(35 days)
The IMMULITE® Albumin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Albumin assay on the IMMULITE 2000 systems
The IMMULITE® Myoglobin Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Myoglobin assay on the IMMULITE 2000 systems
The Albumin Calibration Verification Material (CVM) contains one set of four vials each 2.0 mL after reconstitution. CVM1 contains bovine protein with preservatives. CVM2, CVM3 and CVM4 contain various levels of human albumin in a bovine protein matrix with preservatives. The CVMs are supplied in lyophilized form.
IMMULITE® 2000 Myoglobin Calibration Verification Material (CVM) contains one set of four vials each 2.0mL after reconstitution. CVM1 contains bovine serum with preservatives. CVM2, CVM3 and CVM4 contain various levels of human cardiac myoglobin in bovine serum with preservatives. The CVMs are supplied in lyophilized form.
The provided documents describe the performance testing for two medical devices: the IMMULITE® 2000 Albumin Calibration Verification Material (CVM) and the IMMULITE® 2000 Myoglobin Calibration Verification Material (CVM).
IMMULITE® 2000 Albumin Calibration Verification Material (CVM)
1. Table of Acceptance Criteria and Reported Device Performance
The device performance is reported as meeting the acceptance criteria, as stated in the stability summaries. The studies aimed to demonstrate that the CVM maintains optimal product performance within the established shelves life before and after reconstitution.
Table: Acceptance Criteria and Reported Device Performance for IMMULITE® 2000 Albumin CVM
| Test | CVM Level | Acceptance Criteria | Reported Device Performance |
|---|---|---|---|
| Shelf Life Stability | LHACVM1 | < 2.5 ug/mL (for assigned dose 0.00 ug/mL) | Stable up to 6 years at 2-8°C, meeting criteria. |
| LHACVM2 | ±10% difference from assigned dose (4.55-5.56 ug/mL for 5.05 ug/mL) | Stable up to 6 years at 2-8°C, meeting criteria. | |
| LHACVM3 | ±10% difference from assigned dose (18.6-22.8 ug/mL for 20.7 ug/mL) | Stable up to 6 years at 2-8°C, meeting criteria. | |
| LHACVM4 | ±15% difference from assigned dose (53.6-72.5 ug/mL for 63.0 ug/mL) | Stable up to 6 years at 2-8°C, meeting criteria. | |
| Open Vial Stability | LHACVM1 | ≤ 2.5 ug/mL (for assigned dose 0.00 ug/mL) | Stable up to 2 hours at 15-25°C, meeting criteria. |
| LHACVM2 | ±10% difference from initial time point dose (4.55-5.56 ug/mL for 5.05 ug/mL) | Stable up to 2 hours at 15-25°C, meeting criteria. | |
| LHACVM3 | ±10% difference from initial time point dose (18.6-22.8 ug/mL for 20.7 ug/mL) | Stable up to 2 hours at 15-25°C, meeting criteria. | |
| LHACVM4 | ±15% difference from initial time point dose (53.6-72.5 ug/mL for 63.0 ug/mL) | Stable up to 2 hours at 15-25°C, meeting criteria. |
2. Sample size used for the test set and data provenance
- Test Set Sample Size: For both Shelf Life Stability and Open Vial Stability, CVMs and reference CVMs were run in duplicate (as a minimum) at specified time points.
- Value Assignment & Reference Range: Each CVM level was tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, using 9 IMMULITE 2000 systems and 3 different reagent kit lots.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the context of a 510(k) submission for a diagnostic product, it is most likely prospective testing conducted in-house by Siemens Healthcare Diagnostics.
3. Number of experts used to establish the ground truth for the test set and their qualifications
Not applicable. This device is a calibration verification material, not an AI/diagnostic algorithm that interprets patient data. The "ground truth" here refers to the assigned dose values and acceptable ranges based on manufacturing protocols and established analytical standards for the calibrators.
4. Adjudication method for the test set
Not applicable. This device is a calibration verification material.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done
Not applicable. This device is a calibration verification material, not an AI diagnostic intended for human reader interpretation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in the sense that the performance testing described measures the analytical performance of the CVM on the IMMULITE 2000 systems as an "algorithm only" (or rather, "device only") measurement of its stability and value assignment, without human interpretation as part of the primary outcome. The CVM's ability to verify calibration of the assay is its intended function.
