(30 days)
The IMMULITE 2000 DHEA-SO4 Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE DHEA-SO4 assay on the IMMULITE 2000 systems.
The IMMULITE 2000 Third Generation Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Third Generation TSH assay on the IMMULITE 2000 systems.
The IMMULITE 2000 Intact PTH Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Intact PTH assay on the IMMULITE 2000 systems.
The Calibration Verification Material (CVM) contains one set of four vials each 2.0mL after reconstitution. CVM1 contains human serum with preservatives. CVM2, CVM 3 and CVM4 contain various levels of lyophilized DHEA-SO4 in human serum with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 3 mL each after reconstitution. CVM 1 contains an equine serum/buffer matrix with preservatives. CVM2. CVM3 and CVM4 various levels of lyophilized TSH in an equine serum/buffer matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, with 4 mL for CVM1 and 2 mL each for CVM2, CVM3 and CVM4 after reconstitution. CVM1 contains a buffered bovine protein matrix with preservatives. CVM2, CVM3 and CVM4 contain various levels of lyophilized synthetic human intact PTH in buffered bovine protein matrix with preservatives.
Here's a breakdown of the acceptance criteria and study information for each of the three devices mentioned in the document: IMMULITE® 2000 DHEA-SO4 Calibration Verification Material, IMMULITE® 2000 Third Generation TSH Calibration Verification Material, and IMMULITE® 2000 Intact PTH Calibration Verification Material.
Device 1: IMMULITE® 2000 DHEA-SO4 Calibration Verification Material
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Guideline) | Acceptable Dose Range (µg/dL) | Reported Performance (Implied by meeting criteria) |
|---|---|---|---|
| LDSCVM1 | Not Applicable (Controls within 2SD of target) | Not Applicable | Met (controls within 2SD) |
| LDSCVM2 | Dose value between ±15% of assigned dose | 39.9 - 53.9 | Met (within 39.9 - 53.9 µg/dL) |
| LDSCVM3 | Dose value between ±10% of assigned dose | 437.4 - 534.6 | Met (within 437.4 - 534.6 µg/dL) |
| LDSCVM4 | Dose value between ±15% of assigned dose | 894.2 - 1209.8 | Met (within 894.2 - 1209.8 µg/dL) |
Note: The document states that the device "meets the performance specifications for its intended use" and "supports the claims of substantial equivalence," implying that these stability acceptance criteria were met.
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: Each CVM level was tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, on 9 systems and 4 different reagent kit lots.
- Data Provenance: Not explicitly stated, but assumed to be internal laboratory data generated by Siemens Healthcare Diagnostics Inc. This is a prospective study for stability testing.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not applicable. The ground truth (assigned dose values) for the CVMs are established through internal reference calibrators prepared gravimetrically and validated using quality control and patient samples. No human expert 'ground truth' is explicitly mentioned for the test set evaluation.
4. Adjudication method for the test set
- Two-part criteria:
- Part 1 (Guideline Criteria): Dose value of stability calibrators/CVM must fall within specified percentage differences of the assigned dose (e.g., ±15% for CVM level 2).
- Part 2 (Review Limits Criteria): If Part 1 is not met, a secondary review is conducted, requiring the dose value of controls to be within 2 standard deviations (SD) of the control target value when generated from the stability calibrator curve.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- Not applicable. This is a performance study for an in vitro diagnostic calibration verification material, not an AI-assisted diagnostic device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not applicable. This is a performance study for an in vitro diagnostic calibration verification material.
7. The type of ground truth used
- Assigned Dose Values: Ground truth for the CVMs (assigned dose values) is established through internal reference calibrators prepared gravimetrically. This is a form of traceable reference standard. Validation also includes testing with commercially available controls and normal human serum samples.
8. The sample size for the training set
- Not applicable in the context of a "training set" for an algorithm. However, for "value assignment" (which establishes the initial reference values these CVMs verify), six levels of commercially available controls and 30 normal serum samples were used.
