The Nichols Institute Diagnostics Chemiluminescence Thyroglobulin is a two-site immunometric assay for the quantitative measurement of thyroglobulin in human serum. The assay is intended to aid in monitoring for the presence of local and metastatic thyroid tissue in patients who have had prior thyroidectorny (using surgery with or without radioiodine). This assay is also indicated for monitoring thyroglobulin levels in combination with radioiodine whole body scans after either rhTSH administration or thyroid hormone withdrawal for detecting presence of thyroid tissue in patients with well-differentiated thyroid cancer. The assay should only be used on patients who lack thyroglobulin autoantibodies.

Device Description

The Chemiluminescence Thyroglobulin kit has sufficient reagents for 100 tests. The throglobulin assay is a chemiluminescence sandwich immunoassay assay utilizing a biotinylated goat antiassay 1s a cheinnummicscented sunding monoclonal antibody labeled with acriding for detection. thyrogloutin for captare and a modio monomal and seprosilicate glass tube followed by the A U.200-IIL Serum Sample 1s added to a 12×10 uline and 0.050 mL of acridinium labeled antithyroglobulin reagents. Samples are also run at a 1/10 dilution (hook detection tube) to check for t thyroglountif teagents. Butiples are also in the assay. An avidin-coated bead is then added to the polentially mixture. The assay incubates at room temperature for 16-24 hours on top of a horizontal rotator set & 180 ± 10 rpm. Thyroglobulin in the serum sample binds to the biotinylated antibody and acridinium labeled antibody to form a sandwich-complex. Because of the high affinity between biotin and avidin, the captured sandwich complex binds to the avidin-coated bead. Free oetween brom and avidin, the capitaled antibody are separated from the complex bound to the bead by aspiration of the reaction mixture and subsequent washing. The tubes containing the washed beads are placed into a luminometer, which automatically injects Trigger 1 and 2, initiating the chemiluminescence reaction. The light is quantified by the luminometer and minating the onomianinessonts (RLU). The amount of acridinium labeled antibody bound is directly proportional to the concention of thyroglobulin in the sample. A log-log standard curve uncectly proportional to the concentration of the ordinate versus the respective concentration of each IS gelleration of proting the mount NFO shecissa. The concentration of thyroglobulin is determined directly from the standard curve.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The core of the acceptance criteria seems to be framed around demonstrating substantial equivalence to a predicate device and showing clinical utility for its intended use. While explicit numerical acceptance criteria for sensitivity, specificity, etc., weren't
fully specified as pre-defined targets in the document, the clinical study's results (especially in Table 3) serve as the evidence for meeting acceptable performance for market clearance.

Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied / Contextual)	Reported Device Performance (Nichols Tg ICMA)
Method Comparison (Against Predicate)
Agreement (<60 ng/mL)	High concordance with predicate device (Kronus OptiQuant Thyroglobulin kit)	93.8%
Agreement (≥60 ng/mL)	High concordance with predicate device (Kronus OptiQuant Thyroglobulin kit)	97.6%
Relative Sensitivity (Cut-off ≥5.0 ng/mL)	High relative sensitivity compared to predicate	99%
Relative Specificity (Cut-off <5.0 ng/mL)	High relative specificity compared to predicate	86%
Clinical Performance (Diagnostic Utility for Thyroid Cancer Monitoring)
Sensitivity (Combined rhTSH WBS + Tg ICMA)	Aid in monitoring for residual/recurrent thyroid tissue with high sensitivity	92% (when diagnostic standard was combined withdrawal WBS and/or withdrawal serum Tg ≥2.0 ng/mL)
Specificity (Combined rhTSH WBS + Tg ICMA)	Aid in monitoring for residual/recurrent thyroid tissue with high specificity	91% (when diagnostic standard was combined withdrawal WBS and/or withdrawal serum Tg ≥2.0 ng/mL)
Positive Predictive Value (PPV) (Combined rhTSH WBS + Tg ICMA)	High PPV for residual/recurrent thyroid tissue	96% (when diagnostic standard was combined withdrawal WBS and/or withdrawal serum Tg ≥2.0 ng/mL)
Negative Predictive Value (NPV) (Combined rhTSH WBS + Tg ICMA)	High NPV for exclusion of residual/recurrent thyroid tissue	82% (when diagnostic standard was combined withdrawal WBS and/or withdrawal serum Tg ≥2.0 ng/mL)
Accuracy (Combined rhTSH WBS + Tg ICMA)	High overall accuracy in detecting/excluding residual/recurrent thyroid tissue	92% (when diagnostic standard was combined withdrawal WBS and/or withdrawal serum Tg ≥2.0 ng/mL)
Sensitivity (Withdrawal Tg testing alone)	Good standalone sensitivity for identifying residual/recurrent thyroid tissue (for comparison)	88% (when diagnostic standard was combined withdrawal WBS and/or withdrawal serum Tg ≥2.0 ng/mL)
Specificity (Withdrawal Tg testing alone)	Good standalone specificity for identifying residual/recurrent thyroid tissue (for comparison)	100% (when diagnostic standard was combined withdrawal WBS and/or withdrawal serum Tg ≥2.0 ng/mL)

