(133 days)
The IMMULITE® 2000 AFP Calibration Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of AFP antigen.
The IMMULITE® BR-MA Calibration Verification Material (CVM) is for in the verification of calibration and reportable range of the IMMULITE BR-MA assay on the IMMULITE 2000 systems
The IMMULITE® OM-MA Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE OM-MA assay on the IMMULITE 2000 systems
The Calibration Verification Material (CVM) contains one set of four vials each 3mL. CVM1 contain bovine serum matrix with preservatives. CVM2, CVM 3 and CVM4 contain low, intermediate and high levels of human source AFP respectively, in a bovine serum matrix with preservatives. CVMs are supplied frozen in a liquid form.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM 1 contains a bovine serum matrix with preservatives. CVM2. CVM3 and CVM4 contain low, intermediate and high levels of human source CA 15-3 in a bovine serum matrix with preservatives. CVMs are supplied frozen in liquid form. In addition to using the CVM at their manufactured concentrations, alternate concentrations may be obtained by accurately diluting the assay-specific calibrator levels with each other.
The Calibration Verification Material (CVM) contains one set of four vials. 2 mL each. CVM 1 contains a bovine protein/buffer matrix with preservatives. CVM2. CVM3 and CVM4, contain low, intermediate and high levels of CA 125 in a bovine protein/buffer matrix with preservatives. CVMs are supplied in Iyophilized form.
This document describes the validation of three Calibration Verification Materials (CVMs): IMMULITE® 2000 OM-MA CVM, IMMULITE® 2000 BR-MA CVM, and IMMULITE® 2000 AFP CVM. Each CVM's acceptance criteria and performance study are outlined below.
IMMULITE® 2000 OM-MA Calibration Verification Material (CVM)
1. Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Part 1 - Guideline) | Follow-up Criteria (Part 2 - Review Limits) | Reported Performance (Dose Value) |
|---|---|---|---|
| CVM1 (LOPCVM1) | (Implicitly, stable at 0.00 U/mL) | Within 2SD of control target value | Not explicitly stated for performance, but target mean is 0.00 U/mL |
| CVM2 (LOPCVM2) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 7.70 U/mL |
| CVM3 (LOPCVM3) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 57.0 U/mL |
| CVM4 (LOPCVM4) | Within ±11% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 609 U/mL |
| (85% CVM4 + 15% CVM1) | (Within ±10% of reportable range for CVM4 dilution) | (Within ±10% of reportable range for CVM4 dilution) | Not explicitly stated, but target mean is 518 U/mL |
2. Sample Size and Data Provenance
- Test Set Sample Size: 27 replicates for each CVM level, comprised of 9 runs and 3 replicates per run.
- Data Provenance: The study was conducted internally by Siemens Healthcare Diagnostics Inc. No country of origin for the data is specified beyond that. The study appears to be prospective in nature for stability testing.
3. Number of Experts and Qualifications for Ground Truth
- Not applicable. This device is a calibration verification material for an in vitro diagnostic assay. Ground truth is established through internal assigned reference calibrators and gravimetrically prepared internal material, not expert consensus.
4. Adjudication Method for Test Set
- Not applicable. Performance is based on quantitative measurements against predefined criteria.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. This is a calibration verification material, not an AI-assisted diagnostic tool for human readers.
6. Standalone Performance
- Yes, a standalone performance study was conducted in the form of stability testing and value assignment. The CVMs were tested independently on IMMULITE 2000 systems.
7. Type of Ground Truth Used
- Internal assigned reference calibrators prepared using OM-MA antigen stock solution.
- Internal material that is gravimetrically prepared.
- Value assignment was validated using commercially available controls and patient samples (5 normal, 25 normal spiked with high patient sample).
8. Sample Size for Training Set
- Not applicable in the typical sense of a 'training set' for a machine learning algorithm. The "value assignment" process involves generating curves from assigned reference calibrators and testing on multiple replicates. This is more akin to a robust characterization and validation process rather than machine learning training.
9. How Ground Truth for Training Set was Established
- Not applicable. The "ground truth" for the calibrators is established through their preparation (OM-MA antigen stock solution, gravimetric preparation) and characterization against reference materials.
