The IMMULITE® Anti-TG Ab Calibration Material (CVM) is for in vitro diagnostic use in the verification of callbration of the IMMULITE Anti-TG Ab assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.
The IMMULITE® Thyroglobulin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Thyroglobulin assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.
The IMMULITE® Anti-TPO Ab Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Anti-TPO Ab assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.

Device Description

The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTGCVM i contains human serum/ buffer matrix with preservatives. LTGCVM2, LTGCVM3 and LTGCVM4 contain low, intermediate and high levels of Anti-TG Ab respectively, in human serum/ buffer matrix matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTOCVM1 contains human serum/ buffer matrix with preservatives. LTOCVM2, LTOCVM3 and LTOCVM4 contain low, intermediate and high levels of Anti-TPO Ab respectively, in human serum/ buffer matrix matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTYCVM1 in horse serum matrix with preservatives. LTYCVM2. LTYCVM3 and LTYCVM4 contain low, intermediate and high levels of Thyroglobulin respectively, in horse serum matrix with preservatives.

AI/ML Overview

This document describes the acceptance criteria and supporting studies for three calibration verification materials (CVMs): IMMULITE® 2000 Anti-TG Ab, IMMULITE® 2000 Anti-TPO Ab, and IMMULITE® 2000 Thyroglobulin.

1. Table of Acceptance Criteria and Reported Device Performance

This information is derived from the "Stability Acceptance Criteria Summary" and "Expected Values/Reference Range" sections for each device.

IMMULITE® 2000 Anti-TG Ab Calibration Verification Material

Acceptance Criteria Category	Specific Criteria	Reported Device Performance	Comments
Stability (Part 1: Guideline)	Dose value stability CVM to fall between ±15% of the assigned dose.	Stable up to 7 years when stored refrigerated at 2-8°C prior to opening.	Study indicates device meets this criterion based on the given shelf-life.
Stability (Part 2: Review Limits)	Dose value of controls to be within 2SD of the control target value generated from the stability calibrator curve. (Used if Part 1 fails).	Not explicitly stated as a pass/fail condition in table format, but described as a review process. The stability study supports the 7-year shelf life under these criteria.	This is a secondary acceptance criterion for review, not a primary pass/fail for the table.
Expected Values/Reference Range	Guideline Range (95% confidence interval) for each CVM level established based on Target Mean and ± 2 Standard Deviation (SD).	Level 1: 0.00 ≤ 20.00 IU/mL Level 2 (50% CVM1): 36.8 IU/mL (SD not specified for this level) Level 2 (50% CVM2): No performance data provided. Level 3: 384 - 520 IU/mL (Target Mean 452, SD 34) Level 4: 2661 - 3600 IU/mL (Target Mean 3130, SD 234.75)	These ranges are considered guidelines, with laboratories needing to establish their own limits. Device performance is described as generating these target values and SDs.
Assay Range	20-3000 IU/mL	20-3000 IU/mL	The CVMs cover this range.

IMMULITE® 2000 Anti-TPO Ab Calibration Verification Material

Acceptance Criteria Category	Specific Criteria	Reported Device Performance	Comments
Stability (Part 1: Guideline)	Dose value stability CVM to fall between: ±25% of assigned dose for CVM level 2 ±15% of assigned dose for CVM levels 3 and 4	Stable up to 9 years when stored refrigerated at 2-8°C prior to opening.	Study indicates device meets this criterion based on the given shelf-life.
Stability (Part 2: Review Limits)	Dose value of controls to be within 2SD of the control target value generated from the stability calibrator curve. (Used if Part 1 fails).	Not explicitly stated as a pass/fail condition in table format, but described as a review process. The stability study supports the 9-year shelf life under these criteria.	This is a secondary acceptance criterion for review, not a primary pass/fail for the table.
Expected Values/Reference Range	Guideline Range (95% confidence interval) for each CVM level established based on Target Mean and ± 2 Standard Deviation (SD).	Level 1: ≤ 10.00 IU/mL Level 2: 27.3 - 40.9 IU/mL (Target Mean 34.1, SD 3.4) Level 3: 239 - 323 IU/mL (Target Mean 281, SD 21) Level 4: 808 - 1093 IU/mL (Target Mean 950, SD 71.25)	These ranges are considered guidelines, with laboratories needing to establish their own limits. Device performance is described as generating these target values and SDs.
Assay Range	10-1000 IU/mL	10-1000 IU/mL	The CVMs cover this range.