9. How the ground truth for the training set was established
- Not applicable as a "training set". For value assignment (establishment of reference values), the IMMULITE DHEA-SO4 CVMs are traceable to an internal material that has been gravimetrically prepared. The CVMs are a subset of 7-level DHEA-SO4 calibrators. These calibrators are value assigned using assigned reference calibrators prepared using DHEA-SO4 antigen stock traceable to gravimetrically prepared internal material.
Device 2: IMMULITE® 2000 Third Generation TSH Calibration Verification Material
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Guideline) | Acceptable Dose Range (µIU/mL) | Reported Performance (Implied by meeting criteria) |
|---|---|---|---|
| LTSCVM1 | Not Applicable (Controls within 2SD of target) | Not Applicable | Met (controls within 2SD) |
| LTSCVM2 | Dose value between ±10% of assigned dose | 0.52 - 0.64 | Met (within 0.52 - 0.64 µIU/mL) |
| LTSCVM3 | Dose value between ±12% of assigned dose | 3.81 - 4.85 | Met (within 3.81 - 4.85 µIU/mL) |
| LTSCVM4 | Dose value between ±16% of assigned dose | 63.00 - 87.00 | Met (within 63.00 - 87.00 µIU/mL) |
Note: The document states that the device "meets the performance specifications for its intended use" and "supports the claims of substantial equivalence," implying that these stability acceptance criteria were met.
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: Each CVM level was tested on 15 replicates in total, comprised of 5 runs, 3 replicates per run, on 5 systems and 5 different reagent kit lots.
- Data Provenance: Not explicitly stated, but assumed to be internal laboratory data generated by Siemens Healthcare Diagnostics Inc. This is a prospective study for stability testing.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not applicable. The ground truth (assigned dose values) for the CVMs are established through internal reference calibrators prepared using human TSH antigen spiked in an equine serum matrix and validated using quality control and patient samples. No human expert 'ground truth' is explicitly mentioned for the test set evaluation.
4. Adjudication method for the test set
- Two-part criteria:
- Part 1 (Guideline Criteria): Dose value of stability calibrators/CVM must fall within specified percentage differences of the assigned dose (e.g., ±10% for CVM level 2).
- Part 2 (Review Limits Criteria): If Part 1 is not met, a secondary review is conducted, requiring the dose value of controls to be within 2 standard deviations (SD) of the control target value when generated from the stability calibrator curve.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- Not applicable. This is a performance study for an in vitro diagnostic calibration verification material, not an AI-assisted diagnostic device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not applicable. This is a performance study for an in vitro diagnostic calibration verification material.
7. The type of ground truth used
- Assigned Dose Values (Traceable Reference Standard): Ground truth for the CVMs is traceable to WHO 2nd IRP 80/558. Additionally, the assigned reference calibrators are prepared using human TSH antigen spiked in equine serum matrix. Validation also includes testing with commercially available controls and spiked/normal patient samples.
8. The sample size for the training set
- Not applicable in the context of a "training set" for an algorithm. However, for "value assignment," seven levels of commercially available controls and 30 samples (10 spiked patient, 15 spiked normal, and 5 normal samples) were used to validate calibrator/CVM value assignments.
9. How the ground truth for the training set was established
- Not applicable as a "training set". For value assignment (establishment of reference values), the IMMULITE Third Generation TSH CVMs are traceable to WHO 2nd IRP 80/558. Calibrators (of which CVMs are a subset) are value assigned using assigned reference calibrators prepared using human TSH antigen spiked in an Equine Serum matrix with preservatives.
Device 3: IMMULITE® 2000 Intact PTH Calibration Verification Material
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Guideline) | Acceptable Dose Range (pg/mL) | Reported Performance (Implied by meeting criteria) |
|---|---|---|---|
| LPPCVM1 | Not Applicable (Controls within 2SD of target) | Not Applicable | Met (controls within 2SD) |
| LPPCVM2 | Dose value between ±12% of assigned dose | 13.4 - 17.0 | Met (within 13.4 - 17.0 pg/mL) |
| LPPCVM3 | Dose value between ±8% of assigned dose | 141.7 - 166.3 | Met (within 141.7 - 166.3 pg/mL) |
| LPPCVM4 | Dose value between ±12% of assigned dose | 3329.9 - 4238.1 | Met (within 3329.9 - 4238.1 pg/mL) |
Note: The document states that the device "meets the performance specifications for its intended use" and "supports the claims of substantial equivalence," implying that these stability acceptance criteria were met.
