K Number
K141444

Validate with FDA (Live)

Date Cleared
2014-07-09

(37 days)

Product Code
Regulation Number
862.1660
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The IMMULITE® Cortisol Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Cortisol assay on the IMMULITE 2000 systems.

The IMMULITE® Folic Acid Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Folic Acid assay on the IMMULITE 2000 systems.

The IMMULITE® Vitanin B12 Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Vitamin B12 assay on the IMMULITE 2000 systems.

Device Description

The IMMULITE® 2000 Cortisol Calibration Verification Material (CVM) contains one set of four vials each 3mL. CVM1 contains human serum with preservatives and CVM2, CVM3, and CVM4 contain various levels of cortisol in human serum with preservatives.

The IMMULITE® 2000 Folic Acid Calibration Verification Material (CVM) contains one set of four vials, 3mL (CVM1) each. when reconstituted. CVM1 contains a lyophilized human albumin based matrix with preservatives. CVM2. CVM3. and CVM4 contain various levels of lyophilized folic acid in human albumin based matrix with preservatives.

IMMULITE® 2000 Vitamin B12 Calibration Verification Material (CVM) contains one set of four vials, 3 mL each, when reconstituted. CVM1 contains a lyophilized human albumin-based matrix with preservatives. CVM2, CVM3, and CVM4 contain various levels of lyophilized Vitamin B12 in human albumin-based matrix with preservatives.

AI/ML Overview

The provided text describes three distinct devices: IMMULITE® 2000 Cortisol Calibration Verification Material, IMMULITE® 2000 Folic Acid Calibration Verification Material, and IMMULITE® 2000 Vitamin B12 Calibration Verification Material. Each device has its own acceptance criteria and associated study details.

Here's an analysis for each device as requested:


Device 1: IMMULITE® 2000 Cortisol Calibration Verification Material

1. Table of Acceptance Criteria and Reported Device Performance

CVM LevelAcceptance Criteria (Part 1 - Dose Value Range)Reported Device Performance (Target Mean and Guideline ±2SD Range)
LCOCVM1N/A (Guideline acceptance criteria not specified for CVM1)Target Mean: 0.00 g/dL, Guideline Range: 0 - 1.0 g/dL
LCOCVM2±20% of assigned doseTarget Mean: 4.54 g/dL, Guideline Range: 3.64 - 5.45 g/dL
LCOCVM3±15% of assigned doseTarget Mean: 18.7 g/dL, Guideline Range: 15.9 - 21.5 g/dL
LCOCVM4±19% of assigned doseTarget Mean: 54.5 g/dL, Guideline Range: 44.1 - 64.9 g/dL
Additional Acceptance Criteria (Part 2)Dose value of controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. (Used if Part 1 criteria not met).Not explicitly reported as a separate test, but implied to be met since stability study concluded product maintains optimal performance.
Shelf Life StabilityStable up to 14 months when stored at -20°C prior to opening.Confirmed by real-time shelf life study.
Open Component (In-use) StabilityStable for 8 hours at ambient or room temperature (15-25°C) after opening.Confirmed by testing at 2-hourly intervals for up to 9 hours.

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

  • Sample Size (Test Set):
    • Stability Studies: CVM levels (LCOCVM1, LCOCVM2, LCOCVM3, LCOCVM4) run in duplicate (as a minimum) at specified time points (1, 182, 365, 425 days).
    • Open Component Testing: Lot 090 CVMs were tested at 2-hourly intervals for up to 9 hours.
    • Value Assignment Validation: Six levels of commercially available controls, 25 patient serum samples, 3 spiked normal serum samples, and 5 normal serum samples were used to validate calibrator/CVM value assignments.
    • Expected Values/Target Values/Reference Range Establishment: Each CVM level was tested for a total of 27 replicates (9 runs, 3 replicates per run) using 3 different reagent kit lots and 8 IMMULITE 2000 systems.
  • Data Provenance: Not explicitly stated (e.g., country of origin). Appears to be based on internal laboratory studies ("Calibrators are not commercialized but are used internally during manufacture and release testing"). The studies are prospective in nature for stability testing.