IMMULITE® 2000 BR-MA Calibration Verification Material (CVM)
1. Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Part 1 - Guideline) | Follow-up Criteria (Part 2 - Review Limits) | Reported Performance (Dose Value) |
|---|---|---|---|
| CVM1 (LBRCVM1) | (Implicitly, stable at 0.00 U/mL) | Within 2SD of control target value | Not explicitly stated for performance, but target mean is 0.00 U/mL |
| CVM2 (LBRCVM2) | Within ±15% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 18.8 U/mL |
| CVM3 (LBRCVM3) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 165 U/mL |
| CVM4 (LBRCVM4) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 291 U/mL |
2. Sample Size and Data Provenance
- Test Set Sample Size: 27 replicates for each CVM level, comprised of 9 runs and 3 replicates per run.
- Data Provenance: The study was conducted internally by Siemens Healthcare Diagnostics Inc. No country of origin for the data is specified beyond that. The study appears to be prospective in nature for stability testing.
3. Number of Experts and Qualifications for Ground Truth
- Not applicable. This device is a calibration verification material for an in vitro diagnostic assay. Ground truth is established through internal assigned reference calibrators and gravimetrically prepared internal material, not expert consensus.
4. Adjudication Method for Test Set
- Not applicable. Performance is based on quantitative measurements against predefined criteria.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. This is a calibration verification material, not an AI-assisted diagnostic tool for human readers.
6. Standalone Performance
- Yes, a standalone performance study was conducted in the form of stability testing and value assignment. The CVMs were tested independently on IMMULITE 2000 systems.
7. Type of Ground Truth Used
- Internal assigned reference calibrators prepared using BR-MA antigen stock solution.
- Internal material that is gravimetrically prepared.
- Value assignment was validated using commercially available controls and patient samples (5 normal, 25 spiked patient samples).
8. Sample Size for Training Set
- Not applicable in the typical sense of a 'training set' for a machine learning algorithm. The "value assignment" process involves generating curves from assigned reference calibrators and testing on multiple replicates. This is more akin to a robust characterization and validation process rather than machine learning training.
9. How Ground Truth for Training Set was Established
- Not applicable. The "ground truth" for the calibrators is established through their preparation (BR-MA antigen stock solution, gravimetric preparation) and characterization against reference materials.
IMMULITE® 2000 AFP Calibration Verification Material (CVM)
1. Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Part 1 - Guideline) | Follow-up Criteria (Part 2 - Review Limits) | Reported Performance (Dose Value) |
|---|---|---|---|
| CVM1 (LAPCVM1) | (Implicitly, stable at 0.00 IU/mL) | Within 2SD of control target value | Not explicitly stated for performance, but target mean is 0.00 IU/mL |
| CVM2 (LAPCVM2) | Within ±15% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 3.03 IU/mL |
| CVM3 (LAPCVM3) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 47.9 IU/mL |
| CVM4 (LAPCVM4) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 413 IU/mL |
| (75% CVM4 + 25% CVM1) | (Within ±10% of reportable range for CVM4 dilution) | (Within ±10% of reportable range for CVM4 dilution) | Not explicitly stated, but target mean is 310 IU/mL |
2. Sample Size and Data Provenance
- Test Set Sample Size: 27 replicates for each CVM level, comprised of 9 runs and 3 replicates per run.
- Data Provenance: The study was conducted internally by Siemens Healthcare Diagnostics Inc. No country of origin for the data is specified beyond that. The study appears to be prospective in nature for stability testing.
3. Number of Experts and Qualifications for Ground Truth
- Not applicable. This device is a calibration verification material for an in vitro diagnostic assay. Ground truth is established through traceability to WHO 1st IS 72/225 and qualified internal materials, not expert consensus.
4. Adjudication Method for Test Set
- Not applicable. Performance is based on quantitative measurements against predefined criteria.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. This is a calibration verification material, not an AI-assisted diagnostic tool for human readers.
6. Standalone Performance
- Yes, a standalone performance study was conducted in the form of stability testing and value assignment. The CVMs were tested independently on IMMULITE 2000 systems.
