(28 days)
IMMULITE® 2000 Beta-2 Microglobulin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Beta-2 Microglobulin assay on the IMMULITE 2000 systems
IMMULITE® 2000 High Sensitivity CRP Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE High Sensitivity CRP assay on the IMMULITE 2000 systems
The IMMULITE® 2000 Beta-2 Microglobulin Calibration Verification Material (CVM) contains one set of four vials each 3mL. CVM1 contains bovine protein buffer matrix with preservatives and CVM2, CVM3, and CVM4 contain various levels of human Beta-2 Microglobulin in a lyophilized bovine protein buffer matrix with preservatives.
The IMMULITE® 2000 High Sensitivity CRP Calibration Verification Material (CVM) contains one set of four vials, 2mL each. CVM1 contains a bovine protein/buffer with 0.098% sodium azide and preservative. CVM2, CVM3, and CVM4 contain various levels of human CRP in a bovine protein/buffer with 0.098% sodium azide and preservative.
This document describes two calibration verification materials (CVMs): IMMULITE® 2000 Beta-2 Microglobulin CVM and IMMULITE® 2000 High Sensitivity CRP CVM. Since they are distinct devices with separate studies and acceptance criteria, I will describe them separately.
IMMULITE® 2000 Beta-2 Microglobulin Calibration Verification Material
This device is a quality control material intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Beta-2 Microglobulin assay on the IMMULITE 2000 systems.
1. Acceptance Criteria and Reported Device Performance
The device's performance is demonstrated through stability studies. The acceptance criteria for stability are divided into two parts:
- Part 1: Guideline Acceptance Criteria:
- CVM Level 2: Dose value to fall within ±15% of the assigned dose.
- CVM Level 3 and 4: Dose value to fall within ±20% of the assigned dose.
- Part 2: Review Limits Criteria: If Part 1 criteria are not met, the dose value of the controls must be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve.
The document states that the stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claims. It also reports:
- Real-time shelf life: Stable up to 9 years when stored at -20°C prior to opening. The study for lots 011 and 012 is ongoing until the 119-month time point.
- Open component (in-use) stability: 8 hours of stability at ambient or room temperature (15-25°C) after opening.
The document does not provide a direct table comparing the acceptance criteria to actual numerical results for each CVM level. Instead, it states that the testing demonstrated the device meets the performance specifications.
2. Sample Size and Data Provenance for Test Set
- Sample Size:
- For stability testing, CVMs were run in duplicate (as a minimum) at specified time points. Three lots were used: Lot 010, Lot 011, and Lot 012. Each lot had 4 CVM levels.
- For open component testing, CVM lot 012 was tested using IMMULITE 2000 Beta-2 Microglobulin (L2KBM) kit lot 247 at 2-hourly intervals for up to 9 hours.
- For Expected Values/Target Values/Reference Range establishment: Each CVM level was tested for a total of 15 replicates (5 runs and 3 replicates per run) using 3 different reagent kit lots and 5 IMMULITE 2000 systems.
- Data Provenance: The information does not specify the country of origin of the data. The studies are described as "non-clinical performance testing," implying they are internal validation studies conducted by the manufacturer. The data is prospective as it involves stability testing over time.
3. Number of Experts and Qualifications for Ground Truth
- This device is a calibration verification material. The "ground truth" for CVMs is typically established through precise analytical methods and traceability to reference materials. The document doesn't mention the involvement of "experts" in establishing ground truth in the same way clinical diagnostic devices might have radiologists or pathologists.
- The CVMs are described as traceable to an internal material which has been gravimetrically prepared. Value assignment involves generating dose values using a curve generated by assigned reference calibrators, with values averaged across systems. Quality control is performed by calculating recovery of patient samples (40 samples: 20 spiked and diluted urine, 10 neat urine, 10 diluted serum) and controls.
4. Adjudication Method for Test Set
Not applicable for a calibration verification material's performance studies. The evaluation is based on quantitative measurements against established internal and traceable standards.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is a calibration verification material, not a diagnostic imaging device typically evaluated with MRMC studies comparing human readers with and without AI assistance.
6. Standalone Performance Study
Yes, the studies described are standalone performance studies for the calibration verification material itself. Its performance is evaluated independently against its established criteria and traceability.