IMMULITE® 2000 Thyroglobulin Calibration Verification Material

Acceptance Criteria Category	Specific Criteria	Reported Device Performance	Comments
Stability (Part 1: Guideline)	Dose value stability CVM to fall between ±10% of the assigned dose.	Stable up to 6 years when stored refrigerated at 2-8°C prior to opening.	Study indicates device meets this criterion based on the given shelf-life.
Stability (Part 2: Review Limits)	Dose value of controls to be within 2SD of the control target value generated from the stability calibrator curve. (Used if Part 1 fails).	Not explicitly stated as a pass/fail condition in table format, but described as a review process. The stability study supports the 6-year shelf life under these criteria.	This is a secondary acceptance criterion for review, not a primary pass/fail for the table.
Expected Values/Reference Range	Guideline Range (95% confidence interval) for each CVM level established based on Target Mean and ± 2 Standard Deviation (SD).	Level 1: 0.00 ≤ 20.0 ng/mL Level 2: 8.10 - 10.1 ng/mL (Target Mean 9.10, SD 0.5) Level 3: 31.9 - 40.5 ng/mL (Target Mean 36.2, SD 2.15) Level 4: No Guideline Range provided (Target Mean 430, SD not specified) 70% CVM4: 259 - 343 ng/mL (Target Mean 301, SD 21)	These ranges are considered guidelines, with laboratories needing to establish their own limits. Device performance is described as generating these target values and SDs.
Assay Range	0.2-300 NG/mL	0.2-300 ng/mL	The CVMs cover this range.

Study Information for All Devices (IMMULITE® 2000 Anti-TG Ab, Anti-TPO Ab, and Thyroglobulin CVMs)

The studies described are primarily stability and value assignment studies to establish the shelf-life and assigned values of the Calibration Verification Materials.

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

The "test set" for performance evaluation consists of the replicates used to determine the CVMs' target values and assess their stability.

Sample Size: For each CVM (Anti-TG Ab, Anti-TPO Ab, Thyroglobulin), the CVMs were tested on 27 replicates in total, comprised of nine runs and three replicates per run.
Data Provenance: The data appears to be prospective as it involves controlled testing in a laboratory setting to assign values and assess stability over time. The origin of the patient samples used for validation is not specified (e.g., country of origin).

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

The concept of "experts" in the traditional sense (e.g., radiologists) is not applicable here as these are in-vitro diagnostic calibration materials. The "ground truth" or reference values are established through rigorous laboratory procedures and traceability to international standards.

Number of Experts: Not applicable in the context of expert consensus for diagnostic interpretation.
Qualifications of Experts: The ground truth is established through qualified technical staff and validated measurement procedures traceable to WHO International Reference Preparations or Certified Reference Materials (e.g., WHO 1st IRP 65/93 for Anti-TG Ab, WHO 15 IRP 66/387 for Anti-TPO Ab, and BCR 457 for Thyroglobulin).

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

Adjudication methods like 2+1 or 3+1 are typically used for subjective diagnostic interpretations by multiple readers. This is not applicable to the quantitative measurements performed for these CVMs.

Adjudication Method: Not applicable. The process involves calculating average values across multiple runs and instruments.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

MRMC studies involving human readers are designed for diagnostic interpretation tasks, which is not the function of these CVMs.

MRMC Study: No, a Multi-Reader Multi-Case comparative effectiveness study was not performed.

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

These devices are calibration verification materials for automated immunoassay systems. Their "standalone performance" is exactly what is tested: their ability to provide stable and accurate reference values when processed by the IMMULITE 2000 systems. The performance data presented (target means, SDs, and stability) represents the standalone performance of the CVMs in conjunction with the IMMULITE 2000 systems.

Standalone Performance: Yes, the described stability and value assignment studies represent the standalone performance of the CVMs when used with the IMMULITE 2000 systems.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth for these CVMs is based on traceability to international reference standards and rigorous value assignment procedures.

Type of Ground Truth:
- Traceability to International Standards:
  - IMMULITE® 2000 Anti-TG Ab CVMs are traceable to WHO 1st IRP 65/93.
  - IMMULITE® 2000 Anti-TPO Ab CVMs are traceable to WHO 15 IRP 66/387.
  - IMMULITE® 2000 Thyroglobulin CVMs are traceable to Certified Reference Material from human thyroglobulin (BCR 457).
- Value Assignment Procedure: The CVMs are manufactured using qualified materials and measurement procedures. Their dose values are generated using curves from assigned reference calibrators, which are themselves traceable to the international standards.