Study Details

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

Method Comparison Study (N=121):
- Sample Size: 121
- Data Provenance: Not explicitly stated, but likely from a clinical laboratory or reference lab given the NCCLS guidelines. It is
  retrospective, as samples were "assayed in parallel."
Clinical Performance Study (Haugen BR et al, 1999 JCEM):
- Sample Size: Up to 162 patients with eligible whole body scan results. Specific sub-cohorts are mentioned for various analyses (e.g., N=44 for THT baseline negative, N=117 for combined withdrawal Tg + WBS positive, etc.). All patients had negative thyroglobulin autoantibody results.
- Data Provenance: Retrospective – The samples were sourced from a published clinical study (Haugen BR et al, 1999 JCEM 84: 3877-3885), where permission was obtained to use the samples. The study involved patients with well-differentiated thyroid cancer. The country of origin is not explicitly stated, but Haugen's affiliations often suggest US-based research.

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

Method Comparison Study: Ground truth was established by the predicate device (Kronus OptiQuant™ Thyroglobulin kit) results. No human experts are described for establishing ground truth for this phase.
Clinical Performance Study: The ground truth was based on a "diagnostic standard" which combined clinical parameters including radioiodine whole body scans (WBS) and serum Tg measurements (from the initial study, which used a sensitive Tg radioimmunoassay (Tg RIA) and later the Nichols Tg ICMA). The interpretation of these diagnostic standards implies expert judgment (e.g., "positive withdrawal scan," "positive post-therapeutic scan," "radioiodine uptake was found outside the thyroid bed considered positive for metastatic disease"). However, the document does not specify the number or qualifications of experts who established these diagnostic standards for the original Haugen study.

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

The document does not describe an adjudication method like 2+1 or 3+1 by multiple readers/experts. The ground truth for the clinical performance study was derived from a diagnostic standard that combined WBS and Tg results, implying a clinical consensus or established diagnostic protocol, rather than an adjudication process between independent expert interpretations of the test results.

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, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is an in vitro diagnostic (IVD) assay (a blood test), not an AI-assisted diagnostic imaging or interpretation tool that typically involves human readers. The clinical study compares the performance of the assay (Nichols Chemiluminescence Thyroglobulin assay) under different clinical scenarios (e.g., rhTSH stimulation vs. thyroid hormone withdrawal), and in combination with WBS, against a defined diagnostic standard.

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

The Nichols Institute Diagnostics Chemiluminescence Thyroglobulin assay inherently operates as a "standalone" device in the sense that it provides a quantitative measurement of thyroglobulin. The results are then interpreted by clinicians. The clinical study did evaluate the performance of the "withdrawal serum Tg ICMA results alone" against the diagnostic standard, reporting a sensitivity of 88% and specificity of 100%. This represents its standalone diagnostic performance when not combined with WBS.