7. Type of Ground Truth Used
The ground truth or reference values for the CVMs are established through:
- Traceability: To an internal material gravimetrically prepared.
- Value Assignment: Using assigned reference calibrators and averaging recovered values across systems.
- Validation: Through recovery calculation of patient samples (spiked and diluted urine, neat urine, diluted serum) and controls.
8. Sample Size for the Training Set
Not applicable. This is a calibration verification material; it does not involve machine learning or a "training set" in the conventional sense. The "training" of the assay itself (which these materials verify) would involve its own calibration process, which is distinct from the CVM performance study.
9. How Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of device.
IMMULITE® 2000 High Sensitivity CRP Calibration Verification Material
This device is a quality control material intended for in vitro diagnostic use in the verification of calibration of the IMMULITE High Sensitivity CRP assay on the IMMULITE 2000 systems.
1. Acceptance Criteria and Reported Device Performance
The device's performance is demonstrated through stability studies. The acceptance criteria for stability are divided into two parts:
- Part 1: Guideline Acceptance Criteria:
- CVM Level 2: Dose value to fall within ±20% of the assigned dose.
- CVM Level 3: Dose value to fall within ±6% of the assigned dose.
- CVM Level 4: Dose value to fall within ±10% of the assigned dose.
- Part 2: Review Limits Criteria: If Part 1 criteria are not met, the dose value of the controls must be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve.
The document states that the stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claims. It also reports:
- Real-time shelf life: Stable up to 11 months when stored at 2-8°C prior to opening. The study for lots 025, 026, and 090 is ongoing (up to 23, 12, and 11 months respectively).
- Open component (in-use) stability: 8 hours of stability at ambient or room temperature (15-25°C) after opening.
The document does not provide a direct table comparing the acceptance criteria to actual numerical results for each CVM level. Instead, it states that the testing demonstrated the device meets the performance specifications.
2. Sample Size and Data Provenance for Test Set
- Sample Size:
- For stability testing, CVMs were run in duplicate (as a minimum) at specified time points. Three lots were used: Lot 025, Lot 026, and Lot 090. Each lot had 4 CVM levels.
- For Expected Values/Target Values/Reference Range establishment: CVMs were tested on 15 replicates in total (comprised of 5 runs and 3 replicates per run) on 4 IMMULITE 2000 systems and 3 different reagent kit lots.
- Data Provenance: The information does not specify the country of origin of the data. The studies are described as "non-clinical performance testing," implying they are internal validation studies conducted by the manufacturer. The data is prospective as it involves stability testing over time.
3. Number of Experts and Qualifications for Ground Truth
- Similar to the Beta-2 Microglobulin CVM, this device is a calibration verification material. The "ground truth" for CVMs is typically established through precise analytical methods and traceability to reference materials. The document doesn't mention the involvement of "experts" in establishing ground truth in the same way clinical diagnostic devices might have radiologists or pathologists.
- The CVMs are described as traceable to WHO 1st IS 85/506 and CRM 470. Value assignment involves generating dose values using a curve generated by assigned reference calibrators, with values averaged across systems. Quality control is performed by calculating recovery of patient samples (28 samples: 21 normal, 7 spiked) and controls.
4. Adjudication Method for Test Set
Not applicable for a calibration verification material's performance studies. The evaluation is based on quantitative measurements against established internal and traceable standards.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is a calibration verification material, not a diagnostic imaging device typically evaluated with MRMC studies comparing human readers with and without AI assistance.
6. Standalone Performance Study
Yes, the studies described are standalone performance studies for the calibration verification material itself. Its performance is evaluated independently against its established criteria and traceability.
7. Type of Ground Truth Used
The ground truth or reference values for the CVMs are established through:
- Traceability: To WHO 1st IS 85/506 and CRM 470.
- Value Assignment: Using assigned reference calibrators and averaging recovered values across systems.
- Validation: Through recovery calculation of patient samples (normal and spiked) and controls.
8. Sample Size for the Training Set
Not applicable. This is a calibration verification material; it does not involve machine learning or a "training set" in the conventional sense. The "training" of the assay itself (which these materials verify) would involve its own calibration process, which is distinct from the CVM performance study.