8. The Sample Size for the Training Set

The concept of a "training set" typically applies to machine learning algorithms. For these CVMs, the "training" equivalent would be the extensive manufacturing and internal calibration processes that establish the reference calibrators and assigned values.

Sample Size for Training Set: Not explicitly defined in terms of a "training set" like in AI/ML. However, the internal manufacturing and value assignment processes involve various calibrator lots and materials that indirectly serve this purpose. The document mentions "8 level Anti-TG Ab calibrators," "7 level Anti-TPO Ab calibrators," and "9 level Thyroglobulin calibrators" used internally during manufacture and release testing. These calibrators would form the basis for the "training" of the system's ability to measure the analytes.

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

Similar to point 8, the "ground truth for the training set" refers to the establishment of the reference for the internal calibrators that are used to assign values to these CVMs.

Ground Truth for Training Set: The ground truth for the internal reference calibrators is established through:
- Traceability to WHO International Reference Preparations or Certified Reference Materials: As detailed in point 7.
- Use of Qualified Materials and Measurement Procedures: The calibrators are prepared using specific antibody stocks (e.g., Anti-TG antibody stock, Anti-TPO antibody stock) and are carefully manufactured.
- Validation with Patient Samples and Controls: For value assignment validation, the documents state:
  - Anti-TG Ab: "Two levels of commercially available controls, and 30 patient samples (10 spiked normal patients samples, two patient samples and 18 spiked samples) are used to validate CVM value assignments."
  - Anti-TPO Ab: "Two levels of commercially available controls, and 30 patient samples and 25 spiked samples) are used to validate CVM value assignments."
  - Thyroglobulin: "Three levels of commercially available controls, and 30 patient samples (5 normal patients samples and 25 spiked samples) are used to validate CVM value assignments."

This indicates a thorough process of establishing reliable reference values for the materials.

Summary

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510(k) Summary

Introduction: According to the requirements of 21 CFR 807.92. the following information provides sufficient details to understand the basis for determination of substantial equivalence.

The assigned 510(k) Number: K132391

1. Submitter	Siemens Healthcare Diagnostics Inc.		SEP 2 0 2013
Mailing Address:	511 Benedict AvenueTarrytown, NY 10591
Contact Person:	Garo Mimaryan, MS, RACTechnical Regulatory Affairs Specialist III
Phone Number:	(914)-524-3270
Fax Number:	(914)-524-2101
E-mail Address:	garo.mimaryan@siemens.com
Date Prepared:	September 16, 2013
2. Device Name
Proprietary Name:	IMMULITE® 2000 Anti-TG Ab Calibration Verification Material
Measurand:	Quality Control materials for IMMULITE® 2000 Anti-TG assay
Type of Test:	Calibration Verification Material (CVM) for IMMULITE® 2000Anti-TG Ab assay
Regulation Section:	21 CFR 862.1660, Quality Control Material
Classification:	Class I Reserved
Products Code:	JJX – Single (Specified) Analyte Controls (Assayed andUnassayed)
Panel:	Clinical Chemistry (75)
3. Predicate Device Name	Elecsys Anti-TG CalCheck
Predicate 510(k) No:	K020369
4. Device Description:	The Calibration Verification Material (CVM) contains one set of

matrix with preservatives. LTGCVM2, LTGCVM3 and LTGCVM4 contain low, intermediate and high levels of Anti-TG Ab respectively, in human serum/ buffer matrix matrix with preservatives.

See Indications for Use Statement below The IMMULITE® Anti-TG Ab Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Anti-TG Ab assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.

four vials, 2 mL each. LTGCVM i contains human serum/ buffer

For prescription use only

IMMULITE® 2000 Systems

Special Conditions for Use Statement(s): Special Instrument Requirements:

Intended Use:

Indication for Use:

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6. Technological Characteristics and Substantial Equivalence Comparison with Predicate:

A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Anti-TG Ab Calibration Verification Material (CVM) is substantially equivalent to the predicate device, Elecsys Anti-TG CalCheck, as summarized in Table 1.

Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate Device	Predicate Device
	IMMULITE 2000 Anti-TG Ab CVM	Elecsys Anti-Tg CalCheck
IntendedUse	The IMMULITE® Anti-TG AbCalibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Anti-TG Ab assay on theIMMULITE 2000 systems as indicatedin the CVM Package Insert.	The Elecsys Anti-Tg CalCheck is foruse in the verification of thecalibration established by the ElecsysAnti-Tg reagent on the indicatedElecsys and cobas e immunoassayanalyzers.
Analyte	Anti-TG Ab	Anti-Tg
Form	Lyophilized	Lyophilized
Matrix	Human Serum	Human Serum
stability	Stable until the expiration date whenstored refrigerated.	Stable until the expiration date whenstored refrigerated.
Storage	2-8°C	2-8°C

	DIFFERENCES
	Candidate Device	Predicate Device
	IMMULITE 2000 Anti-TG Ab CVM	Elecsys Anti-Tg CalCheck
Levels	4	3
Use	Single Use Only	Not For Single Use

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.

Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Anti-TG Ab Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 Anti-TG Ab Calibration Verification Materials (CVMs) are stable up to 7 years when stored refrigerated at 2-8°C prior to opening.

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Stability Protocol Summary:

The CVM study protocols are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) and the dose value determined from the reference calibrator curve and is summarized in Table 2.

Table 2: Stability Protocol Summary

CVM Level	Time-Points
	(Days)
LTGCVM1	1	182	365	548
LTGCVM2	1	182	365	548
LTGCVM3	1	182	365	548
LTGCVM4	1	182	365	548

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE 2000 Anti-TG Ab Calibration Verification Material (CVM) consists of 2 parts. Part 1 consists of the Guideline Acceptance Criteria which requires the dose value stability CVM to fall between ±15% of the assigned dose. Part 2 consists of the Review Limits Acceptance Criteria which requires the dose value of the controls to be within 2SD of the control target value generated from the stability calibrator curve. If the result is not within the acceptable dose range of ±15%, then additional data review is performed using the part 2 acceptance criterion.

Traceability:

The IMMULITE® 2000 Anti-TG Ab CVMs are traceable to WHO 1st IRP 65/93. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE Anti-TG Ab (Anti-Thyroglobulin antibody) CVMs are 4 level materials which are a subset of 8 level Anti-TG Ab calibrators, Calibrators are not commercialized but are used internally during manufacture and release testing of Anti-TG Ab reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using Anti-TG antibody stock and are traceable to WHO 1ª IRP 65/93. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Two levels of commercially available controls, and 30 patient samples (10 spiked normal patients samples, two patient samples and 18 spiked samples) are used to validate CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of nine runs and three replicates per run on seven IMMULITE 2000 systems and five different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges

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Expected Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run. 5 different reagent kit lots and 7 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific value card. The expected assay range is 20 -3000 IU/mL. The target values in Table 3 can be considered as guidelines.

Table 3:		Target Values
----------	--	---------------

Analyte targetlevels	Level	Target Mean(IU/mL)	SD	Guideline ±2SD Range(IU/mL)
	1	0.00	-	0.00 ≤20.00
	2	73.5	-	-
	50% CVM1	36.8	2.75	31.3 42.3
	50% CVM2
	3	452	34	384 520
	4	3130	234.75	2661 3600
Assay Range		20-3000 IU/mL

Each laboratory should establish their limits for acceptability based on methodology, clinical significance and medical decision levels of the test analyte. The representative, total precision tabulated in the respective assay instructions for use may be considered as one factor when establishing local, acceptable ranges. The values provided above may be considered as guidelines. Value assignment is lot specific.

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents .
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic Calibrators
Guidance for Industry and FDA Staff Assayed and Unassayed Quality Control Material .

Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10

Conclusion: 9.

The IMMULITE® 2000 Anti-TG Ab (Anti-Thyroglobulin antibody) Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Elecsys Anti-Tg CalCheck. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device. Elecsys Anti-TG CalCheck, The IMMULITE® 2000 Anti-TG Ab Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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510(k) Summary

Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.