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

The ground truth for the clinical performance study was a "diagnostic standard" combining a positive withdrawal whole body scan (WBS) and/or a positive post-therapeutic scan or a serum Tg ICMA of 10 ng/mL or more (for THT baseline Tg results), or a positive withdrawal WBS result or a positive post-therapeutic WBS and/or a serum Tg ICMA of 2.0 ng/mL or more (for other situations). This is a composite ground truth based on clinical imaging (WBS) and laboratory results (Tg levels), interpreted within established clinical guidelines for identifying residual or recurrent thyroid tissue. It implicitly relies on expert interpretation of WBS and the clinical significance of Tg levels.

8. The sample size for the training set

The document does not provide information on a training set sample size. The study described is a performance evaluation of the already developed assay. For IVDs, "training set" typically refers to samples used during the assay's development and optimization, rather than a separate formal clinical training dataset as seen with machine learning algorithms.

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

As no training set is explicitly described in the context of this 510(k) summary, there is no information on how its ground truth was established. For IVD assays, ground truth for development samples would typically involve well-characterized patient samples with known clinical diagnoses or confirmed pathology, often collected in house or through commercial biobanks.

Summary

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510(k) Summary 11.0

This summary of safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Name of Manufacturer, Contact Person and Date Summary Prepared: 1.

Nichols Institute Diagnostics 33047 Calle Aviador San Juan Capistrano, CA 92675 Phone: 949-240-5260 FAX: 949-240-5313 Contact Person: Jimmy Wong, Manager Clinical and Technical Affairs Date Prepared: April 19, 2000

Device Name:

Device Name: Nichols Institute Diagnostics Chemiluminescence Thyroglobulin Common Name: Thyroglobulin Immunoassay Common Name: Tityroglobulin inimanoussa)
Classification Name:Reagent system for the determination of thyroglobulin in human serum.

Class II 3. Classification: Regulation Number: 866.6010 Product Code: MSW, Immunology

Kronus OptiQuant Thyroglobulin kit Predicate Device: 4.

Device Description: 5.

Intended Use: 6.

The Nichols Institute Diagnostic Chemiluminescence Thyroglobulin is a two-site immunometric The Neiners Institute Diegnood of thereglobulin in human serum. The assay is intended to assay for the qualitative for the presence of local and metastatic thyroid tissue in patients who have had prior thyroidectory (using surgery with or without radioiodine). This assay is also indicated for monitoring thyroglobulin levels in combination with radioiodine whole body scans after cations The administration or thyroid hormone withdrawal for detecting presence of thyroid tissue in patients with well-differentiated thyroid cancer. The assay should only be used on patients who lack thyroglobulin autoantibodies.

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The presence of autoantibodies against thyroglobulin (TgAb) can interfere with assays for thyroglobulin; hence, the TgAb status of the patient should be determined and reported. Thyroglobulin antibodies can be quantitated with the Nichols Chemiluminescence Thyroglobulin Autoantibodies kit (catalog 60-4185).

The concentration of thyroglobulin (Tg) in a given specimen determined with assays from different manufacturers can vary due to differences in assay methods, reagent specificity, and presence of thyroglobulin autoantibodies. The results reported by the laboratory to the physician must include the identity of the Tg assay used. Values obtained with different assay methods cannot be used interchangeably. If in the course of serially monitoring a patient, the assay method used for determining Tg levels is changed, additional sequential testing should be carried out to confirm baseline values.

7. Comparison to Predicate Device:

The Nichols Institute Diagnostics Chemiluminescence Thyroglobulin is substantially equivalent to another product in commercial distribution with similar intended use. We assert it is substantially equivalent to the Kronus OptiQuant™ Thyroglobulin kit. The following are similarities and differences for each product.

Method Comparison Study: One hundred twenty-one samples were assayed in parallel between the predicate method and the Nichols Tg assay following the NCCLS EP9-A guidelines. Concordance testing on the entire n=121 samples was performed.