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

  • Not applicable in the context of this device. Ground truth is established through internal gravimetric preparation and reference calibrator curves, with values determined by multiple runs on multiple instruments. There's no mention of human expert interpretation for device performance evaluation.

4. Adjudication Method

  • Not applicable. The performance is assessed against predefined numerical acceptance criteria and statistical ranges, not through an adjudication process involving human experts.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

  • Not applicable. This is a calibration verification material, not a device for human interpretation or diagnosis.

6. Standalone Performance

  • Yes, the performance testing described is for the device (IMMULITE® 2000 Cortisol CVM) in a standalone context, as it evaluates the material's stability and value assignment on the IMMULITE 2000 system. It's not an AI algorithm, but the "standalone performance" concept applies in that the material's performance is assessed intrinsically.

7. Type of Ground Truth Used

  • Stability and Value Assignment: Traceable to an internal material which has been gravimetrically prepared. CVMs are manufactured using qualified materials and measurement procedures. Dose values are generated from a reference calibrator curve created by assigned reference calibrators, with values averaged across all systems.
  • Expected Values/Target Ranges: Established based on the Target Mean and ± 2 Standard Deviation (SD) from extensive testing (27 replicates, 9 runs, 3 replicates/run, 3 kit lots, 8 IMMULITE 2000 systems).

8. Sample Size for the Training Set

  • The term "training set" is not directly applicable to a calibration verification material. However, the data used to establish the reference calibrator curve (from which CVM dose values are generated) and the target values are analogous to a training dataset in that they define the expected performance.
  • For the reference calibrator curve: Not specified in detail, but it's part of the internal manufacturing and release testing of Cortisol reagents and two-point adjustors.
  • For CVM Target Values: Each CVM level was tested for a total of 27 replicates (9 runs, 3 replicates per run) using 3 different reagent kit lots and 8 IMMULITE 2000 systems to establish the target mean and SD.

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

  • Reference Calibrator Curve: The CVMs are "value assigned using assigned reference calibrators." These calibrators are internally used during manufacture and release testing. The CVMs' dose values are generated using the curve established by these assigned reference calibrators. The underlying ground truth for these reference calibrators is based on gravimetric preparation and qualified measurement procedures.
  • CVM Target Values: Established through extensive testing on multiple systems and reagent lots, calculating the mean and standard deviation from these empirical measurements, and then applying a 95% confidence interval ($\pm 2SD$).

Device 2: IMMULITE® 2000 Folic Acid Calibration Verification Material

1. Table of Acceptance Criteria and Reported Device Performance

CVM LevelAcceptance Criteria (Part 1 - Dose Value Range)Reported Device Performance (Target Mean and Guideline ±2SD Range)
LFOCVM1N/A (Guideline acceptance criteria not specified for CVM1)Target Mean: 0.00 ng/mL, Guideline Range: 0.00 - 1.0 ng/mL
LFOCVM2±15% of assigned doseTarget Mean: 3.11 ng/mL, Guideline Range: 2.55 - 3.67 ng/mL
LFOCVM3±10% of assigned doseTarget Mean: 12.4 ng/mL, Guideline Range: 10.9 - 13.9 ng/mL
LFOCVM4±12% of assigned doseTarget Mean: 26.3 ng/mL, Guideline Range: 23.1 - 29.5 ng/mL
Additional Acceptance Criteria (Part 2)Dose value of controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. (Used if Part 1 criteria not met).Not explicitly reported as a separate test, but implied to be met since stability study concluded product maintains optimal performance.
Shelf Life StabilityStable up to 3.5 years when stored at -20°C prior to opening.Confirmed by real-time shelf life study.
Open Component (In-use) StabilityStable for 8 hours at ambient or room temperature (15-25°C) after reconstitution.Confirmed by testing at 2-hourly intervals for up to 9 hours.