9. How Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of device.
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle with three human profiles incorporated into its design. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle symbol.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 30, 2014
SIEMENS HEALTHCARE DIAGNOSTICS, INC. DONNA VELASQUEZ REGULATORY TECHNICAL SPECIALIST 5210 PACIFIC CONCOURSE DRIVE LOS ANGELES CA 90045
Re: K142878
Trade/Device Name: IMMULITE® 2000 Beta-2 Microglobulin Calibration Verification Material and IMMULITE® 2000 High Sensitivity CRP 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: September 30, 2014 Received: October 02, 2014
Dear Ms. Donna Velasquez:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR 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 Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H. Lias -S
Courtney H. Lias, 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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Indications for Use
510(k) Number (if known) K142878
Device Name
IMMULITE® 2000 Beta-2 Microglobulin Calibration Verification Material
Indications for Use (Describe)
IMMULITE® 2000 Beta-2 Microglobulin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Beta-2 Microglobulin 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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K142878
Device Name IMMULITE® 2000 High Sensitivity CRP Calibration Verification Material
Indications for Use (Describe)
IMMULITE® 2000 High Sensitivity CRP Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE High Sensitivity CRP 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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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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.5210 Pacific Concourse DriveLos Angeles, CA 90045 |
| Contact Person: | Donna VelasquezRegulatory Technical Specialist |
| Phone Number: | (310)-645-8200 x7403 |
| Fax Number: | (310)-645-9999 |
| E-mail Address: | donna.velasquez@siemens.com |
| Date Prepared: | October 28th, 2014 |
| 2. Device Name | |
| Proprietary Name: | IMMULITE® 2000 Beta-2 Microglobulin Calibration VerificationMaterial |
| Measurand: | Quality Control materials for IMMULITE® 2000 Beta-2Microglobulin assay |
| Type of Test: | Calibration Verification Material (CVM) for IMMULITE® 2000Beta-2 Microglobulin 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 Intact PTH Calibration Verification Material(CVM) |
| Predicate 510(k) No: | K140258 |
| 4. Device Description: | The IMMULITE® 2000 Beta-2 Microglobulin CalibrationVerification Material (CVM) contains one set of four vials each3mL. CVM1 contains bovine protein buffer matrix withpreservatives and CVM2, CVM3, and CVM4 contain various levelsof human Beta-2 Microglobulin in a lyophilized bovine proteinbuffer matrix with preservatives. |
| 5. Intended Use:Indication for Use: | See Indications for Use Statement belowThe IMMULITE® 2000 Beta-2 Microglobulin CalibrationVerification Material (CVM) is for in vitro diagnostic use in theverification of calibration of the IMMULITE Beta-2 Microglobulinassay on the IMMULITE 2000 systems |
| Special Conditions forUse Statement(s): | For prescription use only |
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Special Instrument Requirements:
IMMULITE® 2000 Systems
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 Beta-2 Microglobulin 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 Beta-2Microglobulin CVM | Predicate DeviceIMMULITE 2000 Intact PTHCVM | |
| IntendedUse | The IMMULITE® 2000 Beta-2Microglobulin Calibration VerificationMaterial (CVM) is for in vitrodiagnostic use in the verification ofcalibration of the IMMULITE Beta-2Microglobulin assay on the IMMULITE2000 systems. | The IMMULITE® 2000 Intact PTHCalibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Intact PTH assay on theIMMULITE 2000 systems |
| Storage | <-20°C | Same |
| Form | Lyophilized | Same |
| Stability | Stable unopened until theexpiration date | Same |
| Levels | 4 | Same |
| Matrix | Buffered bovine/protein withpreservatives | Same |
| Use | Single Use Only | Same |
| DIFFERENCES | ||
| Candidate DeviceIMMULITE 2000 Beta-2Microglobulin CVM | Predicate DeviceIMMULITE 2000 Intact PTH CVM | |
| Analyte | Beta-2 Microglobulin | Intact PTH |
7. Non-Clinical Performance Testing
Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.
Stability Summary:
The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 Beta-2 Microglobulin Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Verification Materials are stable up to 9 years when
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stored at -20°C prior to opening. Real time stability testing will continue for lots 011 and 012 until 119 month time point.