7. Type of Ground Truth Used
- Traceable to WHO 1st IS 72/225.
- Manufactured using qualified materials and measurement procedures.
- Value assignment was validated using commercially available controls and 61 samples (amniotic fluid samples, pregnancy trimester samples, normal patient samples, and spiked AFP samples).
8. Sample Size for Training Set
- Not applicable in the typical sense of a 'training set' for a machine learning algorithm. The "value assignment" process involves generating curves from assigned reference calibrators and testing on multiple replicates. This is more akin to a robust characterization and validation process rather than machine learning training.
9. How Ground Truth for Training Set was Established
- Not applicable. The "ground truth" for the calibrators is established through traceability to WHO 1st IS 72/225 and their preparation using qualified materials and measurement procedures.
{0}------------------------------------------------
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: K132739
-
- Submitter Mailing Address:
8
- Submitter Mailing Address:
Contact Person:
Phone Number: Fax Number: E-mail Address: Date Prepared:
-
- Device Name Proprietary Name: Measurand: Type of Test:
Regulation Section: Classification: Products Code: Panel:
- Device Name Proprietary Name: Measurand: Type of Test:
-
- Predicate Device Name Predicate 510(k) No:
-
- Device Description:
-
- Intended Use: Indication for Use:
Special Conditions for Use Statement(s): Special Instrument Requirements:
Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591
Garo Mimaryan, MS, RAC Senior Regulatory Affairs Specialist (914)-524-3270 (914)-524-2101 garo.mimarvan@siemens.com January 8, 2014
IMMULITE® 2000 OM-MA Calibration Verification Material Quality Control materials for IMMULITE® 2000 OM-MA assay Calibration Verification Material (CVM) for IMMULITE® 2000 OM-MA assay 21 CFR 862.1660, Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)
Elecsys CA 125 II CalCheck 5 K102086
The Calibration Verification Material (CVM) contains one set of four vials. 2 mL each. CVM 1 contains a bovine protein/buffer matrix with preservatives. CVM2. CVM3 and CVM4, contain low, intermediate and high levels of CA 125 in a bovine protein/buffer matrix with preservatives. CVMs are supplied in Iyophilized form.
See Indications for Use Statement below
The IMMULITE® OM-MA Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE OM-MA assay on the IMMULITE 2000 systems
For prescription use only
IMMULITE® 2000 Systems
{1}------------------------------------------------
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 OM-MA Calibration Verification Material (CVM) is substantially equivalent to the predicate device, as summarized in Table 1.
Table 1: Substantial Equivalence Comparison
| SIMILARITIES | |||
|---|---|---|---|
| Candidate DeviceIMMULITE 2000 OM-MA CVM | Predicate DeviceElecsys CA 125 II CalCheck 5 | ||
| IntendedUse | The IMMULITE® OM-MA CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration and reportable range of theIMMULITE OM-MA assay on theIMMULITE 2000 systems. | The Elecsys CA 125 II CalCheck 5 isan assayed control for use incalibration verification and for use inthe verification of the assay rangeestablished by the Elecsys CA 125 11reagent on the indicated Elecsys andcobas e immunoassay analyzers, forin vitro diagnostic use only | |
| Analyte | CA 125 | Same | |
| Form | Lyophilized | Same | |
| Stability | Stable until the expiration date whenstored refrigerated. | Same | |
| Storage | 2-8°C | Same | |
| DIFFERENCES | |||
| Candidate DeviceIMMULITE 2000 OM-MA CVM | Predicate DeviceElecsys CA 125 II CalCheck 5 | ||
| Matrix | Bovine serum | Level 1: Equine serumLevels 2-5 : Human serum | |
| Use | Single Use Only | Not For Single Use |
7. Non-Clinical Performance Testing
Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.
Stability Summary:
The stability study was conducted to validate shelf life claim for the IMMULITE 2000 OM-MA Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 OM-MA Calibration Verification Materials (CVMs) are stable up to 9 years when stored refrigerated at 2-8°C prior to opening.
Stability Protocol Summary:
The CVM study protocols are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) and the dose value determined from the reference calibrator curve and is summarized in Table 2.