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

  • Sample Size (Test Set):
    • Stability Studies: CVM levels (LFOCVM1, LFOCVM2, LFOCVM3, LFOCVM4) run in duplicate (as a minimum) at specified time points (1, 912, 1095, 1280 days).
    • Open Component Testing: Lot 090B Folic Acid CVMs were tested at 2-hourly intervals for up to 9 hours.
    • Value Assignment Validation: Six levels of commercially available controls and 14 patient serum samples were used to validate calibrator/CVM value assignments.
    • Expected Values/Target Values/Reference Range Establishment: Folic Acid CVMs were tested on 27 replicates in total (9 runs, 3 replicates per run) on 6 IMMULITE 2000 systems and 3 different reagent kit lots.
  • Data Provenance: Not explicitly stated (e.g., country of origin). Appears to be based on internal laboratory studies (calibrators used internally). The studies are prospective in nature for stability testing.

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

  • Not applicable as this is a calibration verification material. Ground truth is established through internal gravimetric preparation, reference calibrator curves, and empirical measurements on multiple instruments. No human expert interpretation is involved in performance evaluation.

4. Adjudication Method

  • Not applicable. Performance is assessed against numerical acceptance criteria and statistical ranges.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

  • Not applicable. This is a calibration verification material.

6. Standalone Performance

  • Yes, performance testing is for the device in a standalone context, evaluating its stability and value assignment on the IMMULITE 2000 system.

7. Type of Ground Truth Used

  • Stability and Value Assignment: Traceable to an internal material which has been gravimetrically prepared. CVMs are manufactured using qualified materials and measurement procedures. Dose values are generated from a reference calibrator curve created by assigned reference calibrators, with values averaged across all systems.
  • Expected Values/Target Ranges: Established based on the Target Mean and ± 2 Standard Deviation (SD) from extensive testing (27 replicates, 9 runs, 3 replicates/run, 6 IMMULITE 2000 systems, 3 kit lots).

8. Sample Size for the Training Set

  • Similar to the Cortisol CVM, the "training set" concept is not directly applicable.
  • For the reference calibrator curve: Not specified in detail, but part of internal manufacturing and release testing of Folic Acid reagents and two-point adjustors.
  • For CVM Target Values: The Folic Acid CVMs were tested on 27 replicates (9 runs, 3 replicates per run) on 6 IMMULITE 2000 systems and 3 different reagent kit lots to establish the target mean and SD.

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

  • Reference Calibrator Curve: The CVMs are "value assigned using assigned reference calibrators." These calibrators are internally used during manufacture and release testing. The CVMs' dose values are generated using the curve established by these assigned reference calibrators. The underlying ground truth for these reference calibrators is based on gravimetric preparation and qualified measurement procedures.
  • CVM Target Values: Established through extensive empirical testing (27 replicates on multiple systems and reagent lots) to calculate the mean and standard deviation, followed by defining a 95% confidence interval ($\pm 2SD$).

Device 3: IMMULITE® 2000 Vitamin B12 Calibration Verification Material

1. Table of Acceptance Criteria and Reported Device Performance

CVM LevelAcceptance Criteria (Part 1 - Dose Value Range)Reported Device Performance (Target Mean and Guideline ±2SD Range)
LVBCVM1N/A (Guideline acceptance criteria not specified for CVM1)Target Mean: 0.00 pg/mL, Guideline Range: 0.00 - 150 pg/mL
LVBCVM2±10% of assigned doseTarget Mean: 234 pg/mL, Guideline Range: 187 - 281 pg/mL
LVBCVM3±10% of assigned doseTarget Mean: 579 pg/mL, Guideline Range: 510 - 648 pg/mL
LVBCVM4±21% of assigned doseTarget Mean: 1144 pg/mL, Guideline Range: 755 - 1533 pg/mL
Additional Acceptance Criteria (Part 2)Dose value of controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. (Used if Part 1 criteria not met).Not explicitly reported as a separate test, but implied to be met since stability study concluded product maintains optimal performance.
Shelf Life StabilityStable up to 69 months when stored at -20°C prior to opening.Confirmed by real-time shelf life study.
Open Component (In-use) StabilityStable for 8 hours at room (ambient) temperature (15-25°C) after reconstitution.Confirmed by testing at 2-hourly intervals for up to 9 hours.

