For in vitro diagnostic use with the IMMULITE and IMMULITE 1000 Analyzers - for the quantitative measurement of intact parathyroid hormone (parathyrin, PTH) in EDTA plasma or serum. It is intended as an aid in the differential diagnosis of hypercalcemia and hypocalcemia and can be used intraoperatively.

Device Description

IMMULITE/IMMULITE 1000 Turbo Intact PTH is a solid-phase, chemiluminescent immunometric assay employing a goat polyclonal anti-PTH (44-84) antibody as the capture antibody and a goat polyclonal anti-PTH (1-34) antibody conjugated to alkaline phosphatase as the detection antibody.

AI/ML Overview

Here's an analysis of the IMMULITE®/IMMULITE® 1000 Turbo Intact PTH device's acceptance criteria and the supporting studies:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Used as a benchmark for intraoperative utility)	Reported Device Performance
Criterion 1: 50% or greater decrease from baseline PTH value suggests complete tumor removal.	Mayo Clinic Study: 45 out of 47 patients (96%) had their plasma intact PTH (iPTH) levels decrease to < 25% of baseline (exceeding the 50% threshold). Washington University Study: 46 out of 49 patients had a > 50% decrease in iPTH values.
Criterion 2: Return to normal iPTH values after parathyroid tissue is removed (indicating clinical cure).	Mayo Clinic Study: This occurred in 87% of patients, and all of them were clinically cured.
Criterion 3: Samples suitable for intraoperative monitoring (rapid results).	Mayo Clinic Study: Collection of blood samples was stopped at 10 minutes (2 patients) and 15 minutes (2 patients), suggesting results were available quickly enough for intraoperative decisions.
Criterion 4: Comparable physiological outcomes (normocalcemia postoperatively) when using intraoperative PTH vs. traditional methods.	Washington University Study: 44/49 (90%) of the study group (with intraoperative PTH) and 49/55 (89%) of the control group achieved normocalcemia postoperatively. This indicates identical physiological outcomes.
Criterion 5: Reduced reliance on frozen section use with intraoperative PTH.	Washington University Study: Frozen section use in the study group was statistically significantly less (p<0.0001) than in the control group.
Overall Conclusion from Studies: Assay provides surgeons with rapid, accurate results corresponding to clinical signs and outcomes.	The studies' findings support this conclusion, demonstrating the assay's utility, speed, and agreement with clinical outcomes.

2. Sample Size Used for the Test Set and Data Provenance

Mayo Clinic Study: 47 parathyroid gland surgery patients.
Washington University/Barnes Jewish Hospital Study:
- Study Group (with intraoperative PTH): 49 patients.
- Control Group (without intraoperative PTH): 55 patients.
Data Provenance: Retrospective, as the device was previously cleared (K992105) and these studies compared the already available device's performance to clinical data. The studies were conducted in the US (Mayo Clinic, Rochester, Minnesota and Washington University School of Medicine/Barnes Jewish Hospital, St. Louis, Missouri).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

The document does not explicitly state the number or specific qualifications of experts establishing the ground truth for the test set in terms of individual review of each case.

However, the "ground truth" for the device's efficacy in the clinical studies was implicitly established through:

Clinical outcomes: "clinically cured," "achieved normocalcemia postoperatively." This implies assessment by treating physicians/surgeons, likely qualified in endocrinology and/or surgery, whose consensus on patient's post-operative status served as a form of ground truth.
"Generally accepted guideline": The 50% decrease in PTH from baseline is a widely accepted clinical guideline in parathyroid surgery, implying a collective expert consensus within the medical community.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (like 2+1 or 3+1) for establishing ground truth from multiple experts for each patient's outcome. Instead, it relies on:

Clinical outcomes: The patients' actual post-operative clinical status (e.g., cure, normocalcemia) determined by their treating medical teams.
Established clinical guidelines: The 50% PTH decrease rule, which is a pre-defined and widely accepted criterion.

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

This involves an in vitro diagnostic (IVD) assay, not an AI-powered image analysis device or a system requiring human "readers" in the context of interpreting AI output. Therefore, an MRMC study is not applicable, and no effect size for human improvement with "AI assistance" is provided or relevant. The "assistance" here is a rapid laboratory test providing objective numbers to the surgeon.