{2}------------------------------------------------
| CVM Level | Time-Points(Days) | |||
|---|---|---|---|---|
| LOPCVM1 | 1 | 1825 | 2555 | 3285 |
| LOPCVM2 | 1 | 1825 | 2555 | 3285 |
| LOPCVM3 | 1 | 1825 | 2555 | 3285 |
| LOPCVM4 | 1 | 1825 | 2555 | 3285 |
Table 2: Stability Protocol Summary
Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE OM-MA Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of the Guideline acceptance criteria which require dose value of stability CVM to fall between ±10% of assigned dose for CVM levels 2 to 3 and ±11% 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% of assigned dose for CVM levels 2 to 3 and ±11% of assigned dose for CVM level 4, then additional data review is conducted using part 2 criteria.
Traceability:
The IMMULITE OM-MA CVMs are traceable to internal assigned reference calibrators prepared using OM-MA antigen stock solution and are traceable to internal material which is gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.
Value Assignment:
OM-MA CVMs are 4 level materials which are a subset of 9 level OM-MA calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of OM-MA reagents and two point adjustors. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems, Three levels of commercially available controls and 30 samples (5 normal patient samples and 25 normal patients spiked with high patient sample) were used to validate CVM value assignments
The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of nine runs and three replicates per run on nine systems and three 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
{3}------------------------------------------------
Expected 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 9 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific value card. The expected assay range is 2-500 U/mL. The target values in Table 3 can be considered as guidelines.
| Analyte targetlevels | CVM Levels | Target Mean(U/mL) | SD | Guideline ±2SD Range(U/mL) | |
|---|---|---|---|---|---|
| CVM1 | 0.00 | - | 0.00 | ≤2.00 | |
| CVM2 | 7.70 | 0.845 | 6.01 | 9.39 | |
| CVM3 | 57.0 | 2.85 | 51.3 | 62.7 | |
| CVM4 | 609 | - | - | - | |
| (85% of CVM4 +15% of CVM1)* | 518 | 28.5 | 461 | 575 | |
| Assay Range | 2 -500 U/mL |
Table 3: Target Values
*Note: CVM4 requires dilution to ensure the target value is within +10% 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
ರಿ. Conclusion:
OM-MA Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Elecsys CA 125 II CalCheck 5. 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 OM-MA Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.
{4}------------------------------------------------
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: K132739
-
- Submitter Mailing Address:
Contact Person:
Phone Number: Fax Number: E-mail Address: Date Prepared:
-
- Device Name Proprietarv Name: Measurand: Type of Test:
Regulation Section: Classification: Products Code:
- Device Name Proprietarv Name: Measurand: Type of Test:
Panel:
-
- Predicate Device Name Predicate 510(k) No:
-
- Device Description:
-
- Intended Use: . Indication for Use:
Special Conditions for Use Statement(s): Special Instrument Requirements:
Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591
Garo Mimaryan, MS, RAC . Senior Regulatory Affairs Specialist (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com January 8, 2014
IMMULITE® 2000 BR-MA Calibration Verification Material Quality Control materials for IMMULITE® 2000 BR-MA assay Calibration Verification Material (CVM) for IMMULITE® 2000 BR-MA assay 21 CFR 862.1660, Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)
Elecsys CA 15-3 II CalCheck 5 K122242
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM 1 contains a bovine serum matrix with preservatives. CVM2. CVM3 and CVM4 contain low, intermediate and high levels of human source CA 15-3 in a bovine serum matrix with preservatives. CVMs are supplied frozen in liquid form. In addition to using the CVM at their manufactured concentrations, alternate concentrations may be obtained by accurately diluting the assay-specific calibrator levels with each other.