The assigned 510(k) Number: K132391

1. Submitter Mailing Address:
  Contact Person:

Phone Number: Fax Number: E-mail Address: Date Prepared:

1. Device Name Proprietary Name: Measurand: Type of Test:
  Regulation Section: Classification: Products Code:

Panel:

1. Predicate Device Name Predicate 510(k) No: 4. Device Description:

Intended Use:

Indication for Use:

Special Conditions for Use Statement(s): Special Instrument Requirements:

Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591

Garo Mimaryan, MS, RAC Technical Regulatory Affairs Specialist III (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com September 16, 2013

IMMULITE® 2000 Anti-TPO Ab Calibration Verification Material Quality Control materials for IMMULITE® 2000 Anti-TPO assay Calibration Verification Material (CVM) for IMMULITE® 2000 Anti-TPO Ab assay 21 CFR 862.1660. Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)

Elecsys Anti-TPO CalCheck K001014 The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTOCVM1 contains human serum/ buffer matrix with preservatives. LTOCVM2, LTOCVM3 and LTOCVM4 contain low, intermediate and high levels of Anti-TPO Ab respectively, in human serum/ buffer matrix matrix with preservatives.

See Indications for Use Statement below The IMMULITE® Anti-TPO Ab Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Anti-TPO Ab assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.

For prescription use only

IMMULITE® 2000 Systems

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A comparison of the device features, intended use, and other 6. Technological Characteristics information demonstrates that the IMMULITE® 2000 Anti-TPO` and Substantial Equivalence Ab Calibration Verification Material (CVM) is substantially Comparison with Predicate: equivalent to the predicate device, Elecsys Anti-TPO CalCheck, as summarized in Table 1.

SIMILARITIES
	Candidate Device	Predicate Device
	IMMULITE 2000 Anti-TPO Ab CVM	Elecsys Anti-TPO CalCheck
IntendedUse	The IMMULITE® Anti-TPO AbCalibration Verification Material (CVM)is for in vitro diagnostic use in theverification of calibration of theIMMULITE Anti-TPO Ab assay on theIMMULITE 2000 systems as indicatedin the CVM Package Insert.	The Elecsys Anti-TPO CalCheck isfor use in the verification of thecalibration established by the ElecsysAnti-TPO reagent on the indicatedElecsys and cobas e immunoassayanalyzers.
Analyte	Anti-TPO Ab	Anti-TPO
Form	Lyophilized	Lyophilized
Matrix	Human serum	Human serum
Stability	Stable until the expiration date whenstored refrigerated.	Stable until the expiration date whenstored refrigerated.
Storage	2-8°C	2-8°C

	Table 1: Substantial Equivalence Comparison

	DIFFERENCES
	Candidate Device	Predicate Device
	IMMULITE 2000 Anti-TPO Ab CVM	Elecsys Anti-TPO CalCheck
Levels	4	3
Use	Single Use Only	Not For Single Use

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.

Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Anti-TPO Ab Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 Anti-TPO Ab Calibration Verification Materials (CVMs) are stable up to 9 years when stored refrigerated at 2-8℃ prior to opening.

Stability Protocol Summary:

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CVM Level	Time-Points(Days)
LTOCVM1	1	2555	2920	3285
LTOCVM2	1	2555	2920	3285
LTOCVM3	1	2555	2920	3285
LTOCVM4	1	2555	2920	3285

Table 2: Stability Protocol Summary

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE 2000 Anti-TPO Ab Calibration Verification Material (CVM) consists of 2 parts. Part 1 consists of the Guideline Acceptance Criteria which requires the dose value stability CVM to fall between ±25% of the assigned dose for CVM level 2 and ±15% of assigned dose for CVM levels 3 and 4. Part 2 consists of the Review Limits Acceptance Criteria which requires the dose value of the controls to be within 2SD of the control target value generated from the stability calibrator curve. If the result is not within the acceptable dose range of £25% for level 2 and ±15% for levels 3 and 4, then additional data review is performed using the part 2 acceptance criterion.

Traceability:

The IMMULITE Anti-TPO Ab CVMs are traceable to WHO 15 IRP 66/387. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

Anti-TPO Ab (Anti-Thyroid Peroxidase Antibody) CVMs are 4 level materials which are a subset of 7 level Anti-TPO Ab calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Anti-TPO Ab reagents and two point adjustors. The assigned reference calibrators are prepared using Anti-TPO antibody stock and are traceable to WHO Ist IRP 66/387. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Two levels of commercially available controls, and 30 patient samples and 25 spiked samples) are used to validate CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of nine runs and three replicates per run on five IMMULITE 2000 systems and four different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges

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Expected Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run. 4 different reagent kit lots and 5 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific value card. The expected assay range is 10-1000 IU/mL .. The target values in Table 3 can be considered as guidelines.