The Washington University study did compare a group of patients receiving intraoperative PTH determinations (the device's output) to a control group that did not. This isn't an "AI assistance" scenario, but rather a direct comparison of a surgical workflow with and without the device. The "effect size" in this context could be viewed as:

Identical physiological outcomes: 90% vs 89% normocalcemia (indicating no negative impact and equivalent success).
Reduced frozen section use: Statistically significantly less (p<0.0001) in the study group, demonstrating a positive impact on surgical efficiency/practice.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the device is a standalone in vitro diagnostic assay. It measures PTH levels and provides a quantitative result. There is no "human-in-the-loop" performance in terms of interpreting algorithmic output for diagnosis in the way one would for an AI imaging device. The device itself performs the measurement, and the quantitative result is then used by the surgeon in conjunction with clinical guidelines.

7. The Type of Ground Truth Used

The ground truth used in these studies was primarily:

Clinical outcomes/follow-up Data: Post-operative clinical cure, achievement of normocalcemia, and the efficacy of the surgery.
Expert Consensus/Established Guidelines: The "generally accepted guideline that a 50% or greater decrease from the baseline PTH value suggests complete tumor removal."

8. The Sample Size for the Training Set

The document states that the IMMULITE/IMMULITE 1000 Turbo Intact PTH assay kit has not changed from its original FDA clearance on July 6, 1999 (K992105). This 510(k) is for demonstrating performance equivalence for a specific intraoperative use of an already cleared device.

Therefore, there isn't a "training set" in the context of developing a new algorithm or model for this 510(k) submission. The initial development and validation of the assay (which would involve a "training set" to establish its analytical characteristics like precision, linearity, etc.) would have occurred prior to its original 1999 clearance. The studies presented here are validation studies for a specific use case of an already established and cleared device.

9. How the Ground Truth for the Training Set Was Established

Since this 510(k) pertains to a specific use of an already cleared device, the concept of a "training set" for this submission is not directly applicable.

For the original development of the IMMULITE/IMMULITE 1000 Turbo Intact PTH assay (prior to K992105), the ground truth for establishing its analytical performance (e.g., accuracy, precision, linearity) would have been established through:

Reference Methods: Comparison to established standard methods or reference assays for measuring PTH.
Known Concentrations: Testing samples with known, spiked concentrations of PTH.
Clinical Correlation: Initial studies correlating assay results with clinical diagnoses and outcomes to validate its diagnostic utility.

However, these details are not provided in the given document, as it focuses on demonstrating equivalence for a new indication of use for an existing device.

Summary

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SUMMARY OF SAFETY AND EFFECTIVENESS

FEB 3 2006

Assigned 510(k) Number

The assigned 510(k) number is K053533

Sponsor Name and Address

Diagnostic Products Corporation Corporate Offices 5210 Pacific Concourse Drive Los Angeles, CA 90045-6900 (310) 645-8200

Contact

Deborah L. Morris Director, Clinical and Regulatory Affairs (310) 645-8200 extension 7426 dmorris@dpconline.com

Device Name

Trade Name: Common Name: Classification: DPC Catalog Number: IMMULITE®/IMMULITE® 1000 Turbo Intact PTH Intact Parathyroid Hormone Assay Class II device, CEW 21 CFR 862.1545 LSKPTZ (50 tests)

Description of Device

Indications for Use

"For in vitro diagnostic use with the IMMULITE and IMMULITE 1000 Analyzers - for the quantitative measurement of intact parathyroid hormone (parathyrin, PTH) in EDTA plasma or serum. It is intended as an aid in the differential diagnosis of hypercalcemia and hypocalcemia and can be used intraoperatively."

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Manufacturing Site

IMMULITE® IMMULITE® 1000 Turbo Intact PTH assay is manufactured by Diagnostic Products Corporation at the following locations:

Diagnostic Products Corporation Reagent Manufacturing Division 5700 West 96th Street Los Angeles, CA 90045-5597 FDA Establishment #: 2017183

Diagnostic Products Corporation Corporate Offices 5210 Pacific Concourse Drive Los Angeles, CA 90045-6900 FDA Establishment #: 3005250747

Performance Equivalence

Substantial equivalence assessment for intra-operative use of the IMMULITE/IMMULITE 1000 Turbo Intact PTH assay is based upon comparison to clinical data. The IMMULITE/IMMULITE 1000 Turbo Intact PTH assay kit has not changed from its original FDA clearance on July 6, 1999 (K992105). The IMMULITE/IMMULITE 1000 Turbo Intact PTH assay results were compared to clinical data when patient samples were tested in the IMMULITE/IMMULITE 1000 Turbo assay and results reported during parathyroid surgery. This comparison to clinical data was performed by two groups of researchers, Kao PC, et al. at the Mayo Clinic, Rochester Minnesota and Johnson LR, et al. at Washington University School of Medicine/Barnes Jewish Hospital, St. Louis, Missouri. Results were reported in peer reviewed journals.