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: Each CVM level was tested on 27 replicates in total, comprised of 9 runs, 7 systems and 3 different reagent kit lots.
- Data Provenance: Not explicitly stated, but assumed to be internal laboratory data generated by Siemens Healthcare Diagnostics Inc. This is a prospective study for stability testing.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not applicable. The ground truth (assigned dose values) for the CVMs are established through internal reference calibrators prepared using synthetic human intact PTH and validated using quality control and patient samples. No human expert 'ground truth' is explicitly mentioned for the test set evaluation.
4. Adjudication method for the test set
- Two-part criteria:
- Part 1 (Guideline Criteria): Dose value of stability calibrator/CVM must fall within specified percentage differences of the assigned dose (e.g., ±12% for CVM level 2).
- Part 2 (Review Limits Criteria): If Part 1 is not met, a secondary review is conducted, requiring the dose value of controls to be within 2 standard deviations (SD) of the control target value when generated from the stability calibrator curve.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- Not applicable. This is a performance study for an in vitro diagnostic calibration verification material, not an AI-assisted diagnostic device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not applicable. This is a performance study for an in vitro diagnostic calibration verification material.
7. The type of ground truth used
- Assigned Dose Values (Traceable Reference Standard): Ground truth for the CVMs is traceable to an internal material that has been gravimetrically prepared. Assigned reference calibrators are prepared using synthetic Human Intact PTH (1-84) spiked in buffered bovine protein matrix. Validation also includes testing with commercially available controls and various patient samples (EDTA plasma, serum, EDTA dialysis, serum dialysis).
8. The sample size for the training set
- Not applicable in the context of a "training set" for an algorithm. However, for "value assignment," two levels of commercially available controls and 88 samples (32 EDTA plasma, 32 serum, 12 EDTA dialysis samples, and 12 serum dialysis samples) were used to validate calibrator/CVM value assignments.
9. How the ground truth for the training set was established
- Not applicable as a "training set". For value assignment (establishment of reference values), the IMMULITE Intact PTH CVMs are traceable to an internal material that has been gravimetrically prepared. Calibrators (of which CVMs are a subset) are value assigned using assigned reference calibrators prepared using synthetic Human Intact PTH (1-84) spiked in the buffered bovine protein matrix.
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MAR - 5 2014
Section 006: 510(k) Summary
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
长140258 The assigned 510(k) Number: _
| 1.SubmitterMailing Address: | Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591 | |||
|---|---|---|---|---|
| Contact Person:Phone Number:Fax Number:E-mail Address:Date Prepared: | Asha GartlandTechnical Regulatory Affairs Specialist(914)-524-3257(914)-524-2101asha.gartland@siemens.comJanuary 31, 2014 | |||
| 2. Device NameProprietary Name:Measurand:Type of Test: | IMMULITE® 2000 DHEA-SO4 Calibration Verification MaterialQuality Control materials for IMMULITE® 2000 DHEA-SO4 assayCalibration Verification Material (CVM) for IMMULITE® 2000DHEA-SO4 assay | |||
| Regulation Section:Classification :Products Code:Panel: | 21 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 Insulin Calibration Verification Material (CVM)K133128 | |||
| 4. Device Description: | The Calibration Verification Material (CVM) contains one set of fourvials each 2.0mL after reconstitution. CVM1 contains human serumwith preservatives. CVM2, CVM 3 and CVM4 contain various levelsof lyophilized DHEA-SO4 in human serum with preservatives. | |||
| 5. Intended Use:Indication for Use: | See Indications for Use Statement below:The IMMULITE® DHEA-SO4 Calibration Verification Material(CVM) is for in vitro diagnostic use in the verification of calibrationof the IMMULITE DHEA-SO4 assay on the IMMULITE 2000systems. |
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Special Conditions for Use Statement(s): Special Instrument Requirements:
-
- Technological Characteristics and Substantial Equivalence Comparison with Predicate:
For prescription use only
- Technological Characteristics and Substantial Equivalence Comparison with Predicate:
IMMULITE® 2000 Systems
A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 DHEA-SO4 Calibration Verification Material (CVM) is substantially cquivalent to the predicate device as summarized in Table 1.