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

  • Sample Size (Test Set):
    • Stability Studies: CVM levels (LVBCVM1, LVBCVM2, LVBCVM3, LVBCVM4) run in duplicate (at the minimum) at specified time points (0, 67, 68, 69 months).
    • Open Component Testing: Lot 108 Vitamin B12 CVMs were tested at 2-hourly intervals for up to 9 hours.
    • Value Assignment Validation: Eight levels of commercially available controls and 21 patient serum samples were used to validate CVM value assignments.
    • Expected Values/Target Values/Reference Range Establishment: Vitamin B12 CVMs were tested on 24 replicates in total (12 runs, 2 replicates per run) using 3 IMMULITE 2000 and 5 IMMULITE/IMMULITE 1000 systems, and 4 different reagent kit lots.
  • Data Provenance: Not explicitly stated (e.g., country of origin). Appears to be based on internal laboratory studies (calibrators used internally). The studies are prospective in nature for stability testing.

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

  • Not applicable as this is a calibration verification material. Ground truth is established through internal gravimetric preparation, internal reference standards, reference calibrator curves, and empirical measurements on multiple instruments. No human expert interpretation is involved in performance evaluation.

4. Adjudication Method

  • Not applicable. Performance is assessed against numerical acceptance criteria and statistical ranges.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

  • Not applicable. This is a calibration verification material.

6. Standalone Performance

  • Yes, performance testing is for the device in a standalone context, evaluating its stability and value assignment on the IMMULITE 2000 and IMMULITE/IMMULITE 1000 systems.

7. Type of Ground Truth Used

  • Stability and Value Assignment: Traceable to an internal standard. CVMs are manufactured using qualified materials and measurement procedures. Dose values are generated from a reference calibrator curve created by assigned reference calibrators, with values averaged across all systems.
  • Expected Values/Target Ranges: Established based on the Target Mean and ± 2 Standard Deviation (SD) from extensive testing (24 replicates, 12 runs, 2 replicates/run, 8 IMMULITE systems, 4 kit lots).

8. Sample Size for the Training Set

  • The "training set" concept is not directly applicable.
  • For the reference calibrator curve: Not specified in detail, but part of internal manufacturing and release testing of Vitamin B12 reagents and two-point adjustors.
  • For CVM Target Values: The Vitamin B12 CVMs were tested on 24 replicates (12 runs, 2 replicates per run) using 3 IMMULITE 2000 and 5 IMMULITE/IMMULITE 1000 systems, and 4 different reagent kit lots to establish the target mean and SD.

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

  • Reference Calibrator Curve: The CVMs are "value assigned reference calibrators." These calibrators are internally used during manufacture and release testing. The CVMs' dose values are generated using the curve established by these assigned reference calibrators. The underlying ground truth for these reference calibrators is based on internal standards and qualified measurement procedures.
  • CVM Target Values: Established through extensive empirical testing (24 replicates on multiple systems and reagent lots) to calculate the mean and standard deviation, followed by defining a 95% confidence interval ($\pm 2SD$).

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1

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: ______k1414444

1. SubmitterMailing Address:Siemens Healthcare Diagnostics Inc.5210 Pacific Concourse DriveLos Angeles, CA 90045
Contact Person:Phone Number:Fax Number:E-mail Address:Date Prepared:Donna VelasquezRegulatory Technical Specialist(310)-645-8200 x7403(310)-645-9999donna.velasquez@siemens.comMay 30, 2014
2. Device NameProprietary Name:Measurand:Type of Test:Regulation Section:Classification:Products Code:Panel:IMMULITE® 2000 Cortisol Calibration Verification MaterialQuality Control materials for IMMULITE® 2000 Cortisol assayCalibration Verification Material (CVM) for IMMULITE® 2000Cortisol assay21 CFR 862.1660, Quality Control MaterialClass I ReservedJJX - Single (Specified) Analyte Controls (Assayed andUnassayed)Clinical Chemistry (75)
3. Predicate Device NamePredicate 510(k) No:IMMULITE® 2000 Total T3 Calibration Verification Material(CVM)K133124
4. Device Description:The IMMULITE® 2000 Cortisol Calibration Verification Material(CVM) contains one set of four vials each 3mL. CVM1 containshuman serum with preservatives and CVM2, CVM3, and CVM4contain various levels of cortisol in human serumwithpreservatives.
5. Intended Use:Indication for Use:See Indications for Use Statement belowThe IMMULITE® Cortisol Calibration Verification Material(CVM) is for in vitro diagnostic use in the verification ofcalibration of the IMMULITE Cortisol assay on the IMMULITE2000 systems
Special Conditions forUse Statement(s):Special InstrumentRequirements:For prescription use onlyIMMULITE® 2000 Systems