7. The type of ground truth used
The ground truth for the CVMs is based on assigned dose values traceable to an internal material. For value assignment, the calibrators (and thus CVMs) are value-assigned using assigned reference calibrators prepared using Albumin antigen stock, traceable to an internal material. Validation of these value assignments involved commercially available controls and 23 urine samples.
8. The sample size for the training set
Not applicable for a CVM calibration material. The "training" here relates to the establishment of the assay's calibration curve, not an AI model.
9. How the ground truth for the training set was established
Not applicable for a CVM calibrator material. The "ground truth" for the calibrators and CVMs is established through gravimetric preparation and traceability to an internal standard as detailed in section 7.3 and 7.4.
IMMULITE® 2000 Myoglobin Calibration Verification Material (CVM)
1. Table of Acceptance Criteria and Reported Device Performance
The device performance is reported as meeting the acceptance criteria, as stated in the stability summaries. The studies aimed to demonstrate that the CVM maintains optimal product performance within the established shelves life before and after reconstitution.
Table: Acceptance Criteria and Reported Device Performance for IMMULITE® 2000 Myoglobin CVM
| Test | CVM Level | Acceptance Criteria | Reported Device Performance |
|---|---|---|---|
| Shelf Life Stability | LMYCVM1 | ≤2.0 ng/mL (for assigned dose 0.00 ng/mL) | Stable up to 7 years at -20°C, meeting criteria. |
| LMYCVM2 | ±10% difference from assigned dose (23.9-29.3 ng/mL for 26.6 ng/mL) | Stable up to 7 years at -20°C, meeting criteria. | |
| LMYCVM3 | ±10% difference from assigned dose (104-128 ng/mL for 116 ng/mL) | Stable up to 7 years at -20°C, meeting criteria. | |
| LMYCVM4 | ±10% difference from assigned dose (945-1155 ng/mL for 1050 ng/mL) | Stable up to 7 years at -20°C, meeting criteria. | |
| Open Vial Stability | LMYCVM1 | ≤ 2.0 ng/mL (for assigned dose 0.00 ng/mL) | Stable up to 8 hours after reconstitution, meeting criteria. |
| LMYCVM2 | ±10% difference from initial time point dose (23.9-29.3 ng/mL for 26.6 ng/mL) | Stable up to 8 hours after reconstitution, meeting criteria. | |
| LMYCVM3 | ±10% difference from initial time point dose (104-128 ng/mL for 116 ng/mL) | Stable up to 8 hours after reconstitution, meeting criteria. | |
| LMYCVM4 | ±10% difference from initial time point dose (945-1155 ng/mL for 1050 ng/mL) | Stable up to 8 hours after reconstitution, meeting criteria. |
2. Sample size used for the test set and data provenance
- Test Set Sample Size: For both Shelf Life Stability and Open Vial Stability, CVMs and reference CVMs were run in duplicate (as a minimum) at specified time points.
- Value Assignment & Reference Range: Each CVM level was tested on 15 replicates in total, comprised of 5 runs, 3 replicates per run, using 3 IMMULITE 2000 systems and 4 different reagent kit lots.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the context of a 510(k) submission for a diagnostic product, it is most likely prospective testing conducted in-house by Siemens Healthcare Diagnostics.
3. Number of experts used to establish the ground truth for the test set and their qualifications
Not applicable. This device is a calibration verification material, not an AI/diagnostic algorithm that interprets patient data.
4. Adjudication method for the test set
Not applicable. This device is a calibration verification material.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done
Not applicable. This device is a calibration verification material, not an AI diagnostic intended for human reader interpretation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in the sense that the performance testing described measures the analytical performance of the CVM on the IMMULITE 2000 systems as an "algorithm only" (or rather, "device only") measurement of its stability and value assignment, without human interpretation as part of the primary outcome. The CVM's ability to verify calibration of the assay is its intended function.