NicholsTg (Y)	<5.0ng/mL	5.0-9.9ng/mL	10.0-29.9ng/mL	30.0-59.9ng/mL	≥60.0ng/mL
<5.0ng/mL	19	1	0	0	0
5.0-9.9ng/mL	3	8	0	0	0
10.0-29.9ng/mL	0	4	27	0	0
30.0-59.9ng/mL	0	0	6	7	1
≥60.0ng/mL	0	0	0	5	40

Kronus OptiQuant™ Thyroglobulin

Agreement for results less than 60 ng/mL = 93.8%

Agreement for results greater than 60 ng/mL = 97,6%

Relative sensitivity using a cut-off of 5.0 ng/mL or greater = 99%

Relative specificity using a cut-off of less than 5.0 ng/mL = 86%

Similarities:

Intended use for each kit is similar. That is, both assays are intended to monitor Tg levels in patients . after thyroid surgery (with or without radioiodine ablation). Both assays state interference due to thyroglobulin autoantibodies and give warning not to use the assay for patients with thyroglobulin autoantibodies.
. Both assays use specific antibodies to bind and capture thyroglobulin. Both assays use an immunometric approach to measure thyroglobulin in human sera.
Both assays are standardized to the same CRM4.57 Thyroglobulin Reference standard and use . lyophilized calibrators made from purified human thyroglobulin Both assays report results in the same units - ng/mL.

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. The reported expected values in normal healthy adult volunteers are similar for both assays. Using the Kronus Thyroglobulin assay, the reported reference range is 0-60 ng/mL. Using the Nichols Chemiluminescence Thyroglobulin, the reported reference range is 3.2-56.7 ng/mL.
. Both assays incubate overnight at room temperature.

Differences: The differences pertain to differences in immunoassay technology and do not affect the intended uses of each device.

Feature	Nichols ChemiluminescenceThyroglobulin	Kronus Optiquant™Thyroglobulin Kit
Sample Size	200 uL serum	100 uL serum
Detection Method	Acridinium-ester coupled tomonoclonal antibody to Tg;chemiluminescence technology	125I labeled to a monoclonalantibody to Tg
Solid Phase	Avidin-coated bead	Antibody coated tube
Reportable Range	0-100 ng/mL	0-500 ng/mL

Feature	Nichols ChemiluminescenceThyroglobulin	Kronus OptiQuant™Thyroglobulin Kit
Sensitivity	Analytical = 0.07 ng/mLFunctional = 0.5 ng/mL	Analytical = 0.2 ng/mLFunctional = 0.35 ng/mL
Intra-Assay Precision (%CV)	N=6; 3.6-6.4 %	N=2; 1.3-2.7 %
Inter-Assay Precision (%CV)	N=10; 3.6-22%	N=2; 5.2-9.9%
Recovery	N=3; 94.2-107.5%	N=4; 96.5-105.2%
Parallelism	N=5; 83-120%	N=4; 88.3-117.3%
High Dose Hook Claim	Up to 1,000 ng/mL	Up to 50,000 ng/mL
Specificity	TSH @5,000 uIU/mL = NDT3 @2,000 ug/dL = NDT4 @40 ug/dL = ND	Not reported
Interference Studies:[Percent recovery]	Hemoglobin @500 mg/dL = 93%Bilirubin @20 mg/dL = 98%Triglyceride @3694 mg/dL = 103%	Hemoglobin = not reportedBilirubin = not reportedTriglyceride = not reported

Comparison of Performance Characteristics:

8. Clinical Performance in Patients with Well-Differentiated Thyroid Carcinoma

Nichols Institute Diagnostics obtained permission to use the samples from a published clinical study (Haugen BR et al, 1999 JCEM 84: 3877-3885) that evaluated the use of rhTSH in patients with welldifferentiated thyroid cancer. The Tg assay results described in that study were derived from a sensitive Tg radioimmunoassay (Tg RIA). In that study, serum Tg measurements after rhTSH stimulation were evaluated for disease detection when used alone and in combination with radioiodine whole body scan (WBS). The same patient sample cohort used in the Haugen study was also measured using the Nichols Chemiluminescence Thyroglobulin assay (Tg ICMA). Serum Tg was measured while patients were on thyroid hormone therapy at baseline. They then received rhTSH administration (0.9 mg every 24 hours x2 or 0.9 mg every 72 hours x3) with serum Tg testing at 48-hours, and Tg testing plus WBS occurring 72hours after their final injection of rhTSH. Approximately two weeks after rhTSH administration, patients were then withdrawn from thyroid hormone therapy. While the patients were hypothyroid, serum Tg testing and WBS were again performed. The diagnostic utility of rhTSH administration can then be compared against the traditional combination of withdrawal serum Tg testing and WBS. Up to 162 patients with eligible whole body scan results were analyzed for disease detection using serum Tg ICMA results, with and without WBS, against a diagnostic standard. All n=162 had negative thyroglobulin antibody results.