Kao PC, van Heerden JA, Farley DR, et al. Intraoperative monitoring of parathyroid hormone with a rapid automated assay that is commerciallv available. Annal of Clin & Lab Science 2002;32(3):244-251.

Johnson LR, Doherty G, Lairmore T, et al. Evaluation of the performance and clinical impact of a rapid intraoperative parathyroid hormone assay in conjunction with preoperative imaging and concise parathyroidectomy. Clin Chem 2001:47(5):919-925.

Summary of Clinical Investigations

Clinical investigations using the IMMULITE/IMMULITE 1000 Turbo Intact PTH (parathyroid hormone) assay during parathyroid surgery were conducted by two groups of researchers, one at the Mayo Clinic, Rochester, Minnesota (Kao PC, et al.) and the second at University of Washington Medical School/Barnes Jewish Hospital, St. Louis Missouri (Johnson LR, et al.).

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The researchers at the Mayo Clinic collected blood specimens from 47 parathryroid gland surgery patients during surgery. The schedule for specimen collection was at baseline (prior to removal of abnormal tissue) and 5, 10, and 20 minutes after beginning parathyroid resection. The generally accepted guideline that a 50% or greater decrease from the baseline PTH value suggests complete tumor removal was used. Among 47 parathyroidectomy patients tested with the IMMULITE 1000 Turbo Intact PTH assay, 45 (96%) had their plasma intact PTH (iPTH) levels decrease to < 25% of baseline. A second criterion important for the surgeon is a return to normal iPTH values after parathyroid tissue is removed. This occurred in 87% of patients in this study and all of them were clinically cured. Collection of blood samples was stopped at 10 minutes in 2 patients and at 15 minutes in 2 patients making this test suitable for the intended intraoperative monitoring purpose.

The researchers at Washington University/Barnes Jewish Hospital examined the performance of the IMMULITE/IMMULITE 1000 Turbo iPTH assay intraoperatively in a study group of 49 patients and compared clinical outcomes to a "control" group of 55 patients that underwent parathyroidectomies without intraoperative PTH determinations. This study also employed the generally accepted guideline that a ≥50% decrease in the iPTH value from baseline suggests complete tumor removal. Samples were drawn in the operating room before incision and during the period 10-12 minutes after excision of suspected diseased parathyroid gland tissue. Of the 49 patients in the study group, 46 had a > 50% decrease in iPTH values within the first three post-resection samples. When the control and study groups with similar sex, age, and diagnoses were compared, 44/49 (90%) of the patients in the study group and 49/55 (89%) of the control patients achieved normocalcemia postoperatively. Thus, the surgery guided by intraoperative IMMULITE/MMULITE Turbo Intact PTH measurements had identical physiologic outcomes. Frozen section use in the study group was statistically significantly less (p<0.0001) than in the control group.

Conclusions from Clinical Studies

When used intraoperatively (samples tested and results reported) for parathyroid surgery, the IMMULITE/IMMULITE 1000 Turbo Intact PTH assay provides surgeons with rapid, accurate results corresponding to clinical signs and outcomes. The assay met the generally accepted criterion of a > 50% decrease from baseline (before incision) with complete tumor removal.

IMMULITE/IMMULITE 1000 Turbo Intact PTH assay's performance including measuring range, precision, analytical sensitivity, and correspondence to clinical status, makes this test suitable for the intended intraoperative monitoring purpose.

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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 stylized caduceus symbol, which is a staff with two snakes coiled around it. The symbol is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement. The text is in all capital letters and is evenly spaced around the symbol.

Public Health Service

FEB 3 2006 Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Deborah L. Morris Director, Clinical and Regulatory Affairs Diagnostic Products Corporation 5210 Pacific Concourse Drive Los Angeles, CA 90045

Re: K053533 Trade/Device Name: IMMULITE®/IMMULITE® 1000 Turbo Intact PTH Regulation Number: 21 CFR& 1545 Regulation Name: Parathyroid hormone test system Regulatory Class: Class II Product Code: CEW Dated: December 16, 2005 Received: December 20, 2005

Dear Ms. Morris:

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, pour 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 Gutierrez, Ph.D.

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):

IMMULITE®/IMMULITE® 1000 Turbo Intact PTH Device Name:

Indications For Use:

"For in vitro diagnostic use with the IMMULITE and IMMULITE 1000 Analyzers — for the quantitative measurement of intact parathyroid hormone (parathyrin, PTH) in EDTA plasma or serum. It is intended as an aid in the differential diagnosis of hypercalcemia and hypocalcemia and can be used intraoperatively."

Prescription Use

AND/OR

Over-The-Counter Use

(Part 21 CFR 801 Subpart D)

(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)

Alan Chappell
Vision Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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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.