7. The type of ground truth used
The ground truth for the CVMs is based on assigned dose values traceable to an internal standard. For value assignment, the calibrators (and thus CVMs) are value-assigned using assigned reference calibrators prepared using Myoglobin antigen stock, traceable to an internal standard. Validation of these value assignments involved three levels of commercially available controls and 30 samples (25 spiked samples and 5 normal samples).
8. The sample size for the training set
Not applicable for a CVM calibration material. The "training" here relates to the establishment of the assay's calibration curve, not an AI model.
9. How the ground truth for the training set was established
Not applicable for a CVM calibrator material. The "ground truth" for the calibrators and CVMs is established through gravimetric preparation and traceability to an internal standard as detailed in section 7.3 and 7.4.
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, formed by three overlapping profiles of human faces.
January 14, 2015
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
SIEMENS HEALTHCARE DIAGNOSTICS INC. SARA KASTRUP REGULATORY CLINICAL AFFAIRS SPECIALIST 511 BENEDICT AVENUE TARRYTOWN NY 10591
Re: K143504
Trade/Device Name: IMMULITE® 2000 Albumin Calibration Verification Material, IMMULITE® 2000 Myoglobin 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: December 9, 2014 Received: December 10, 2014
Dear Ms. Sara Kastrup:
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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{1}------------------------------------------------
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/ResourcesforYou/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,
Stayce Beck -S
For : 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}------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known)
K143504
Device Name
IMMULITE® 2000 Albumin Calibration Verification Material (CVM) IMMULITE® 2000 Myoglobin Calibration Verification Material (CVM)
Indications for Use (Describe)
The IMMULITE® Albumin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Albumin assay on the IMMULITE 2000 systems
The IMMULITE® Myoglobin Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Myoglobin 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)
Form Approved: OMB No. 0910-0120
Expiration Date: January 31, 2017
See PRA Statement below.
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}------------------------------------------------
Section 006: 510(k) Summary
510(k) Summary
Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.
The assigned 510(k) Number: _
-
- Submitter Mailing Address:
Contact Person:
- Submitter Mailing Address:
Phone Number: Fax Number: E-mail Address: Date Prepared:
-
- Device Name Proprietary Name: Measurand:
Type of Test:
- Device Name Proprietary Name: Measurand:
Regulation Section: Classification: Products Code: Panel:
- Predicate Device Name
Predicate 510(k) No:
- Device Description:
Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591
Sara Kastrup Regulatory Clinical Affairs Specialist (914)-524-2317 (914)-524-2101 sara.kastrup@siemens.com December 9th, 2014
IMMULITE® 2000 Albumin Calibration Verification Material Quality Control materials for IMMULITE® 2000 Albumin assay Calibration Verification Material (CVM) for IMMULITE® 2000 Albumin assay
21 CFR 862.1660, Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)
IMMULITE® 2000 SHBG Calibration Verification Material (CVM)
The Albumin Calibration Verification Material (CVM) contains one set of four vials each 2.0 mL after reconstitution. CVM1 contains bovine protein with preservatives. CVM2, CVM3 and CVM4 contain various levels of human albumin in a bovine protein matrix with preservatives. The CVMs are supplied in lyophilized form.