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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 Cortisol Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.

SIMILARITIES
Candidate DeviceIMMULITE 2000 Cortisol CVMPredicate DeviceIMMULITE 2000 Total T3 CVM
IntendedUseThe IMMULITE® Cortisol CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration of the IMMULITE Cortisolassay on the IMMULITE 2000 systems.The IMMULITE® Total T3Calibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Total T3 assay on theIMMULITE 2000 systems
Storage-20°CSame
FormLiquidSame
StabilityStable unopened until theexpiration dateSame
Levels4Same
MatrixHuman Serum with preservativesSame
UseSingle Use OnlySame
DIFFERENCES
Candidate DeviceIMMULITE 2000 Cortisol CVMPredicate DeviceIMMULITE 2000 Total T4 CVM
AnalyteCortisolTotal T3

Table 1: Substantial Equivalence Comparison

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 real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 Cortisol Calibration Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Verification Materials are stable up to 14 months when stored at -20°C prior to opening and stable for 8 hours at ambient or room temperature (15-25°C) after opening.

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Stability Protocol Summary:

The CVM study protocols are run as part of the calibrator stability testing. The stability calibrators/CVMs are run in duplicate (as a minimum) at the time points shown in Table 2, and the dose value is determined from the reference calibrator curve.

CVM LevelTime-Points(Days)
LCOCVM11182365425
LCOCVM21182365425
LCOCVM31182365425
LCOCVM41182365425

Table 2: Stability Protocol Summary

For Open Component testing, the results were determined from a 2-point adjustment. Using IMMULITE 2000 Cortisol (L2KCO) kit lot 362, lot 090 CVMs were tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the Cortisol Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability

calibrators/CVM to fall between ±20% of assigned dose for CVM level 2, ±15% of assigned dose for level 3 and ±19% of assigned dose for level 4. Part 2 review limits criteria which require dose value of the controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±20% for level 2, ±15% of assigned dose for level 3 and within ±19% of assigned dose for level 4, then additional data review is conducted using part 2 criteria.

Traceability:

The IMMULITE Cortisol CVMs are traceable to an internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE Cortisol CVMs are 4 level materials which are a subset of 8 level Cortisol calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Cortisol reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. 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. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. Six levels of commercially available controls and 25 patient serum samples, 3 spiked normal serum samples and 5 normal serum samples were used to validate calibrator/CVM value assignments.

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Expected Values/Target Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run, 3 different reagent kit lots and 8 IMMULITE 2000 systems. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The target values are provided in the IMMULITE® 2000 CVM Calibration Material lotspecific value card. The expected assay range is 1 to 50 g/dL. The target values in Table 3 can be considered as guidelines.

Analyte targetlevelsCVM Level*TargetMeang/dL)StandardDeviation(SD)Guideline ±2SDRange
LCOCVM10.00-0.1.0
LCOCVM24.540.4553.5.45
LCOCVM318.71.41521.5
LCOCVM454.55.24464.9
Assay Range1 to 50 g/dL

Table 3: Analyte Target Range Values

*Note: when CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software. If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.