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Table 1: Substantial Equivalence Comparison
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 DHEA-SO4 CVM | Predicate DeviceIMMULITE 2000 Insulin CVM | |
| IntendedUse | The IMMULITE® DHEA-SO4Calibration Verification Material (CVM) isfor in vitro diagnostic use in theverification of calibration of theIMMULITE DHEA-SO4 assay on theIMMULITE 2000 systems. | The IMMULITE® Insulin CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration of the IMMULITE Insulinassay on the IMMULITE 2000 systems. |
| Form | Lyophilized | Same |
| Levels | 4 | Same |
| Storage | ≤20°C | Same |
| Stability | Stable unopened until the expiration date | Same |
| Use | Single Use Only | Same |
.
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 DHEA-SO4 CVM | Predicate DeviceIMMULITE 2000 Insulin CVM | |
| Analyte | DHEA-SO4 | Insulin |
| Matrix | Human Serum with preservatives | Equine serum with preservatives |
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7. Non-Clinical Performance Testing
Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intended use. The following tests were performed on the candidate device.
7.1 Stability Summary:
The stability study was conducted to validate the real-time shelf life and In-Use (Open Component or open vial) claim for the IMMULITE 2000 DHEA-SO4 Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM before and after opening. The IMMULITE® 2000 DHEA-SO4 Calibration Verification Materials are stable up to 7 years when stored at -20°C prior to opening and stable for 8 hours at ambient or room temperature (15-25°C) after reconstitution.
7.1.1 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) at the time points shown in Table 2 and the dose value determined from the reference calibrator curve.
| CVM Level | Time-Points (Days) | ||||
|---|---|---|---|---|---|
| LDSCVM1 | 1 | 1642 | 1825 | 2555 | |
| LDSCVM2 | 1 | 1642 | 1825 | 2555 | |
| LDSCVM3 | 1 | 1642 | 1825 | 2555 | |
| LDSCVM4 | 1 | 1642 | 1825 | 2555 |
Table 2: Stability Time Points
For Open Component testing, the results are determined from a 2-point adjustment. Test CVMs were tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.
7.1.2 Stability Acceptance Criteria Summary:
The Acceptance Criteria for the DHEA-SO4 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 ±15% of assigned dose for CVM level 2, ±10% of assigned dose for level 3 and ±15% of assigned dose for 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 ±15% for CVM level 2, ±10% for level 3 and ±15% for level 4 then additional data review is conducted using part 2 criteria.
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The acceptance criterion is summarized in Table 3.
| CVM Level | Assigned Dose (µg/dL) | *Guideline Criteria % difference to assigned dose | Acceptable dose range (µg/dL) | **Review Limits |
|---|---|---|---|---|
| LDSCVM1 | 0.00 | Not Applicable | Not Applicable | Controls are within 2SD of target on each curve |
| LDSCVM2 | 46.9 | $\pm$ 15% | 39.9 - 53.9 | |
| LDSCVM3 | 486 | $\pm$ 10% | 437.4 - 534.6 | |
| LDSCVM4 | 1052 | $\pm$ 15% | 894.2 - 1209.8 |
Table 3 Acceptance criteria for stability of IMMULITE 2000 DHEA-SO4 CVM
7.2 Traceability:
The IMMULITE DHEA-SQ CVMs are traceable to an internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.
7.3 Value Assignment:
DHEA-SO4 CVMs are 4 level materials which are a subset of 7 level DHEA-SO4 calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of DHEA-SO4 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 DHEA-SO4 antigen stock and are traccable to an internal material which has been gravimetrically prepared. Six levels of commercially available controls and 30 normal serum samples were used to validate calibrator/CVM value assignments.
The CVMs are manufactured using qualified materials and measurement procedures. The DHEA-SO4 CVMs were tested on 27 replicates in total comprised of 9 runs, 3 replicates per run, on 9 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 cach 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 controls must fall within their target ranges.