{4}------------------------------------------------
| 5. Intended Use:Indication for Use: | See Indications for Use Statement below:The IMMULITE® Albumin Calibration Verification Material (CVM)is for in vitro diagnostic use in the verification of calibration of theIMMULITE Albumin assay on the IMMULITE 2000 systems. | ||||
|---|---|---|---|---|---|
| Special Conditions for | |||||
| Use Statement(s): | For prescription use only | ||||
| Warnings and Precautions: | Caution, potential biohazard | ||||
| Contains human source material. Each donation of human blood orblood component was tested by FDA-approved methods for thepresence of antibodies to human immunodeficiency virus type 1(HIV-1) and type 2 (HIV-2) as well as for hepatitis B surface antigen(HBsAg) and antibody to hepatitis C virus (HCV). The test resultswere negative (not repeatedly reactive.). No test offers completeassurance that these or other infectious agents are absent; thismaterial should be handled using good laboratory practices anduniversal precautions. | |||||
| Special Instrument | IMMULITE® 2000 Systems | ||||
| Requirements: | |||||
| 6. Technological Characteristicsand Substantial EquivalenceComparison with Predicate: | A comparison of the device features, intended use, and otherinformation demonstrates that the IMMULITE® 2000 AlbuminCalibration Verification Material (CVM) is substantially equivalent tothe predicate device as summarized in Table 1. |
{5}------------------------------------------------
| Table 1: Substantial Equivalence Comparison | |||
|---|---|---|---|
| -- | -- | ---------------------------------------------- | -- |
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 Albumin CVM | Predicate DeviceIMMULITE 2000 SHBG CVM | |
| IntendedUse | The IMMULITE® AlbuminCalibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Albumin assay on theIMMULITE 2000 systems. | The IMMULITE® SHBGCalibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration ofthe IMMULITE SHBG assay on theIMMULITE 2000 systems. |
| Form | Lyophilized | Same |
| Stability | Stable unopened until the expirationdate | Same |
| Levels | 4 | Same |
| Use | Single Use Only | Same |
| Storage | 2-8°C | Same |
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 Albumin CVM | Predicate DeviceIMMULITE 2000 SHBG CVM | |
| Analyte | Albumin | SHBG |
| Matrix | Bovine Protein with Preservatives | Buffered Bovine Protein with Preservatives |
{6}------------------------------------------------
7. Non-Clinical Performance Testing
Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intended use. The following tests were performed on the candidate device.
7.1 Shelf Life Stability Summary:
The stability study was conducted to validate real-time shelf life claim for the IMMULITE 2000 Albumin 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 Albumin Calibration Verification Materials are stable up to 6 years when stored at 2-8°C prior to reconstitution.
7.1.1 Shelf life Stability Protocol Summary:
The CVM study protocols are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) at the time points shown in Table 2 and the dose value determined from the reference calibrator curve.
| CVM level | Time-Points (months) | |||
|---|---|---|---|---|
| LHACVM1 | 0 | 54 | 72 | 84 |
| LHACVM2 | 0 | 54 | 72 | 84 |
| LHACVM3 | 0 | 54 | 72 | 84 |
| LHACVM4 | 0 | 54 | 72 | 84 |
Table 2: Shelf life Stability Time Points
7.1.2 Shelf Life Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE Albumin requires dose value of stability calibrator/CVM to fall between ±10% of assigned dose for CVM level 2 and 3, and ±15% for CVM level 4. The acceptance criterion is summarized in Table 3.
| Table 3 Acceptance criteria for stability of IMMULITE 2000 Albumin CVM | ||||
|---|---|---|---|---|
| CVM level | AssignedDose(ug/mL) | Guideline Criteria% difference toassigned dose | Acceptabledose range(ug/mL) | Review Limits |
|---|---|---|---|---|
| LHACVM1 | 0.00 | Not Applicable | < 2.5 | |
| LHACVM2 | ર : 05 | ±10% | 4.55-5.56 | Controls arewithin 2SD of |
| LHACVM3 | 20.7 | ±10% | 18.6-22.8 | target on eachcurve |
| LHACVM4 | 63.0 | +15% | 53.6-72.5 |
{7}------------------------------------------------
7.2 Open Vial Stability Summary:
The stability study was conducted to validate open component (in-use or open vial) shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 Albumin Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms after reconstitution.
The IMMULITE® 2000 Albumin Calibration Verification Materials are stable up to 2 hours at ambient or room temperature (15-25°C) after reconstitution.
7.2.1 Open Vial Stability Protocol Summary:
The stability CVMs and reference CVMs are run in duplicate (as a minimum) at the time points shown in Table 4 and the dose value determined from the on system 2-point adjustment.
| CVM level | Time-Points (hours) |
|---|---|
| LHACVM1 | 0 2 6 |
| LHACVM2 | 0 2 6 |
| LHACVM3 | 0 2 6 |
| LHACVM4 | 0 2 6 |
Table 4: Open Vial Stability Time Points
Using IMMULITE 2000 Albumin (L2KHA2) kit lot 236 Albumin CVM lot 092 was tested up to 6 hours at ambient or room temperature (15-25°C) conditions and compared to the determinations at time zero.