Open Component stability studies presents results that support 8 hours of stability at ambient or room temperature (15-25°C) after opening.
Stability Protocol Summary:
The CVM study protocols are run as part of the calibrator stability testing. The stability calibrators/CVMs are run in duplicate (as a minimum) at the time points shown in Table 2a-c, and the dose value is determined from the reference calibrator curve.
| Table 2a: Stability Protocol Summary - LBMCVM Lot 010 | ||||
|---|---|---|---|---|
| CVM Level | Time-Points (Months) | |||
| LBMCVM1 | Day 0 | 92 | 110 | 119 |
| LBMCVM2 | Day 0 | 92 | 110 | 119 |
| LBMCVM3 | Day 0 | 92 | 110 | 119 |
| LBMCVM4 | Day 0 | 92 | 110 | 119 |
Toble 20: Stability Protocol Summery . I RMCVM I ot 010
Table 2b: Stability Protocol Summary - LBMCVM Lot 011
| CVM Level | Time-Points (Months) | |||
|---|---|---|---|---|
| LBMCVM1 | Day 0 | 36 | 48 | 72 |
| LBMCVM2 | Day 0 | 36 | 48 | 72 |
| LBMCVM3 | Day 0 | 36 | 48 | 72 |
| LBMCVM4 | Day 0 | 36 | 48 | 72 |
Table 2c: Stability Protocol Summary - LBMCVM Lot 012
| CVM Level | Time-Points (Months) | |||
|---|---|---|---|---|
| LBMCVM1 | Day 0 | 18 | 36 | 42 |
| LBMCVM2 | Day 0 | 18 | 36 | 42 |
| LBMCVM3 | Day 0 | 18 | 36 | 42 |
| LBMCVM4 | Day 0 | 18 | 36 | 42 |
For Open Component testing, the results were determined from a 2-point adjustment. Using IMMULITE 2000 Beta-2 Microglobulin (L2KBM) kit lot 247, CVM lot 012 was tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.
Stability Acceptance Criteria Summary:
The Acceptance Criteria for the Beta-2 Microglobulin Calibration 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 and ±20% for levels 3 and 4. Part 2 review limits criteria which require dose value of the controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±15% of assigned dose for CVM level 2 and ±20% for levels 3 and 4, then additional data review is conducted using part 2 criteria.
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Traceability:
The IMMULITE 2000 Beta-2 Microglobulin CVMs are traceable to an internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.
Value Assignment:
The IMMULITE 2000 Beta-2 Microglobulin CVMs are 4 level materials which are a subset of 7 level Beta-2 Microglobulin calibrators are not commercialized but are used internally during manufacture and release testing of Beta-2 Microglobulin reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned reference calibrators. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each 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. Three levels of commercially available controls and 40 patient samples (20 spiked and diluted urine samples, 10 neat urine samples and 10 diluted serum samples) were used to validate calibrator/CVM value assignments.
Expected Values/Target Values/Reference Range:
Each CVM level was tested for a total of 15 replicates; 5 runs and 3 replicates per run, 3 different reagent kit lots and 5 IMMULITE 2000 systems. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The target values are provided in the IMMULITE® 2000 CVM Calibration Material lotspecific value card. The expected assay range is 4 to 500 ng/mL. The target values in Table 3 can be considered as guidelines.
| Analyte target | CVM Level | *Target | Standard | Guideline ±2SD Range | |
|---|---|---|---|---|---|
| levels | Mean | Deviation | (ng/mL) | ||
| (ng/mL | (SD) | ||||
| LBMCVM1 | 0.00 | 0.00 | <4.0 | ||
| LBMCVM2 | 27.8 | 2.8 | 22.2 | 33.4 | |
| LBMCVM3 | 225 | 23.5 | 178 | 272 | |
| LBMCVM4 | 504 | 50.5 | 403 | ୧୦૨ | |
| Assay Range | 4 to 500 ng/mL |
| Table 3: Analyte Target Range Values | ||
|---|---|---|
| J |
Note * When CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software. If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.