See Indications for Use Statement below The IMMULITE® BR-MA Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE BR-MA assay on the IMMULITE 2000 systems
For prescription use only
{5}------------------------------------------------
6. 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 BR-MA Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 BR-MA CVM | Predicate Device :Elecsys CA 15-3 II CalCheck 5 | |
| IntendedUse | The IMMULITE® BR-MA CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration and reportable range of theIMMULITE BR-MA assay on theIMMULITE 2000 systems | The Elecsys CA 15-3 II CalCheck 5is an assayed control for use incalibration verification and for use inthe verification of the assay rangeestablished by the Elecsys CA 15-3 IIreagent on the indicated Elecsys andcobas e immunoassay analyzers. Forin vitro diagnostic use only. |
| Analyte | CA 15-3 | Same |
| DIFFERENCES | ||
| Candidate DeviceIMMULITE 2000 BR-MA CVM | Predicate Device :Elecsys CA 15-3 II CalCheck 5 | |
| Form | Liquid | Lyophilized |
| Matrix | Bovine serum | Level 1: Equine serum matrixLevels 2-5 : Human serum matrix |
| Stability | Stable until the expiration date whenstored frozen | Stable until the expiration date whenstored refrigerated. |
| Storage | -20°C | 2-8°C |
| Use | Single Use Only | Not For Single Use |
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 shelf life claim for the IMMULITE 2000 BR-MA Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 BR-MA Calibration Verification Materials (CVMs) are stable up to 4.5 years when stored refrigerated at -20°C prior to opening.
{6}------------------------------------------------
Stability Protocol Summary:
The CVM study protocols are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) and the dose value determined from the reference calibrator curve and is summarized in Table 2.
| CVM Level | Time-Points(Days) | |||
|---|---|---|---|---|
| LBRCVM1 | 1 | 730 | 912 | 1095 |
| LBRCVM2 | 1 | 730 | 912 | 1095 |
| LBRCVM3 | 1 | 730 | 912 | 1095 |
| LBRCVM4 | 1 | 730 | 912 | 1095 |
Table 2: Stability Protocol Summary
Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE BR-MA Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of the Guideline acceptance criteria which require dose value of stability CVM to fall between ±15% of assigned dose for CVM level 2 and ±10% of assigned dose for CVM levels 3 and 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% of assigned dose for CVM level 2 and ±10% of assigned dose for CVM levels 3 and 4, then additional data review is conducted using part 2 criteria.
Traceability:
The IMMULITE BR-MA CVMs are traceable to internal assigned reference calibrators prepared using BR-MA antigen stock solution and are traceable to internal material which is gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures
Value Assignment:
BR-MA CVMs are 4 level materials which are a subset of 7 level BR-MA calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of BR-MA reagents and two point adjustors. 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, Six levels of commercially available controls and 30 samples (5 normal patient samples and 25 spiked patient samples) were used to validate CVM value assignments.
The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of 9 runs and three replicates per run on 6 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}------------------------------------------------
Expected 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 6 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific value card. The expected assay range is 1-300 IU/mL. The target values in Table 3 can be considered as guidelines.
| Analytetarget levels | Level | Target Mean(U/mL) | SD | Guideline ±2SD Range(U/mL) | |
|---|---|---|---|---|---|
| 1 | 0.00 | - | 0.00 | ≤1.00 | |
| 2 | 18.8 | 1.4 | 16.0 | 21.6 | |
| 3 | 165 | 8.25 | 149 | 182 | |
| 4 | 291 | 14.5 | 262 | 320 | |
| Assay Range | 1-300 U/mL |
Table 3: 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
9. Conclusion:
/
BR-MA Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Elecsvs CA 15-3 II CalCheck 5. 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 BR-MA Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.
{8}------------------------------------------------
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.
K132739 The assigned 510(k) Number:
-
- Submitter Mailing Address:
.
- Submitter Mailing Address:
Contact Person:
Phone Number: Fax Number: E-mail Address: Date Prepared:
-
- Device Name Proprietary Name: Measurand: Type of Test:
Regulation Section: Classification: Products Code:
- Device Name Proprietary Name: Measurand: Type of Test:
Panel:
-
Predicate Device Name Predicate 510(k) No:
-
Device Description:
-
- Intended Use: Indication for Use:
Special Conditions for Use Statement(s): Special Instrument Requirements:
- Intended Use: Indication for Use:
Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591
Garo Mimaryan, MS, RAC Senior Regulatory Affairs Specialist (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com January 8, 2014
IMMULITE® 2000 AFP Calibration Verification Material Quality Control materials for IMMULITE® 2000 AFP assay Calibration Verification Material (CVM) for IMMULITE® 2000 AFP assay 21 CFR 862.1660, Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)
IMMULITE/IMMULITE 1000 Third Generation PSA CVM K122534
The Calibration Verification Material (CVM) contains One set of four vials each 3mL. CVM1 contain bovine serum matrix with preservatives. CVM2, CVM 3 and CVM4 contain low, intermediate and high levels of human source AFP respectively, in a bovine serum matrix with preservatives. CVMs are supplied frozen in a liquid form.