7.4 Expected Values/Reference Range:
Each CVM level was tested on 27 replicates in total comprised of 9 runs, 3 replicates per run, on 9 systems and 4 different reagent kit lots. 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 package insert.
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The expected assay range is 1 - 1000 µg/dL. The target values in Table 4 can be considered as guidelines.
| Analytetarget levels | CVM Level | Target Mean(µg/dL) | StandardDeviation(SD) | Guideline ±2SD Range(µg/dL) |
|---|---|---|---|---|
| CVM1 | 0.00 | - | 0.00 $≤$ 15.00 | |
| CVM2 | 46.9 | 6.1 | 34.7 59.1 | |
| CVM3 | 486 | 43.5 | 399 573 | |
| CVM4 | 1052 | 84 | 884 1220 | |
| Assay Range | 1 - 1000 µg/dL |
Table 4: Target Values
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 DHEA-SO4 Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 Insulin Calibration Verification 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, the IMMULITE® 2000 DHEA-SO4 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: _______________________________________
| 1. Submitter | |
|---|---|
| Mailing Address: | Siemens Healthcare Diagnostics Inc. |
| 511 Benedict Avenue | |
| Tarrytown, NY 10591 | |
| Contact Person: | Asha Gartland |
| Technical Regulatory Affairs Specialist | |
| Phone Number: | (914)-524-3257 |
| Fax Number: | (914)-524-2101 |
| E-mail Address: | asha.gartland@siemens.com |
| Date Prepared: | January 31st, 2014 |
| 2. Device Name | |
| Proprietary Name: | IMMULITE® 2000 Third Generation TSH Calibration |
| Measurand: | Verification Material |
| Type of Test: | Quality Control materials for IMMULITE® 2000 Third GenerationTSH assay |
| Calibration Verification Material (CVM) for IMMULITE® 2000Third Generation TSH assay | |
| Regulation Section: | 21 CFR 862.1660, Quality Control Material |
| Classification: | Class I Reserved |
| Products Code: | JJX – Single (Specified) Analyte Controls (Assayed and Unassayed) |
| Panel: | Clinical Chemistry (75) |
| 3. Predicate Device Name | IMMULITE® 2000 Insulin Calibration Verification Material (CVM) |
| Predicate 510(k) No: | K133128 |
| 4. Device Description: | The Calibration Verification Material (CVM) contains one set of fourvials, 3 mL each after reconstitution. CVM 1 contains an equineserum/buffer matrix with preservatives. CVM2. CVM3 and CVM4various levels of lyophilized TSH in an equine serum/buffer matrixwith preservatives. |
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- Intended Use: Indication for Use: See Indications for Use Statement below The IMMULITE® Third Generation TSH Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Third Generation TSH assay on the IMMULITE 2000 systems
Special Conditions for Use Statement(s): Special Instrument Requirements:
For prescription use only
IMMULITE® 2000 Systems
- Technological Characteristics and Substantial Equivalence Comparison with Predicate:
A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Third Generation TSH Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.
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| Table 1: Substantial Equivalence Comparison | |
|---|---|
| --------------------------------------------- | -- |
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 Third GenerationTSH CVM | Predicate DeviceIMMULITE 2000 Insulin CVM | |
| Intended Use | The IMMULITE® Third GenerationTSH Calibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Third Generation TSHassay on the IMMULITE 2000 systems | The IMMULITE® InsulinCalibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration of theIMMULITE Insulin assay on theIMMULITE 2000 systems |
| Form | Lyophilized | Same |
| Matrix | Equine serum/buffer with preservatives | Same |
| Storage | ≤20°C | Same |
| Stability | Stable unopened until the expiration date | Same |
| Levels | 4 | Same |
| Use | Single Use Only | Same |
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 Third Generation TSHCVM | Predicate DeviceIMMULITE 2000 Insulin CVM | |
| Analyte | TSH | Insulin |
7. Non-Clinical Performance Testing
Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intended use. The following tests were performed on the candidate device.