Each laboratory should establish their limits for acceptability based on methodology, clinical significance and medical decision levels of the test analyte. The representative, total precision tabulated in the respective assay instructions for use may be considered as one factor when establishing local, acceptable ranges. The values provided above may be considered as guidelines. Value assignment is lot specific.
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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 Beta-2 Microglobulin Calibration Material is substantially equivalent to the predicate device intended for similar use. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Beta-2 Microglobulin 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. SubmitterMailing Address: | Siemens Healthcare Diagnostics Inc.5210 Pacific Concourse DriveLos Angeles, CA 90045 |
|---|---|
| Contact Person:Phone Number:Fax Number:E-mail Address:Date Prepared: | Donna VelasquezRegulatory Technical Specialist(310) 645-8200 x7403(310) 645-9999donna.velasquez@siemens.comOctober 28th, 2014 |
| 2. Device NameProprietary Name: | IMMULITE® 2000 High Sensitivity CRP Calibration VerificationMaterial |
| Measurand: | Quality Control materials for IMMULITE® 2000 High SensitivityCRP assay |
| Type of Test:Regulation Section:Classification:Products Code: | Calibration Verification Material (CVM) for IMMULITE® 2000High Sensitivity CRP assay21 CFR 862.1660, Quality Control MaterialClass I ReservedJJX - Single (Specified) Analyte Controls (Assayed andUnassayed) |
| Panel: | Clinical Chemistry (75) |
| 3. Predicate Device NamePredicate 510(k) No: | IMMULITE 2000 Homocysteine Calibration Verification Material(CVM)K133128 |
| 4. Device Description: | The IMMULITE® 2000 High Sensitivity CRP CalibrationVerification Material (CVM) contains one set of four vials, 2mLeach. CVM1 contains a bovine protein/buffer with 0.098% sodiumazide and preservative. CVM2, CVM3, and CVM4 contain variouslevels of human CRP in a bovine protein/buffer with 0.098%sodium azide and preservative. |
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| 5. Intended Use:Indication for Use: | See Indications for Use Statement belowThe IMMULITE® 2000 High Sensitivity CRP CalibrationVerification Material (CVM) is for in vitro diagnostic use in theverification of calibration of the IMMULITE High SensitivityCRP assay on the IMMULITE 2000 systems |
|---|---|
| Special Conditions forUse Statement(s):Special InstrumentRequirements:6. Technological Characteristics | For prescription use onlyIMMULITE® 2000 Systems |
| and Substantial EquivalenceComparison with Predicate: | A comparison of the device features, intended use, and otherinformation demonstrates that the IMMULITE® 2000 HighSensitivity CRP Calibration Verification Material (CVM) issubstantially equivalent to the predicate device as summarized inTable 1. |
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 High SensitivityCRP CVM | Predicate DeviceIMMULITE 2000 HomocysteineCVM | |
| IntendedUse | The IMMULITE® 2000 High SensitivityCRP Calibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE High Sensitivity CRP assayon the IMMULITE 2000 systems | The IMMULITE® 2000Homocysteine CalibrationVerification Material (CVM) is for invitro diagnostic use in the verificationof calibration of the IMMULITEHomocysteine assay on theIMMULITE 2000 systems |
| Form | Liquid | Same |
| Levels | 4 | Same |
| Stability | Stable unopened until the expiration date | Same |
| Matrix | Bovine protein/buffer matrix | Same |
| Use | Single Use Only | Same |
| Table 1: Substantial Equivalence Comparison | |
|---|---|
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 High SensitivityCRP CVM | Predicate DeviceIMMULITE 2000 HomocysteineCVM | |
| Storage | 2-8°C | ≤20°C |
| Analyte | High Sensitivity CRP | Homocysteine |
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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 intend use. The following tests were performed on the candidate device.
