truth used

Imprecision & Dilution Recovery: The ground truth is the expected performance based on established analytical chemistry principles and the known characteristics of the samples (e.g., known concentrations, dilution factors).
Methods Comparison: The ground truth is the measurement obtained from a commercially available, legally marketed immunoassay system (predicate device).
Analytical Specificity: The ground truth is the known concentration of PTH in samples intentionally spiked with potential interferents.
Clinical Reference Range: The "ground truth" is the distribution of PTH levels in a rigorously selected population of "apparently healthy" individuals, with exclusion criteria based on other clinical markers (serum calcium, creatinine, 25-hydroxyvitamin D).

8. The sample size for the training set

Not applicable in the context of typical AI/ML device development. This is an IVD device developed using traditional analytical chemistry and immunoassay principles, not a machine learning algorithm that requires a "training set" in the same way. The development and optimization of the assay would involve various experiments and reagent formulations, but these are not referred to as "training sets" in the ML sense.

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

Not applicable for the reasons stated in point 8.

Summary

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510(k) SUMMARY

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.

The assigned 510(k) number is: K061190

Submitter's Name and Address

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952) 368-1383 Fax: (952) 368-7610 Contact: Valynda Machen

Date Prepared: August 15, 2006

Device Names

Proprietary Name:	Intact PTH and Intact PTH Calibrators on the Access® Immunoassay Systems
Common Name:	Parathyroid Hormone Test
Classification Name:	Radioimmunoassay, Parathyroid Hormone

Predicate Device(s)

Elecsys Parathyroid Hormone Test System Roche Diagnostics Corporation 9115 Hague Rd Indianapolis, IN 46250

510(k) Number: K992680

Immulite®/Immulite® 1000 Turbo Intact PTH Diagnostic Products Corporation Corporate Offices 5210 Pacific Concourse Drive Los Angeles, CA 90045-6900

510(k) Number: K053533

SEP 15 2006

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Device Description

Intended Use

Comparison of Technological Characteristics

Attribute	Roche Elecsys ParathyroidHormone Test System	Immulite/Immulite 1000 TurboIntact PTH	Access Intact PTH
IntendedUse	Immunoassay for the in vitroquantitative determination of intactparathyroid hormone in human serumand plasma for the differentialdiagnosis of hypercalcemia andhypocalcemia.	For in vitro diagnostic use with theIMMULITE and IMMULITE 1000Analyzers-for the quantitativemeasurement of intact parathyroidhormone (parathyrin, PTH) in EDTAplasma or serum. It is intended as anaid in the differential diagnosis ofhypercalcemia and hypocalcemiaand can be used intraoperatively.	The Access Intact PTHassay is a paramagneticparticle, chemiluminescentimmunoassay for thequantitative determinationof intact parathyroidhormone (parathyrin, PTH)levels in human serum andplasma using the AccessImmunoassay Systems. Itis indicated to aid in thedifferential diagnosis ofhyperparathyroidism,hypoparathyroidism, orhypercalcemia ofmalignancy and can beused intraoperatively.
AssayPrinciples	Electrochemiluminescenceimmunoassay employing thesandwich principle.	Solid phase, chemiluminescentimmunometric assay.	The Access Intact PTHassay is a two-siteimmunoenzymatic("sandwich") assay.
SolidSupport	Streptavidin coated microparticles.	Bead coated with affinity purified goatpolyclonal anti-PTH (44-84) antibody.	Paramagnetic particlescoated with goat anti-PTH.
DetectionSystem	Chemiluminescent emission.	Chemiluminescent emission.	Utilizes dioxetane-basedchemiluminescentsubstrate;Measures light productionfrom a chemiluminescentreaction.
Calibrator	2 point calibration and master curveprovided via the reagent barcode.	Intact PTH Adjustors (Low and High)of Iyophilized synthetic human intactPTH in a buffered matrix.	Six levels (0, ~10, ~60,~300, ~1500, and ~3500pg/mL) of synthetic PTHantigen in a bufferedprotein solution withpreservatives.

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Summary of Analytical Studies

Imprecision: Imprecision was tested for concentrations from approximately 12 to 1400 pg/mL. Total imprecision ranged from 2.8% to 6.4% CV for the routine mode and 3.1% to 10.6% CV for the intraoperative mode.

Dilution Recovery (Linearity): Multiple dilutions of EDTA plasma samples were analyzed in the routine mode and intraoperative modes. Mean % recovery ranged from 91% to 103% for the routine mode and 85% to 98% for the intraoperative mode.

Methods Comparison:

A comparison of 500 values using the Access Intact PTH assay routine mode and a commercially available immunoassay system gave the following statistical data using Deming calculations: Range of observations=16-2627 pg/mL, Intercept=-11.5 pg/mL, Slope=1.09, Correlation coefficient (r)=0.99.

A comparison of 493 values using the Access Intact PTH assay routine mode and the intraoperative mode on the Access Immunoassay system gave the following statistical data using Deming calculations: Range of observations=13-2848 pg/mL, Intercept=9.69 pg/mL, Slope=0.94, Correlation coefficient (r)=1.00.

A comparison of 393 values using the Access Intact PTH intraoperative mode and a commercially available immunoassay system gave the following statistical data using Deming calculations: Range of observations=8-2453 pg/mL, Intercept=0.13 pg/mL, Slope=0.87, Correlation coefficient (r)=1.00.

Analytical Specificity: There was no significant interference from potential sample contaminants (bilirubin, hemoglobin, human serum albumin, and triglycerides) in either the routine or intraoperative modes.

Stability: Intact PTH reagents are stable for 28 days after opening. Intact PTH calibrators are singe use only. The calibration is stable for 28 days.

Summary of Clinical Studies

To establish a reference range, PTH concentrations were measured in 289 matched human EDTA plasma and serum samples from apparently healthy male and female subjects aged 19-67 years. Because of significant seasonal variations of 25-hydroxyvitamin D, the samples were collected during three time periods in two geographic latitudes. Additional testing was performed to exclude individuals with abnormal serum calcium, creatinine or 25-hydroxyvitamin D. A 95% non-parametric reference interval of 12-88 pg/mL was determined. Routine and intraoperative mode reference intervals are equivalent.

Conclusion

Intact PTH and Intact PTH Calibrators on the Access Immunoassay Systems is substantially equivalent to the Roche Elecsys Parathyroid Hormone Test System and the Immulite/Immulite 1000 Turbo Intact PTH assay for the quantitative determination of intact PTH levels in human serum and plasma.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird with three stylized wing-like shapes.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

SEP 1 5 2006

K061190 Re:

Trade/Device Name: Access Intact PTH Assay Regulation Number: 21 CFR 862.1545 Regulation Name: Parathyroid hormone test system Regulatory Class: Class II Product Code: CEW, JIT Dated: August 14, 2006 Received: August 16, 2006

Dear Ms. Machen:

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) 276-0484. 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 (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Alberto G

Alberto Gutierrez, Ph.D. 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

510(k) Number (if known): ______k061190

Device Name: Access Intact PTH Assay

Indications For Use:

The Access Intact PTH assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of intact parathyroid hormone (parathyrin, PTH) levels in human serum and plasma using the Access Immunoassay Systems. It is indicated to aid in the differential diagnosis of inumanououroidism, hypoparathyroidism, or hypercalcemia of malignancy and can be used intraoperatively. Assay results should be used in conjunction with other clinical data to assist the clinician in making individual patient management decisions.

Prescription Use X (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)

Carol C. Benson
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

K061190

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Regulation Number and Section

§ 862.1545 Parathyroid hormone test system.

(a)
Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.(b)
Classification. Class II.