7.2.2 Open Vial Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE Albumin requires dose value of stability calibrator/CVM to fall between ±10% difference to the initial time point dose for CVM level 2 and 3, and ±15% to the initial time point does for CVM level 4. The acceptance criterion is summarized in Table 5.
{8}------------------------------------------------
| CVM level | AssignedDose(µg/mL) | Guideline Criteria% difference toinitial time point | Acceptabledose range(µg/mL) | Review Limits |
|---|---|---|---|---|
| LHACVM1 | 0.00 | Not Applicable | ≤ 2.5 | |
| LHACVM2 | 5.05 | ±10% | 4.55-5.56 | Controls arewithin 2SD oftarget on eachcurve |
| LHACVM3 | 20.7 | ±10% | 18.6-22.8 | |
| LHACVM4 | 63.0 | ±15% | 53.6-72.5 |
Table 5 Acceptance criteria for Open Vial stability of IMMULITE 2000 Albumin CVM
7.3 Traceability:
The IMMULITE Albumin CVMs are traceable to an internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.
7.4 Value Assignment:
IMMULITE Albumin CVMs are 4 level materials which are a subset of 7 level Albumin calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Albumin reagents and two point adjustors.
The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using Albumin antigen stock and are traceable to an internal material. Two levels of commercially available controls and 23 urine samples were used to validate calibrator/CVM value assignments.
The CVMs are manufactured using qualified materials and measurement procedures. The IMMULITE Albumin calibrators/CVMs were tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, 9 IMMULITE 2000 systems and 3 different reagent kit lots. The CVMs dose values are generated using the curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The controls must fall within their target ranges.
7.5 Expected Values/Reference Range:
Each CVM level was tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, 9 IMMULITE 2000 systems and 3 different reagent kit lots. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2
{9}------------------------------------------------
Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration Verification Material lot-specific package insert.
The expected assay range is 2.5-60 ug/mL. The target values in Table 6 can be considered as guidelines.
| Analyte | CVM Level | Target | Standard | Target Range | |
|---|---|---|---|---|---|
| target levels | Mean(ug/mL) | Deviation(SD) | (ug/mL) | ||
| LHACVM1 | 0.00 | 0.00 | 2.50 | ||
| LHACVM2 | 5.05 | 0.38 | 4.29 | 5.81 | |
| LHACVM3 | 20.7 | 2.05 | 16.6 | 24.8 | |
| LHACVM4 | 63.0 | 6.0 | 51.0 | 75.0 | |
| Assay Range | Up to 2.5-60μg/mL |
Table 6: 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
Conclusion: 8.
The IMMULITE® 2000 Albumin Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 SHBG Calibration Verification Material. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device,
{10}------------------------------------------------
Image /page/10/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 IMMULITE® 2000 Albumin Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.