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

8. Conclusion:

The IMMULITE® 2000 Cortisol Calibration Verification Material is substantially equivalent to the predicate device intended for similar use. 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, the IMMULITE® 2000 Cortisol 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: K141444

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

Siemens Healthcare Diagnostics Inc. 5210 Pacific Concourse Drive Los Angeles. CA 90045

Donna Velasquez Regulatory Technical Specialist (310) 645-8200 x7403 (310) 645-9999 donna.velasquez@siemens.com May 30, 2014

IMMULITE® 2000 Folic Acid Calibration Verification Material Quality Control materials for IMMULITE® 2000 Folic Acid assay Calibration Verification Material (CVM) for IMMULITE® 2000 Folic Acid assay 21 CFR 862.1660, Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassaved) Clinical Chemistry (75)

IMMULITE 2000 DHEA-SO4 Calibration Verification Material (CVM) K140258

The IMMULITE® 2000 Folic Acid Calibration Verification Material (CVM) contains one set of four vials, 3mL (CVM1) each. when reconstituted. CVM1 contains a lyophilized human albumin based matrix with preservatives. CVM2. CVM3. and CVM4 contain various levels of lyophilized folic acid in human albumin based matrix with preservatives.

See Indications for Use Statement below The IMMULITE® Folic Acid Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Folic Acid assay on the IMMULITE 2000 systems

For prescription use only

IMMULITE® 2000 Systems

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    1. Technological Characteristics and Substantial Equivalence Comparison with Predicate:
      A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Folic Acid Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.
SIMILARITIES
Candidate DeviceIMMULITE 2000 Folic Acid CVMPredicate DeviceIMMULITE 2000 DHEA-SO4CVM
IntendedUseThe IMMULITE® Folic AcidCalibration Verification Material (CVM)is for in vitro diagnostic use in theverification of calibration of theIMMULITE Folic Acid assay on theIMMULITE 2000 systemsThe IMMULITE® DHEA-SO4Calibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration ofthe IMMULITE DHEA-SO4 assayon the IMMULITE 2000 systems
FormLyophilizedSame
Levels4Same
StabilityStable unopened until the expiration dateSame
Storage-20°CSame
UseSingle Use OnlySame
Table 1: Substantial Equivalence Comparison
-----------------------------------------------------
DIFFERENCES
Candidate DeviceIMMULITE 2000 Folic Acid CVMPredicate DeviceIMMULITE 2000 DHEA-SO4CVM
AnalyteFolic AcidDHEA-SO4
MatrixHuman Albumin with preservativesHuman Serum with Preservatives

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 real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 Folic Acid 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 Calibration Verification Materials are stable up to 3.5 years when stored at -20°C prior to opening, and for 8 hours at ambient or room temperature (15-25°C) after reconstitution.

Stability Protocol Summary:

1

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) at the time points shown in Table 2 and the dose value determined from the reference calibrator curve.

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CVM LevelTime-Points(Days)
LFOCVM1191210951280
LFOCVM2-191210951280
LFOCVM3191210951280
LFOCVM4191210951280

Table 2: Stability Protocol Summary

For Open Component testing, the results were determined from a 2-point adjustment. Using IMMULITE 2000 Folic Acid (L2KFO) kit lot 446, lot 090B Folic Acid CVMs were tested at 2hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Folic Acid Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability CVMs to fall between ±15% of the assigned dose for CVM level 2, within ±10% of the assigned dose for level 3 and within ±12% of assigned dose for CVM level 4. Part 2 review limits criteria which require dose value of the controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±15% of the assigned dose for CVM level 2, within ±10% of the assigned dose for level 3 and within ±12% of assigned dose for CVM level 4 then additional data review is conducted using part 2 criteria.

Traceability:

The IMMULITE Folic Acid CVMs are traceable to an internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE Folic Acid CVMs are 4 level materials which are a subset of 8 level Folic Acid calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Folic Acid reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. 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. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The controls must fall within their target ranges. Six levels of commercially available controls and 14 patient serum samples were used to validate calibrator/CVM value assignments.

