(28 days)
Not Found
No
The device is a calibration verification material, a physical substance used to verify the calibration of an assay on a specific instrument. The description focuses on the composition, stability, and value assignment of the material, with no mention of AI or ML algorithms for data processing or interpretation.
No
The device is described as a "Calibration Verification Material" (CVM) for in vitro diagnostic use, meaning it's used to verify the calibration of assays on diagnostic systems, not to directly treat a patient.
No
This device is described as "Calibration Material" and "Calibration Verification Material (CVM)" for in vitro diagnostic use in the verification of calibration of assays. It is used to ensure the accuracy of other diagnostic devices, rather than performing a diagnostic function itself.
No
The device description clearly states that the device is a material (vials containing solutions) used for calibration verification, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states:
- "IMMULITE® 2000 Beta-2 Microglobulin Calibration Material (CVM) is for in vitro diagnostic use..."
- "IMMULITE® 2000 High Sensitivity CRP Calibration Material (CVM) is for in vitro diagnostic use..."
This directly indicates that the device is intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
JJX
Device Description
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
For prescription use only
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
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: Beta-2 Microglobulin CVM
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 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: Beta-2 Microglobulin CVM
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 (Time-Points (Months): Day 0, 92, 110, 119 for CVM Levels 1-4)
Table 2b: Stability Protocol Summary - LBMCVM Lot 011 (Time-Points (Months): Day 0, 36, 48, 72 for CVM Levels 1-4)
Table 2c: Stability Protocol Summary - LBMCVM Lot 012 (Time-Points (Months): Day 0, 18, 36, 42 for CVM Levels 1-4)
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.
Value Assignment: Beta-2 Microglobulin CVM
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: Beta-2 Microglobulin CVM
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 lot-specific value card. The expected assay range is 4 to 500 ng/mL. The target values in Table 3 can be considered as guidelines.
Stability Summary: High Sensitivity CRP CVM
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: High Sensitivity CRP CVM
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.
Table 2a: Stability Protocol Summary - LCRPCVM Lot 025 (Time-Points (Months): Day 0, 12, 18, 23 for CVM Levels 1-4)
Table 2b: Stability Protocol Summary - LCRPCVM Lot 026 (Time-Points (Months): Day 0, 7, 8, 12 for CVM Levels 1-4)
Table 2c: Stability Protocol Summary - LCRPCVM Lot 090 (Time-Points (Months): Day 0, 4, 6, 11 for CVM Levels 1-4)
Value Assignment: High Sensitivity CRP CVM
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: High Sensitivity CRP CVM
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.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Stability Acceptance Criteria Summary: Beta-2 Microglobulin CVM
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.
Stability Acceptance Criteria Summary: High Sensitivity CRP CVM
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 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.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
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
1
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
2
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."
3
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."
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: ____________________
| 1. Submitter | |
|---|---|
| Mailing Address: | Siemens Healthcare Diagnostics Inc. |
| 5210 Pacific Concourse Drive | |
| Los Angeles, CA 90045 | |
| Contact Person: | Donna Velasquez |
| Regulatory 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 Verification |
| Material | |
| Measurand: | Quality Control materials for IMMULITE® 2000 Beta-2 |
| Microglobulin assay | |
| Type of Test: | Calibration Verification Material (CVM) for IMMULITE® 2000 |
| Beta-2 Microglobulin 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 Intact PTH Calibration Verification Material |
| (CVM) | |
| Predicate 510(k) No: | K140258 |
| 4. Device Description: | 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. | |
| 5. Intended Use: | |
| Indication for Use: | See Indications for Use Statement below |
| The IMMULITE® 2000 Beta-2 Microglobulin Calibration | |
| Verification 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 | |
| Special Conditions for | |
| Use Statement(s): | For prescription use only |
5
Image /page/5/Picture/0 description: The image shows the word "SIEMENS" in a bold, sans-serif font. The color of the text is a bright teal. The letters are evenly spaced and the word is horizontally oriented. The background is plain white.
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 Device | ||
| IMMULITE 2000 Beta-2 | ||
| Microglobulin CVM | Predicate Device | |
| IMMULITE 2000 Intact PTH | ||
| CVM | ||
| Intended | ||
| Use | The IMMULITE® 2000 Beta-2 | |
| Microglobulin Calibration Verification | ||
| 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. | The IMMULITE® 2000 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 | ||
| Storage | 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.
8
Image /page/8/Picture/0 description: The image contains the word "SIEMENS" in all capital letters. The text is displayed in a bold, sans-serif font. The color of the text is a bright teal.
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.
9
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 Drive
Los Angeles, CA 90045 |
|--------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person:
Phone Number:
Fax Number:
E-mail Address:
Date Prepared: | Donna Velasquez
Regulatory Technical Specialist
(310) 645-8200 x7403
(310) 645-9999
donna.velasquez@siemens.com
October 28th, 2014 |
| 2. Device Name
Proprietary Name: | IMMULITE® 2000 High Sensitivity CRP Calibration Verification
Material |
| Measurand: | Quality Control materials for IMMULITE® 2000 High Sensitivity
CRP assay |
| Type of Test:
Regulation Section:
Classification:
Products Code: | Calibration Verification Material (CVM) for IMMULITE® 2000
High Sensitivity CRP assay
21 CFR 862.1660, Quality Control Material
Class I Reserved
JJX - Single (Specified) Analyte Controls (Assayed and
Unassayed) |
| Panel: | Clinical Chemistry (75) |
| 3. Predicate Device Name
Predicate 510(k) No: | IMMULITE 2000 Homocysteine Calibration Verification Material
(CVM)
K133128 |
| 4. Device Description: | 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. |
10
| 5. Intended Use:
Indication for Use: | See Indications for Use Statement below
The IMMULITE® 2000 High Sensitivity CRP Calibration
Verification 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 |
|------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Special Conditions for
Use Statement(s):
Special Instrument
Requirements:
6. Technological Characteristics | For prescription use only
IMMULITE® 2000 Systems |
| and Substantial Equivalence
Comparison with Predicate: | A comparison of the device features, intended use, and other
information demonstrates that the IMMULITE® 2000 High
Sensitivity CRP Calibration Verification Material (CVM) is
substantially equivalent to the predicate device as summarized in
Table 1. |
| SIMILARITIES | ||
|---|---|---|
| Candidate Device | ||
| IMMULITE 2000 High Sensitivity | ||
| CRP CVM | Predicate Device | |
| IMMULITE 2000 Homocysteine | ||
| CVM | ||
| Intended | ||
| Use | The IMMULITE® 2000 High Sensitivity | |
| CRP Calibration Verification 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 | |
| Homocysteine Calibration | ||
| Verification Material (CVM) is for in | ||
| vitro diagnostic use in the verification | ||
| of calibration of the IMMULITE | ||
| Homocysteine assay on the | ||
| IMMULITE 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 Device | ||
| IMMULITE 2000 High Sensitivity | ||
| CRP CVM | Predicate Device | |
| IMMULITE 2000 Homocysteine | ||
| CVM | ||
| Storage | 2-8°C | ≤20°C |
| Analyte | High Sensitivity CRP | Homocysteine |
11
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
12
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 target
levels | CVM Level | *Target
Mean
(mg/L) | Standard
Deviation
(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.
13
Image /page/13/Picture/0 description: The image shows the word "SIEMENS" in a teal, sans-serif font. The letters are bold and evenly spaced. The background is plain white, which makes the text stand out.
- ** 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 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.