7.1 Stability Summary:
The stability study was conducted to validate the real-time shelf life and In-Use (Open Component or open vial) claim for the IMMULITE 2000 Third Generation TSH Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM before and after The IMMULITE 2000 Third Generation TSH Calibration Verification Materials are opening. stable up to 1.5 years when stored frozen at -20°C prior to opening and stable for 8 hours at ambient or room temperature (15-25℃) after reconstitution.
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7.1.1 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) at the time points shown in Table 2 and the dose value determined from the reference calibrator curve.
Table 2: Stability Time Points
| CVM Level | Time-Points (Days) | |||
|---|---|---|---|---|
| LTSCVM1 | 1 | 182 | 365 | 548 |
| LTSCVM2 | 1 | 182 | 365 | 548 |
| LTSCVM3 | 1 | 182 | 365 | 548 |
| LTSCVM4 | 1 | 182 | 365 | 548 |
For Open Component testing, the results are determined from a 2-point adjustment. Test CVMs were tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.
7.1.2 Stability Acceptance Criteria Summary:
The Acceptance Criteria for the Third Generation TSH 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 ±10% of assigned dose for CVM level 2, ±12% of assigned dose for level 3 and ±16% of assigned dose for 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 CVM level 2, ±12% for level 3 and ±16% for level 4 then additional data review is conducted using part 2 criteria. The acceptance criterion is summarized in Table 3.
Table 3: Acceptance criteria for stability of IMMULITE 2000 Third Generation TSH CVM
| CVM level | AssignedDose(µIU/mL) | Guideline Criteria% difference to assigneddose | Acceptable dose range(µIU/mL) | ReviewLimits |
|---|---|---|---|---|
| LTSCVM1 | 0 | Not Applicable | Not Applicable | Controls arewithin 2SDof target oneach curve |
| LTSCVM2 | 0.58 | ±10% | 0.52 - 0.64 | Controls arewithin 2SDof target oneach curve |
| LTSCVM3 | 4.33 | ±12% | 3.81 - 4.85 | Controls arewithin 2SDof target oneach curve |
| LTSCVM4 | 75 | ±16% | 63.00 - 87.00 | Controls arewithin 2SDof target oneach curve |
7.2 Traceability:
The IMMULITE Third Generation TSH CVMs are traceable to WHO 2nd IRP 80/558. The CVMs are manufactured using qualified materials and measurement procedures.
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7.3 Value Assignment:
Third Generation TSH CVMs are 4 level materials which are a subset of 15 level Third Generation TSH calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Third Generation TSH 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 human TSH antigen spiked in Equine Serum matrix with preservatives. Seven levels of commercially available controls and 30 samples (10 spiked patient samples, 15 spiked normal samples and 5 normal samples were used to validate calibrator/CVM value assignments.
The CVMs are manufactured using qualified materials and measurement procedures. The calibrators/CVMs were tested on 15 replicates in total comprised of 5 runs, 3 replicates per run, on 5 systems and 5 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.
7.4 Expected Values/Reference Range:
Each CVM level was tested on 15 replicates in total comprised of 5 runs, 3 replicates per run, on 5 systems and 5 different reagent kit lots. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mcan and ± 2 Standard Deviation (SD). The expected values are provided in the 1MMULITE® 2000 CVM Calibration Verification Material lot-specific package insert The expected assay range is 0.004 - 75 uIU/mL. The target values in Table 4 can be considered as guidelines.
| Analyte targetlevels | CVM Level | Target(µIU/mL) | StandardDeviation(SD) | Guideline ±2SDRange(µIU/mL) |
|---|---|---|---|---|
| CVM1 | 0.000 | - | 0.000 0.004 | |
| CVM2 | 0.580 | 0.032 | 0.516 0.644 | |
| CVM3 | 4.33 | 0.26 | 3.81 4.85 | |
| CVM4 | 75.0 | 6.0 | 63.0 87.0 | |
| Assay Range | 0.004 - 75 µIU/mL |
| Table 4: Target Values | ||
|---|---|---|
| -- | -- | ------------------------ |
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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: 8.