Expected Values/Target Values/Reference Range:

The CVMs are manufactured using qualified materials and measurement procedures. The Folic Acid CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run on 6 IMMULITE 2000 systems and 3 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. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected assay range is 1 to 24 ng/mL. The target values in Table 3 can be considered as guidelines.

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Table 3: Analyte Target Range Levels

Analyte targetlevelsCVM Level*TargetMean(ng/mL)StandardDeviation(SD)Guideline ±2SD Range(ng/mL)
LFOCVM10.00-0.001.0
LFOCVM23.110.282.553.67
LFOCVM312.40.7510.913.9
LFOCVM426.31.623.129.5
Assay Range1 to 24 ng/mL

*Note: when CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software. If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.

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

8. Conclusion:

The IMMULITE® 2000 Folic Acid Calibration Verification Material is substantially equivalent to the predicate device intended for similar use. 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, the IMMULITE® 2000 Folic Acid 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: K141444

the assigned 510(k) Number:K141444
1. SubmitterMailing Address:Siemens Healthcare Diagnostics Inc.5210 Pacific Concourse DriveLos Angeles, CA 90045
Contact Person:Phone Number:Fax Number:E-mail Address:Date Prepared:Donna VelasquezRegulatory Technical Specialist(310)-645-8200 x7403(310)-645-9999donna.velasquez@siemens.comMay 30, 2014
2. Device NameProprietary Name:Measurand:Type of Test:Regulation Section:Classification:Products Code:Panel:IMMULITE® 2000 Vitamin B12 Calibration Verification MaterialQuality Control materials for IMMULITE 2000 Vitamin B12Calibration Verification Material (CVM) for IMMULITE® 2000Vitamin B12 assay21 CFR 862.1660, Quality Control MaterialClass I ReservedJJX - Single (Specified) Analyte Controls (Assayed and Unassayed)Clinical Chemistry (75)
3. Predicate Device NamePredicate 510(k) No:IMMULITE® 2000 DHEA-SO4 Calibration Verification MaterialK140258
4. Device Description:IMMULITE® 2000 Vitamin B12 Calibration Verification Material(CVM) contains one set of four vials, 3 mL each, when reconstituted.CVM1 contains a lyophilized human albumin-based matrix withpreservatives. CVM2, CVM3, and CVM4 contain various levels oflyophilized Vitamin B12 in human albumin-based matrix withpreservatives.
5. Intended Use:Indication for Use:See Indications for Use Statement belowThe IMMULITE® Vitamin B12 Calibration Verification Material(CVM) is for in vitro diagnostic use in the verification of theIMMULITE Vitamin B12 assay on the IMMULITE 2000 systems
Special Conditions forUse Statement(s):Special InstrumentRequirements:For prescription use onlyIMMULITE® 2000 Systems

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    1. Technological Characteristics A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Vitamin B12 and Substantial Equivalence Calibration Verification Material (CVM) is substantially equivalent Comparison with Predicate: to the predicate device, as summarized in Table 1.

Table 1: Substantial Equivalence Comparison

SIMILARITIES
Candidate DeviceIMMULITE 2000 Vitamin B12 CVMPredicate DeviceIMMULITE 2000 DHEA-SO4 CVM
IntendedUseThe IMMULITE® Vitamin B12Calibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Vitamin B12 assay on theIMMULITE 2000 systems.The IMMULITE® DHEA-SO4Calibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE DHEA-SO4 assay on theIMMULITE 2000 systems
FormLyophilizedSame
StabilityStable unopened until theexpiration dateSame
Storage-20°CSame
Levels4Same
UseSingle Use OnlySame
DIFFERENCES
Candidate DeviceIMMULITE 2000 Vitamin B12 CVMPredicate DeviceIMMULITE 2000 DHEA-SO4 CVM
AnalyteVitamin B12DHEA-SO4
MatrixHuman Albumin with preservativesHuman Serum with preservatives

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 real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 Vitamin B12 CVM to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Verification Materials are stable up to 69 months when stored at -20°C prior to opening and stable for 8 hours at room (ambient) temperature (15-25°C) after reconstitution.