Table 3: Target Values

Analyte targetlevels	Level	Target Mean(IU/mL)	SD	Guideline ±2SD Range(IU/mL)
	1	0.00	-	≤10.00
	2	34.1	3.4	27.3 40.9
	3	281	21	239 323
	4	950	71.25	808 1093
Assay Range	10 - 1000 IU/mL

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents .
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic Calibrators
Guidance for Industry and FDA Staff Assayed and Unassaved Quality Control Material .

Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10

9. Conclusion:

Anti-TPO Ab (Anti-Thyroid Peroxidase Antibody) Calibration Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Elecsys Anti-TPO CalCheck. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device. Elecsys Anti-TPO CalCheck. The IMMULITE® 2000 Anti-TPO Ab Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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510(k) Summary

According to the requirements of 21 CFR 807.92, the following information provides Introduction: sufficient details to understand the basis for determination of substantial equivalence.

The assigned 510(k) Number: K132391

1. Submitter Mailing Address:
  511 Benedict Avenue Tarrytown, NY 10591

Contact Person:

Phone Number: Fax Number: E-mail Address: Date Prepared:

Device Name Proprietary Name: Measurand: Type of Test:

Regulation Section: Classification: Products Code: Panel:

Predicate Device Name Predicate 510(k) No:
Device Description:

1. Intended Use: Indication for Use:
  Special Conditions for Use Statement(s): Special Instrument Requirements:

Garo Mimaryan, MS, RAC Technical Regulatory Affairs Specialist III (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com September 16, 2013

Siemens Healthcare Diagnostics Inc.

IMMULITE® 2000 Thyroglobulin Calibration Verification Material Quality Control materials for IMMULITE® 2000 Thyroglobulin assay Calibration Verification Material (CVM) for IMMULITE® 2000 Thyroglobulin assay 21 CFR 862.1660. Quality Control Material

Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)

ADVIA Centaur® Intact PTH Master Curve Material (MCM) K020217

The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTYCVM1 in horse serum matrix with preservatives. LTYCVM2. LTYCVM3 and LTYCVM4 contain low, intermediate and high levels of Thyroglobulin respectively, in horse serum matrix with preservatives.

See Indications for Use Statement below The IMMULITE® Thyroglobulin Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Thyroglobulin assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.

For prescription use only

IMMULITE® 2000 Systems

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

A comparison of the device features, intended use, and other 6. Technological Characteristics and Substantial Equivalence information demonstrates that the IMMULITE® 2000 Thyroglobulin Calibration Verification Material (CVM) is Comparison with Predicate: substantially equivalent to the predicate device, ADVIA Centaur® Intact PTH Master Curve Material, as summarized in Table 1.

Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate Device	Predicate Device
	IMMULITE® 2000 ThyroglobulinCalibration Verification Material	ADVIA Centaur® Intact PTHMaster Curve Material
IntendedUse	The IMMULITE® ThyroglobulinCalibration Verification Material (CVM) isfor in vitro diagnostic use in the verificationof calibration of the IMMULITEThyroglobulin assay on the IMMULITE2000 systems as indicated in the CVMPackage Insert.	For in vitro diagnostic use forevaluating the ADVIA Centaur®Intact PTH assays. This material isintended to be run singly asunknown samples after a two-pointcalibration has been performed onthe system.
Form	Lyophilized	Lyophilized
Matrix	Equine Serum	Equine Serum
Use	Single Use Only	Single Use Only

	DIFFERENCES
	Candidate Device	Predicate Device
	IMMULITE 2000 ThyroglobulinCalibration Verification Material(CVM)	ADVIA Centaur® Intact PTHMaster Curve Material (MCM)
Analyte	Thyroglobulin	Intact PTH
Levels	4	7
Stability	Stable until the expiration date whenstored refrigerated.	Stable until the expiration datewhen stored frozen.
Storage	2-8°C	-20°C

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.

Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Thyroglobulin Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 Thyroglobulin Calibration Verification Materials (CVMs) are stable up to 6 years when stored refrigerated at 2-8℃ prior to opening.