The IMMULITE® 2000 Third Generation TSH Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 Insulin Calibration Verification 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, the IMMULITE® 2000 Third Generation TSH 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: _
| 1. Submitter | Siemens Healthcare Diagnostics Inc. |
|---|---|
| Mailing Address: | 511 Benedict AvenueTarrytown, NY 10591 |
| Contact Person: | Asha Gartland |
| Technical Regulatory Affairs Specialist | |
| Phone Number: | (914)-524-3257 |
| Fax Number: | (914)-524-2101 |
| E-mail Address: | asha.gartland@siemens.com |
| Date Prepared: | January 31, 2014 |
| 2. Device Name | IMMULITE® 2000 Intact PTH Calibration Verification |
| Proprietary Name: | Material |
| Measurand: | Quality Control materials for IMMULITE® 2000 Intact PTH assay |
| Type of Test: | Calibration Verification Material (CVM) for IMMULITE® 2000Intact PTH 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 | IMMULITE® 2000 Insulin Calibration Verification Material(CVM) K133128 |
| Predicate 510(k) No: | |
| 4. Device Description: | The Calibration Verification Material (CVM) contains one set offour vials, with 4 mL for CVM1 and 2 mL each for CVM2, CVM3and CVM4 after reconstitution. CVM1 contains a buffered bovineprotein matrix with preservatives. CVM2, CVM3 and CVM4contain various levels of lyophilized synthetic human intact PTHin buffered bovine protein matrix with preservatives. |
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Comparison with Predicate:
See Indications for Use Statement below 5. Intended Use: Indication for Use: The IMMULITE® Intact PTH Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Intact PTH assay on the IMMULITE 2000 systems Special Conditions for For prescription use only Use Statement(s): IMMULITE® 2000 Systems Special Instrument Requirements: A comparison of the device features, intended use, and other 6. Technological information demonstrates that the IMMULITE® 2000 Intact PTH Characteristics and Calibration Verification Material (CVM) is substantially Substantial Equivalence equivalent to the predicate device as summarized in Table 1.
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Table 1: Substantial Equivalence Comparison
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 Intact PTH CVM | Predicate DeviceIMMULITE 2000 Insulin CVM | |
| IntendedUse | The IMMULITE® Intact PTH CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration of the IMMULITE Intact PTHassay on the IMMULITE 2000 systems. | The IMMULITE® InsulinCalibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration ofthe IMMULITE Insulin assay on theIMMULITE 2000 systems. |
| Form | Lyophilized | Same |
| Levels | 4 | Same |
| Stability | Stable unopened until the expiration date | Same |
| Use | Single Use Only | Same |
| Storage | <20°C | Same |
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 Intact PTH CVM | Predicate DeviceIMMULITE 2000 Insulin CVM | |
| Analyte | Intact PTH | Insulin |
| Matrix | Buffered Bovine/protein withpreservatives | Equine 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 intended use. The following tests were performed on the candidate device.
7.1 Stability Summary:
The real time stability study was conducted to validate shelf life claim and In-Use (Open Component or open vial) claim for the IMMULITE 2000 Intact PTH Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM before and after opening.The IMMULITE® 2000 Intact PTH Calibration Verification Materials (CVMs) are stable up to 2 years when stored at -20℃ prior to opening, and stable for 8 hours at ambient or room temperature (15-25°C) after reconstitution.
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7.1.1 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) at the time points shown in Table 2 and the dose value determined from the reference calibrator curve.
| CVM Level | Time-Points (Days) | |||
|---|---|---|---|---|
| LPDCVM1 | 1 | 182 | 365 | 730 |
| LPDCVM2 | 1 | 182 | 365 | 730 |
| LPDCVM3 | 1 | 182 | 365 | 730 |
| LPDCVM4 | 1 | 182 | 365 | 730 |
Table 2: Stability Time Points
For Open Component testing, the results are determined from a 2-point adjustment. Test CVMs were tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.
7.1.2 Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE Intact PTH Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of the guideline acceptance criteria which require dose value of stability calibrator/CVM to fall between ±12% of assigned dose for CVM level 2, ±8% of assigned dose for CVM level 3 and ±12% 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 ±12% for level 2, ±8% for level 3 and ±12% for level 4, then additional data review is conducted using part 2 criteria.