Stability Protocol Summary:

The CVM study protocols are run as part of the calibrator stability testing. As summarized in Table 2, the testing was run in duplicate (at the minimum) and contains time-points at which the testing was performed.

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CVM LevelTime-Points(Months)
LVBCVM10676869
LVBCVM20676869
LVBCVM30676869
LVBCVM40676869

For Open Component testing, the results were determined from a 2-point adjustment. Using IMMULITE 2000 Vitamin B12 (L2KVB) kit lot 467, lot 108 Vitamin B12 CVMs were tested at 2hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Vitamin B12 Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability calibrator/CVM to fall between ±10% of assigned dose for CVM level 2 and level 3 and within ±21% of assigned dose for CVM level 4. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±10% for level 3 and ±21% for level 4, then additional data review is conducted using part 2 criteria.

Traceability:

The IMMULITE Vitamin B12 CVMs are traceable to an internal standard. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE® 2000 Vitamin B12 CVMs are 4 level materials which are a subset of 8 level Vitamin B12 calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Vitamin B12 reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned reference calibrators. 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 and controls using the assigned CVM values. Eight levels of commercially available controls and 21 patient serum samples were used to validate CVM value assignments.

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Expected Values/Target Values/Reference Range:

The Vitamin B12 CVMs were tested on 24 replicates in total comprised of 12 runs and 2 replicates per run, 3 IMMULITE 2000 and 5 IMMULITE/IMMULITE 1000 systems and 4 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 and controls using the assigned CVM values. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected assay range is 150 to 1000 pg/mL. The target values in Table 3 can be considered as guidelines.

Analyte targetlevelsLevel*Target Mean(ng/mL)StandardDeviation(SD)Guideline ±2SD Range(ng/mL)
LVBCVM10.00-0.00 - 150
LVBCVM223423.5187 - 281
LVBCVM357934.5510 - 648
LVBCVM41144194.5755 - 1533
Assay Range150 to 1000 pg/mL

Table 3: Analyte Target Range Levels

*Note: when CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software. If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.

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 Vitamin B12 Calibration Material is substantially equivalent to the predicate device intended for similar use. 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, the IMMULITE® 2000 Vitamin B12 Calibration Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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Image /page/12/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's emblem, which is a stylized caduceus, a symbol often associated with medicine and healthcare. The emblem is positioned to the right of the department's name, which is written in a circular arrangement around the emblem. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA".

Public Health Service

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

July 9, 2014

SIEMENS HEALTHCARE DIAGNOSTICS, INC. C/O DONNA VELASQUEZ REGULATORY TECHNICAL SPECIALIST 5210 PACIFIC CONCURSE DRIVE LOS ANGELES CA 90045

Re: K141444

Trade/Device Name: IMMULITE® 2000 Cortisol Calibration Verification Material IMMULITE® 2000 Folic Acid Calibration Verification Material IMMULITE® 2000 Vitamin B12 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: June 3, 2014 Received: June 5, 2014

Dear Donna Velasquez:

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 Part 801); medical device reporting (reporting of medical

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Page 2 - Ms. Donna Velasquez

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 clectronic 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 regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resources/orYou/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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

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

Sincerely yours,

Courtney H. Lias -S

Courtney H. Lias Director Division of Chemistry and Toxicology 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

Form Approved: OMB No. 0910-0120 Expiration Dale: January 31, 2017 See PRA Statement below.

510(k) Number (if known) K141444

Device Name

IMMULITE® 2000 Cortiso! Calibration Verification Material IMMULITE® 2000 Folic Acid Calibration Verification Material IMMULITE® 2000 Vitamin B12 Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® Corlisol Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Cortisol assay on the IMMULITE 2000 systems.

The IMMULITE® Folic Acid Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Folic Acid assay on the IMMULITE 2000 systems.

The IMMULITE® Vitanin B12 Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Vitamin B12 assay on the IMMULITE 2000 systems.

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

2 Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpant 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) (Signalure)

Yung W. Chan -S

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

*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.4

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

Department of Health and Human Services Food and Orug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStall@lda.hhs.gov

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

§ 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.