See Indications for Use Statement below The IMMULITE® 2000 AFP Calibration Verification Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of AFP antigen.
For prescription use only
IMMULITE® 2000 Systems
For prescription use only
{9}------------------------------------------------
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 AFP Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 AFP CVM | Predicate DeviceIMMULITE/IMMULITE 1000Third Generation PSA CVM | |
| IntendedUse | The IMMULITE® 2000 AFPCalibration Verification Material(CVM) is intended for monitoringsystem performance of the IMMULITEImmunoassay system for thequantitative measurement of AFPantigen. | The IMMULITE®/IMMULITE 1000Third Generation PSA CalibrationVerification Material (CVM) isintended for monitoring systemperformance of the IMMULITEImmunoassay system for thequantitative measurement of PSAantigen. |
| Form | Liquid | Same |
| stability | Stable until the expiration date whenstored frozen | Same |
| Storage | -20°C | Same |
| Use | Single Use Only | Same |
| Table 1: Substantial Equivalence Comparison | |
|---|---|
| --------------------------------------------- | -- |
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 AFP CVM | Predicate DeviceIMMULITE/IMMULITE 1000Third Generation PSA CVM | |
| Analyte | AFP | PSA |
| Matrix | Bovine serum | Chicken serum |
| AssayRange | 0.2–300 IU/mL | 0.015 — 20 ng/mL |
7. Non-Clinical Performance Testing
Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.
Stability Summary:
The stability study was conducted to validate shelf life claim for the IMMULITE 2000 AFP Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 AFP Calibration Verification Materials (CVMs) are stable up to 3.5 years when stored refrigerated at -20°C prior to opening.
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Stability Protocol Summary:
The CVM study protocols are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) and the dose value determined from the reference calibrator curve and is summarized in Table 2.
| CVM Level | Time-Points(Days) | |||
|---|---|---|---|---|
| LAPCVM1 | 1 | 912 | 1095 | 1460 |
| LAPCVM2 | 1 | 912 | 1095 | 1460 |
| LAPCVM3 | 1 | 912 | 1095 | 1460 |
| LAPCVM4 | 1 | 912 | 195 | 1460 |
Table 2: Stability Protocol Summary
Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE AFP Calibration Material (CVM) are in 2 parts. Part 1 consists of the Guideline acceptance criteria which require dose value of stability CVM to fall between ±15% of assigned dose for CVM levels 2 and ±10% of assigned dose for CVM levels 3 and 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% of assigned dose for CVM levels 2 and ±10% of assigned dose for CVMs 3 and 4, then additional data review is conducted using part 2 criteria.
Traceability:
The IMMULITE AFP CVMs are traceable to WHO 1st IS 72/225 and are manufactured using qualified materials and measurement procedures.
Value Assignment:
IMMULITE® 2000 AFP (Alpha-fetoprotein) Calibration Materials are 4 level materials which are a subset of 9 level AFP calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of AFP reagents and two point adjustors. 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. Nine levels of commercially available controls and 61 samples including amniotic fluid samples, pregnancy trimester samples, normal patient samples and spiked AFP samples were used to validate CVM value assignments.