{11}------------------------------------------------
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.511 Benedict AvenueTarrytown, NY 10591 |
|---|---|
| Contact Person: | Sara KastrupRegulatory Clinical Affairs Specialist |
| Phone Number: | (914)-524-2317 |
| Fax Number: | (914)-524-2101 |
| E-mail Address: | sara.kastrup@siemens.com |
| Date Prepared: | December 9th, 2014 |
| 2. Device NameProprietary Name: | IMMULITE® 2000 Myoglobin Calibration Verification Material |
| Measurand: | Quality Control material for IMMULITE® 2000 Myoglobin assay |
| Type of Test: | Calibration Verification Material (CVM) for IMMULITE® 2000Myoglobin 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 |
| Predicate 510(k) No: | (CVM) K140258 |
| 4. Device Description: | IMMULITE® 2000 Myoglobin Calibration Verification Material(CVM) contains one set of four vials each 2.0mL after reconstitution.CVM1 contains bovine serum with preservatives. CVM2, CVM3 andCVM4 contain various levels of human cardiac myoglobin in bovineserum with preservatives. The CVMs are supplied in lyophilizedform. |
| 5. Intended Use:Indication for Use: | See Indications for Use Statement belowThe IMMULITE® Myoglobin Calibration Verification Material(CVM) is for in vitro diagnostic use in the verification of calibrationof the IMMULITE Myoglobin assay on the IMMULITE 2000systems. |
{12}------------------------------------------------
| Special Conditions for | |
|---|---|
| Use Statement(s): | For prescription use only |
| Warnings and Precautions: | Caution, potential biohazard |
| Contains human source material. Each donation of human blood or | |
| blood component was tested by FDA-approved methods for the | |
| presence of antibodies to human immunodeficiency virus type 1 | |
| (HIV-1) and type 2 (HIV-2) as well as for hepatitis B surface antigen | |
| (HBsAg) and antibody to hepatitis C virus (HCV). The test results | |
| were negative (not repeatedly reactive.). No test offers complete | |
| assurance that these or other infectious agents are absent; this | |
| material should be handled using good laboratory practices and | |
| universal precautions. | |
| Special Instrument | |
| Requirements: | IMMULITE® 2000 Systems |
A comparison of the device features, intended use, and other 6. Technological information demonstrates that the the IMMULITE® Myoglobin Characteristics and Calibration Verification Material (CVM) is substantially equivalent to Substantial Equivalence Comparison with Predicate: the predicate device as summarized in Table 1.
{13}------------------------------------------------
Image /page/13/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 word is horizontally oriented and centered in the image.
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000Myoglobin CVM | Predicate DeviceIMMULITE 2000 Intact PTHCVM | |
| IntendedUse | The IMMULITE® Myoglobin CalibrationVerification Material (CVM) is for in vitrodiagnostic use in the verification ofcalibration of the IMMULITE Myoglobinassay on the IMMULITE 2000 systems | The IMMULITE® Intact PTHCalibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration ofthe IMMULITE Intact PTH assayon the IMMULITE 2000 systems |
| StorageStability | ≤-20°CStable unopened until the expiration date | Same |
| Levels | 4 | Same |
| Use | Single Use Only | Same |
| Matrix | Bovine Serum with preservatives | Same |
| Form | Lyophilized | Same |
Table 1: Substantial Equivalence Comparison
| DIFFERENCES | ||
|---|---|---|
| Candidate Device IMMULITE 2000Myoglobin CVM | Predicate DeviceIMMULITE 2000 Intact PTH CVM | |
| Analyte | Myoglobin | Intact PTH |
{14}------------------------------------------------
7. Non-Clinical Performance Testing
Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intended use. The following tests were performed on the candidate device.
7.1 Shelf life Stability Summary:
The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Myoglobin Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM before and after reconstitution.
The Myoglobin Calibration Verification Materials are stable up to 7 years when stored at -20°C.
7.1.1 Shelf life Stability Protocol Summary:
The CVM study protocols are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) at the time points shown in Table 2 and the dose value determined from the reference calibrator curve.
| CVM Level | Time-Points (months) | |||
|---|---|---|---|---|
| LMYCVM1 | 0 | 54 | 60 | 84 |
| LMYCVM2 | 0 | 54 | 60 | 84 |
| LMYCVM3 | 0 | 54 | 60 | 84 |
| LMYCVM4 | 0 | 54 | 60 | 84 |
Table 2: Shelf life Stability Time Points
7.1.2 Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE Myoglobin criteria requires dose value of stability calibrator/CVM to fall between ±10% of assigned dose for CVM level 2, 3, and 4.
The acceptance criterion is summarized in Table 3.
Table 3 Acceptance criteria for stability of IMMULITE 2000 Myoglobin CVM
| CVM level | Assigned Dose(ng/mL) | GuidelineCriteria% difference toassigned dose | Acceptable doserange (ng/mL) |
|---|---|---|---|
| LMYCVM1 | 0.00 | N/A | ≤2.0 |
| LMYCVM2 | 26.6 | ±10% | 23.9-29.3 |
| LMYCVM3 | 116 | ±10% | 104-128 |
| LMYCVM4 | 1050 | ±10% | 945-1155 |
{15}------------------------------------------------
7.2 Open Vial Stability Summary:
The stability study was conducted to validate the open component (in-use or open vial) for the IMMULITE 2000 Myoglobin Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms after reconstitution.