Stability Summary:
The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 High Sensitivity CRP Calibration Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Materials are stable up to 11 months when stored at 2-8°C prior to opening, and for 8 hours at ambient or room temperature (15-25°C) after 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) at the time points shown in Table 2a-c and the dose value determined from the reference calibrator curve.
| CVM Level | Time-Points (Months) | |||
|---|---|---|---|---|
| LCRPCVM1 | Day 0 | 12 | 18 | 23 |
| LCRPCVM2 | Day 0 | 12 | 18 | 23 |
| LCRPCVM3 | Day 0 | 12 | 18 | 23 |
| LCRPCVM4 | Day 0 | 12 | 18 | 23 |
Table 2a: Stability Protocol Summary - LCRPCVM Lot 025
Table 2b: Stability Protocol Summary - LCRPCVM Lot 026
| CVM Level | Time-Points (Months) | ||||
|---|---|---|---|---|---|
| LCRPCVM1 | Day 0 | 7 | 8 | 12 | |
| LCRPCVM2 | Day 0 | 7 | 8 | 12 | |
| LCRPCVM3 | Day 0 | 7 | 8 | 12 | |
| LCRPCVM4 | Day 0 | 7 | 8 | 12 |
Table 2c: Stability Protocol Summary - LCRPCVM Lot 090
| CVM Level | Time-Points (Months) | |||
|---|---|---|---|---|
| LCRPCVM1 | Day 0 | 4 | 6 | 11 |
| LCRPCVM2 | Day 0 | 4 | 6 | 11 |
| LCRPCVM3 | Day 0 | 4 | 6 | 11 |
| LCRPCVM4 | Day 0 | 4 | 6 | 11 |
Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE 2000 High Sensitivity CRP Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability CVMs to fall between ±20% of the assigned dose for CVM level 2, ±6% of the assigned dose for level 3 and ±10% of assigned dose for CVM level 4. Part 2 review limits criteria which require dose value of the controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose
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range of ±20% of the assigned dose for CVM level 2, ±6% of the assigned dose for level 3 and ±10% of assigned dose for CVM level 4 then additional data review is conducted using part 2 criteria.
Traceability:
The IMMULITE 2000 High Sensitivity CRP CVMs are traceable to WHO 1* IS 85/506 and CRM 470. The CVMs are manufactured using qualified materials and measurement procedures.
Value Assignment:
The IMMULITE 2000 High Sensitivity CRP CVMs are 4 level materials which are a subset of 10 level High Sensitivity CRP calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of High Sensitivity CRP reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned reference calibrators. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The controls must fall within their target ranges. Three levels of commercially available controls and 28 samples (21 normal samples and 7 spiked samples) were used to validate calibrator/CVM value assignments.
Expected Values/Target Values/Reference Range:
The CVMs are manufactured using qualified materials and measurement procedures. The High Sensitivity CRP CVMs were tested on 15 replicates in total comprised of 5 runs and 3 replicates per run on 4 IMMULITE 2000 systems and 3 different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). *
The expected assay range is 0.2 to 100 mg/L. The target values in Table 3 can be considered as guidelines.
| Analyte targetlevels | CVM Level | **TargetMean(mg/L) | StandardDeviation(SD) | Guideline ±2SD Range(mg/L) |
|---|---|---|---|---|
| LCRPCVM1 | 0.00 | - | ≤0.20 | |
| LCRPCVM2 | 1.27 | 0.125 | 1.52 | |
| LCRPCVM3 | 11.1 | 0.71 | 12.5 | |
| LCRPCVM4* | 157 | - | - | |
| 65% LCRPCVM4 +35% LCRPCVM1 | 102 | 7.575 | 117 |
Table 3: Analyte Target Range Levels
Assay Kange | 0.2 to 100 mg/L
Note* CVM4 requires dilution to ensure that the target value is within the +10% of the top of the reportable range of the assay.
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- ** When CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software. If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.
Each laboratory should establish their limits for acceptability based on methodology, clinical significance and medical decision levels of the test analyte. The representative, total precision tabulated in the respective assay instructions for use may be considered as one factor when establishing local, acceptable ranges. The values provided above may be considered as guidelines. Value assignment is lot specific.
Standard/Guidance Documents Referenced:
- CEN 13640 Stability Testing of In Vitro Diagnostic Reagents ●
- Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic Calibrators ●
- Guidance for Industry and FDA Staff Assayed and Unassayed Quality Control Material ●
Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10
8. Conclusion:
The IMMULITE® 2000 High Sensitivity CRP Calibration Material is substantially equivalent to the predicate device intended for similar use. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 High Sensitivity CRP Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.
§ 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.