The ranges of serum Tg ICMA results were determined for four situations during the protocol. First, serum Tg ICMA results at baseline was analyzed .gainst the diagnostic standard, when the patient

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was on thyroid hormone therapy (THT). Second, serum Tg ICMA results, 72 hours after final rhTSH administration, were analyzed against the diagnostic standard. [The 72-hour Tg ICMA results were chosen for analysis because it was determined that this time point provided essentially equivalent results to the 48hour Tg ICMA results.] Third, 72-hour serum Tg ICMA after final rhTSH WBS were combined and analyzed against the diagnostic standard. Fourth, withdrawal serum Tg ICMA results alone was analyzed against the diagnostic standard. We analyzed results using two different diagnostic standards. The first diagnostic standard was used for only THT (baseline) Tg results. This diagnostic standard, by definition, was a positive withdrawal scan and/or a positive post-therapeutic scan or a serum Tg ICMA of 10 ng/mL or more in the absence of a positive scan. The second diagnostic standard, by definition, was the combination of a positive withdrawal WBS and/or a withdrawal serum Tg ICMA of 2.0 ng/mL or more. A positive scan was considered positive for either thyroid remnant and/or disease recurrence. A withdrawal WBS result in which radioiodine uptake was found outside the thyroid bed was considered positive for metastatic disease. Table 1 shows the ranges of serum Tg ICMA levels for each situation on patients considered negative for thyroid tissue. Table 2 shows the ranges of serum Tg ICMA levels for each situation on patients considered positive for thyroid tissue.

Table 1: Percent distribution of serum Tg ICMA levels in patients considered negative for residual or recurrent thyroid tissue. Diagnostic standard was the combination of a withdrawal serum Tg ICMA <2.0 ng/mL and/or a negative withdrawal WBS.

	N	<1.0ng/mL	1.0-1.9ng/mL
THT (baseline)	44	98%	2%
Post 72-hr rhTSHadministration	45	100%	0
Post 72-hr rhTSHplus rhTSH WBS	42	100%	0
Combination ofwithdrawal Tg +WBS	46	74%	26%

Table 2: Percent distribution of serum Tg ICMA levels in patients considered positive for residual or recurrent thyroid tissue. When the patient was on THT, the diagnostic standard was a positive withdrawal WBS and/or a serum Tg ICMA of 10 ng/mL or more in the absence of a positive WBS. In the other situations, the diagnostic standard was a positive withdrawal WBS result or a positive post-therapeutic WBS and/or a serum Tg ICMA of 2.0 ng/mL or more.

	N	<1.0ng/mL	1.0-1.9ng/mL	2.0-4.9ng/mL	5.0-9.9ng/mL	10.0-29.9ng/mL	≥30ng/mL
THT (baseline)	48	0	0	17%	10%	19%	54%
Post 72-hr rhTSHadministration	83	0	0	14%	11%	27%	48%
Post 72-hr rhTSHplus rhTSH WBS	108	17%	7%	11%	8%	20%	37%
Combination ofwithdrawal Tg +WBS	117	12%	7%	9%	9%	17%	47%

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The diagnostic sensitivity and specificity, positive and negative predictive values, and the diagnostic accuracy of the Nichols Tg ICMA were determined from this study. The following formulas were used (Figure 3).