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Stability Protocol Summary:

Table 2: Stability Protocol Summary

CVM Level	Time-Points(Days)
LTYCVM1	1	1825	2190	3285
LTYCVM2	1	1825	2190	3285
LTYCVM3	1	1825	2190	3285
LTYCVM4	1	1825	2190	3285

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE 2000 Anti-TG Ab Calibration Verification Material (CVM) consists of 2 parts. Part 1 consists of the Guideline Acceptance Criteria which requires the dose value stability CVM to fall between ±10%. Part 2 consists of the Review Limits Acceptance Criteria which requires the dose value of the controls to be within 2SD of the control target value generated from the stability calibrator curve. If the result is not within the acceptable dose range of ±10%, then additional data review is performed using the part 2 acceptance criterion.

Traceability:

The IMMULITE Thyroglobulin CVMs are traceable to Certified Reference Material from human thyroglobulin (BCR 457) in terms of the Institute of Reference Materials and Measurements of the European Commission (formerly the Community Bureau of Reference. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

Thyroglobulin CVMs are 4 level materials which are a subset of 9 level Thyroglobulin calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Thyroglobulin reagents and two point adjustors. The IMMULITE Thyroglobulin CVMs are traceable to Certified Reference Material from human thyroglobulin (BCR 457) in terms of the Institute of Reference Materials and Measurements of the European Commission (formerly the Community Bureau of Reference. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Three levels of commercially available controls, and 30 patient samples (5 normal patients samples and 25 spiked samples) are used to validate CVM value assignments.

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The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of nine runs and three replicates per run on four IMMULITE 2000 systems and four different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges

Expected Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run. 4 different reagent kit lots and 4 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific value card. The expected assay range is 02-300 NG/mL. The target values in Table 3 can be considered as guidelines.

Analyte targetlevels	Level	Target Mean(ng/mL)	SD	Guideline ±2SD Range(ng/mL)
	1	0.00		0.00	≤20.0
	2	9.10	0.5	8.10	10.1
	3	36.2	2.15	31.9	40.5
	4	430	-	-	-
	30% CVM1
	70% CVM4	301	21	259	343
Assay Range	0.2 -300 ng/mL

Table 3: Target Values

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents .
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic ● Calibrators
Guidance for Industry and FDA Staff Assayed and Unassayed Quality Control Material .

Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10

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siemens

9. Conclusion:

Thyroglobulin Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed ADVIA Centaur® Intact PTH Master Curve Material. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, ADVIA Centaur® Intact PTH Master Curve Material, The IMMULITE® 2000 Thyroglobulin Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/13/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle.

Public Health Service

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

September 20, 2013

SIEMENS HEALTHCARE DIAGNOSTICS, INC. C/O MR. GARO MIMARYAN TECHNICAL REGULATORY AFFAIRS SPECIALIST III 511 BENEDICT AVENUE TARRYTOWN. NY 10591-5097

Re: K132391

Trade/Device Name: IMMULITE® 2000 Anti-TG Ab Calibration Verification Material; IMMULITE® 2000 Anti-TPO Ab Calibration Verification Material; IMMULITE® 2000 Thyroglobulin Calibration Verification Material; Regulation Number: 21 CFR 862.1660

Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I Reserved Product Code: JJX Dated: July 31, 2013 Received: August 1. 2013

Dear Mr. Mimaryan:

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

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Page 2-Mr. Mimaryan

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

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Maria M. Chan -S

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration -

Indications for Use

510(k) Number (if known) K 13239 l :

Device Name

IMMULITE® 2000 Anti-TG Ab Calibration Verification Material

Indications for Use (Describe)

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

[X] Prescription Use (Part 21 CFR 801 Subpart D)

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

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Maria M. Chan -S

Image /page/15/Picture/18 description: The image shows a logo with the letters FDA. The letters are stylized and appear to be outlined. The logo is simple and monochromatic.

FORM FDA 3881 (9/13)

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

PSC Publishing Services (301) 343-6740 EF

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K 132391

Device Name

IMMULITE® 2000 Thyroglobulin Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® Thyroglobulin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Thyroglobulin assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.

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

[x] Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 807 Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Maria M. Chan -

Image /page/16/Picture/18 description: The image shows the logo for the Food and Drug Administration (FDA). The logo is in black and white and features the letters "FDA" in a stylized font. The letters are bold and have a slightly rounded appearance. The logo is simple and recognizable, and it is often used on products that have been approved by the FDA.

FORM FDA 3881 (6/13)

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K132391

Device Name

IMMULITE® 2000 Anti-TPO Ab Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® Anti-TPO Ab Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Anti-TPO Ab assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.

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

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 807 Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Maria M. Chan -S

FDA

FORM FDA 3881 (6/13)

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.