The acceptance criterion is summarized in Table 3.
Table 3: Acceptance criteria for stability of IMMULITE 2000 Intact PTH CVM
| CVM level | AssignedDose(pg/mL) | *Guideline Criteria% difference toassigned dose | Acceptable doserange (pg/mL) | ReviewLimits |
|---|---|---|---|---|
| LPPCVM1 | 0.00 | Not Applicable | Not Applicable | Controls are |
| LPPCVM2 | 15.2 | ±12% | 13.4 - 17.0 | within 2SD |
| LPPCVM3 | 154 | ±8% | 141.7 - 166.3 | of target on |
| LPPCVM4 | 3784 | ±12% | 3329.9 - 4238.1 | each curve |
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7.2 Traceability:
The IMMULITE Intact PTH CVMs are traceable to internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.
7.3 Value Assignment:
Intact PTH CVMs are 4 level materials which are a subset of 9 level Intact PTH calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Intact PTH reagents and two point adjustors.
The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared synthetic Human Intact PTH (1-84) spiked in the buffered bovine protein matrix. Two levels of commercially available controls and 88 samples (32 EDTA plasma, 32 serum, 12 EDTA dialysis samples and serum dialysis samples) are used to validate calibrator/CVM value assignments.
The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of 9 runs, 7 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. 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.
7.4 Expected Values/Reference Range:
Each CVM level was tested on 27 replicates in total comprised of 9 runs, 7 systems and 3 different reagent kit lots. 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 lotspecific package insert. The expected assay range is 1-2500 pg/mL. The target values in Table 4 can be considered as guidelines.
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Table 4: Target Values
| Analyte targetlevels | CVM Level | Target Mean(pg/mL) | StandardDeviation(SD) | Guideline ±2SD Range(pg/mL) |
|---|---|---|---|---|
| CVM1 | 0.00 | - | 0.00 - 3.00 | |
| CVM2 | 20.4 | 1.35 | 17.7 - 23.1 | |
| CVM3 | 167 | 15.0 | 137 - 197 | |
| CVM4 | 5176 | - | - | |
| (50% CVM1 +50% CVM4) | 2588 | 155.5 | 2277 - 2899 | |
| Assay Range | 1-2500 pg/mL |
CVM4 requires dilution to ensure the target value is within +10% of the top of the reportable range of the assay
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 Intact PTH Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 Insulin Calibration Verification 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, the IMMULITE® 2000 Intact PTH 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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Image /page/18/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles three overlapping, curved shapes, possibly representing human figures or abstract forms. The logo is black and white and appears to be a scanned or printed image.
Food and Drug Administration 1 0903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 March 5, 2014
SIEMENS HEALTHCARE DIAGNOSTICS, INC. ASHA GARTLAND TECHNICAL REGULATORY AFFAIRS SPECIALIST 511 BENEDICT AVENUE TARRYTOWN NY 10591
Re: K140258
Trade/Device Name: IMMULITE® 2000 DHEA-SO4 Calibration Verification Material, IMMULITE® 2000 Third Generation TSH Calibration Verification Material, IMMULITE® 2000 Intact PTH 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: January 31, 2014 Received: February 3, 2014
Dear Asha Gartland:
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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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/ResourcesforYou/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/ReportalProblem/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/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H. Lias -S.
Courtney H. Lias, Ph.D. 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
510(k) Number (if known) K140258
Device Name
MMULITE 2000 DHEA-SO4 Calibration Verification Material, MMULITE 2000 Third Generation TSH Calibration Verification Material, MMULITE 2000 Intact PTH Calibration Verification Material,
Indications for Use (Describe)
The IMMULITE 2000 DHEA-SO4 Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE DHEA-SO4 assay on the IMMULITE 2000 systems.
The IMMULITE 2000 Third Generation Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Third Generation TSH assay on the IMMULITE 2000 systems.
The IMMULITE 2000 Intact PTH Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Intact PTH assay on the IMMULITE 2000 systems.
Type of Use (Select one or both, as applicable)
[ 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)
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FORM FDA 3881 (1/14)
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.
§ 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.