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. The controls must fall within their target ranges
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Expected Values/Reference Range:
Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run. 3 different reagent kit lots and 5 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific value card. The expected assay range is 0.2 -300 IU/mL. The target values in Table 3 can be considered as guidelines.
| Target Values | Table 3: | ||||||
|---|---|---|---|---|---|---|---|
| --------------- | ---------- | -- | -- | -- | -- | -- | -- |
| Analyte target levels | CVM Level | Target Mean (IU/mL) | SD | Guideline ±2SD Range (IU/mL) |
|---|---|---|---|---|
| CVM1 | 0.00 | - | 0.00 $≤$ 0.20 | |
| CVM2 | 3.03 | 0.225 | 2.58 - 3.48 | |
| CVM3 | 47.9 | 2.4 | 43.1 - 52.7 | |
| CVM4 | 413 | - | - | |
| (75% CVM4 + 25% CVM1) | 310 | 15.5 | 279 - 341 |
*Note: CVM4 requires dilution to ensure that the target value is within the +10% 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
9. Conclusion:
IMMULITE® 2000 AFP (Alpha-fetoprotein) Calibration Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed IMMULITE 1000 Third Generation PSA CVM. 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 AFP 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/12/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion around the symbol. The text is in all caps and appears to be in a sans-serif font. The logo is black and white.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
January 14, 2014
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G60 Silver Spring, MD 20993-0002
Siemens Healthcare Diagnostics Inc. c/o Mr. Garo Mimaryan Technical Regulatory Affairs Specialist III 511 Benedict Avenue Tarrytown, NY 10591
Re: K132739
Trade/Device Name: IMMULITE® 2000 AFP Calibration Verification Material IMMULITE® 2000 BR-MA Calibration Verification Material IMMULITE® 2000 OM-MA Calibration Verification Material Regulation Number: 21 CFR §862.1660 Regulation Name: Quality Control Material (assayed and unassayed) Regulatory Class: I Product Code: JJX Dated: December 13, 2013 Received: December 16, 2013
Dear Mr. Mimaryan:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical
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Page 2 - Mr. Garo Mimaryan
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 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 regulation (21 CFR Part 801), please contact the Division of Small Manufacturers. International and Consumer Assistance at its tollfree 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/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours,
Leonthenal Rivarrington -S
Maria M. Chan, Ph.D. for Director
Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health
Center for Devices and Radiological Health
Enclosure
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.
510(k) Number (if known) K132739
Device Name
IMMULITE® 2000 AFP Calibration Verification Material
Indications for Use (Describe)
The IMMULITE® 2000 AFP Calibration Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of AFP antigen.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
THE THE FORT AND FOR FOR FOR FOR FOR FOR FOR ಿಗೆ ಸೇರಿ
Concurrence of Center for Devices and Radiological Health (CDRH) (Signalure)
Image /page/14/Picture/14 description: The image shows the name "Elizabeth ADSstafford -S" in black font. The letters "ADS" are stylized with a pattern of lines. The rest of the name is in a simple, sans-serif font.
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on fast page.
510(k) Number (if known) K132739
Device Name
.. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
IMMULITE® 2000 BR-MA Calibration Verification Material
Indications for Use (Describe)
The IMMULITE® BR-MA Calibration Verification Material (CVM) is for in the verification of calibration and reportable range of the IMMULITE BR-MA assay on the IMMULITE 2000 systems
Type of Use (Select one or both, as applicable)
🇿 Prescription Use (Part 21 CFR 801 Subpart D)
O Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR F િયારે કુલ ૧૯ મિત
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
Image /page/15/Picture/14 description: The image shows the name "Elizabeth Stafford -S" in a bold, sans-serif font. The letters "FA" are stylized and placed between "Elizabeth" and "Stafford". The text is black against a white background, creating a high contrast.
FORM FDA 3881 (1/14)
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.
510(k) Number (if known) K132739
Device Name
IMMULITE® 2000 OM-MA Calibration Verification Material
Indications for Use (Describe)
The IMMULITE® OM-MA Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE OM-MA assay on the IMMULITE 2000 systems
Type of Use (Select one or both, as applicable)
[X] Prescription Use (Part 21 CFR 801 Subpart D)
[] Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR 11 - 120 - 120 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 ..
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
Image /page/16/Picture/14 description: The image shows the name "Elizabeth-A-Stafford-S" in a bold, sans-serif font. The letters are black against a white background. The letters "A" is stylized with a circular design around it.
:
§ 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.