Figure 3
Sensitivity = $TP \div [TP + FN] x 100$
Specificity = $TN \div [TN + FP] x 100$
Positive Predictive Value (PPV) = $TP \div [TP + FP] x 100$
Negative Predictive Value (NPV) = $TN \div [TN + FN] x 100$
Accuracy = $[TP + TN] \div total x 100$
TP = true positive
FP = false positive
TN = true negative
FN = false negative

Traditionally, the hypothyroid WBS in combination with withdrawal Tg testing is superior to either test when used alone. We analyzed the above situations to this standard. Categorically, the receiver operator characteristic for the test is improved using the combination of both withdrawal WBS and serum Tg ICMA testing (Table 3). These results demonstrate the usefulness of combining both the WBS and Tg ICMA testing to improve diagnostic sensitivity and specificity. The diagnostic sensitivity of combined 72hour rhTSH Tg ICMA testing plus rhTSH WBS to the diagnostic standard was 92%. There were 42 truenegative results, with concordant negative 72-hr rhTSH scans and withdrawal WBS results. Serum Tg ICMA levels were all less than 2.0 ng/mL in these cases. The diagnostic specificity of a negative 72-hour rhTSH scan plus 72-hour Tg ICMA <2.0 ng/mL test to the diagnostic standard was 91% (Table 3). The withdrawal serum Tg ICMA results was also evaluated separately. The diagnostic sensitivity and specificity was 88% and 100%, respectively, when the test was used alone in this cohort.

Table 3: Receiver Operator Characteristics for Nichols Tg ICMA when diagnostic standard was the combined withdrawal WBS and/or a withdrawal serum Tg of 2.0 ng/mL or more.

	Sensitivity	Specificity	PPV	NPV	Accuracy
THT (baseline)	42%	98%	98%	40%	58%
Post 72-hr rhTSH administration	71%	98%	99%	57%	79%
Post 72-hr rhTSH plus rhTSH WBS	92%	91%	96%	82%	92%
Withdrawal Tg testing (alone)	88%	100%	100%	77%	91%

PPV = positive predictive value

NPV = negative predictive value

Conclusions: These data, which were provided to FDA, demonstrate safety and effectiveness of the Nichols Institute Diagnostics Chemiluminescence Thyroglobulin for the intended in vitro diagnostic use.

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Image /page/5/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES" in all caps. The text is in a bold, sans-serif font. The words are arranged on a single line and centered.

Image /page/5/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" arranged around the perimeter. Inside the circle is a stylized image of an eagle with three curved lines representing its wings.

MAY - 9 2000

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Jimmy Wong Manager, Clinical and Technical Affairs Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, California 92675

Re: K994140

Trade Name: Nichols Institute Diagnostics Chemiluminescence Thyroglobulin Regulatory Class: II Product Code: MSW Dated: March 10, 2000 Received: March 13, 2000

Dear Mr. Wong:

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 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A 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 regulation (21 CFR Part 820) and that, through periodic OS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. 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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Page 2

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" (21CFR 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/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

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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4.0 Indications For Use Statement

INDICATIONS FOR USE STATEMENT

510(k) Number: K994140

Nichols Institute Diagnostics Chemiluminescence Thyroglobulin Device Name:

Indications for Use Statement: The Nichols Institute Diagnostics Chemiluminescence Thyroglobulin is a two-site immunometric assay for the quantitative measurement of thyroglobulin in human serum. The assay is intended to aid in monitoring for the presence of local and metastatic thyroid tissue in patients who have had prior thyroidectorny (using surgery with or without radioiodine). This assay is also indicated for monitoring thyroglobulin levels in combination with radioiodine whole body scans after either rhTSH administration or thyroid hormone withdrawal for detecting presence of thyroid tissue in patients with well-differentiated thyroid cancer. The assay should only be used on patients who lack thyroglobulin autoantibodies.

The concentration of thyroglobulin (Tg) in a given specimen determined with assays from different manufacturers can vary due to difference in assay methods, reagent specificity, and presence of thyroglobulin autoantibodies. The results reported by the laboratory to the physician must include the identity of the Tg assay used. Values obtained with different assay methods cannot be used interchangeably. If in the course of serially monitoring a patient, the assay method used for determining Tg levels is changed, additional sequential testing should be carried out to confirm baseline values,

(Please Do Not Write Below This Line - Continue On Another Page If Needed)

Concurrence of CDRH, Office of Device Evaluation (ODE)

[Signature]

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	K94148

Prescription Use ✓(Per 21 CFR 801.109)	Or	Over-The-Counter Use(Optional Format 1-2-96)
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Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.