The Myoglobin Calibration Verification Materials are stable up to 8 hours after reconstitution.
7.2.1 Open Vial Stability Protocol Summary:
The stability CVMs and reference CVMs are run in duplicate (as a minimum) at the time points shown in Table 4 and the dose value determined from the on system 2-point adjustment.
Table 4: Open Vial Stability Time Points
| CVM Level | Time-Points (hours) | |||||
|---|---|---|---|---|---|---|
| LMYCVM1 | 0 | 2 | 4 | 6 | 8 | 9 |
| LMYCVM2 | 0 | 2 | 4 | 6 | 8 | 9 |
| LMYCVM3 | 0 | 2 | 4 | 6 | 8 | 9 |
| LMYCVM4 | 0 | 2 | 4 | 6 | 8 | 9 |
7.2.2 Open Vial Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE Myoglobin criteria requires dose value of stability calibrator/CVM to fall between ±10% difference to the initial time point dose for CVM level 2, 3, and 4.
The acceptance criterion is summarized in Table 5.
Table 5 Acceptance criteria for open vial stability of IMMULITE 2000 Myoglobin CVM
| CVM level | Assigned Dose (ng/mL) | Guideline Criteria % difference to initial time point | Acceptable dose range (ng/mL) |
|---|---|---|---|
| LMYCVM1 | 0.00 | N/A | ≤ 2.0 |
| LMYCVM2 | 26.6 | ±10% | 23.9-29.3 |
| LMYCVM3 | 116 | ±10% | 104-128 |
| LMYCVM4 | 1050 | ±10% | 945-1155 |
{16}------------------------------------------------
7.3 Traceability:
The IMMULITE Myoglobin CVMs are traceable to an internal standard. The CVMs are manufactured using qualified materials and measurement procedures.
7.4 Value Assignment:
The Myoglobin CVMs are 4 level materials which are a subset of 10 level Myoglobin calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Myoglobin reagents and two point adjustors.
The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using Myoglobin antigen stock and are traceable to an internal standard. Three levels of commercially available controls and 30 samples (25 spiked samples and 5 normal samples) were used to validate calibrator/CVM value assignments.
The calibrators/CVMs are manufactured using qualified materials and measurement procedures. The calibrators/CVMs were tested on 15 replicates in total, comprised of 5 runs, 3 replicates per run, 3 IMMULITE 2000 systems and 4 different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each 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.
7.5 Expected Values/Reference Range:
Each CVM level was on 15 replicates in total, comprised of 5 runs, 3 replicates per run, 3 IMMULITE 2000 systems and 4 different reagent kit lots. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 Myoglobin CVM Calibration Verification Material lot-specific package insert.
The expected assay range is up to 1000 ng/mL. The target values in Table 6 can be considered as guidelines.
{17}------------------------------------------------
Image /page/17/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.
| Analytetarget levels | CVM Level | TargetMean(ng/mL) | StandardDeviation(SD) | Target Range(ng/mL)n | |
|---|---|---|---|---|---|
| LMYCVM1 | 0.00 | - | 0.00 | ≤2.0 | |
| LMYCVM2 | 27.7 | 1.5 | 24.7 | 30.7 | |
| LMYCVM3 | 123 | 7.0 | 109 | 137 | |
| LMYCVM4 | 999 | 70 | 859 | 1139 | |
| Assay Range | Up to 1000 ng /mL |
| Table 6: Target Values | |||
|---|---|---|---|
| -------------------------- | -- | -- | -- |
Each laboratory should establish their limits for acceptability based on methodology, clinical significance and medical decision levels of the test analyte. The representative, total precision tabulated in the respective assay instructions for use may be considered as one factor when establishing local, acceptable ranges. The values provided above may be considered as guidelines. Value assignment is lot specific.
Standard/Guidance Documents Referenced:
- CEN 13640 Stability Testing of In Vitro Diagnostic Reagents ●
- Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic . Calibrators
- Guidance for Industry and FDA Staff Assayed and Unassayed Quality Control ● Material
Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10
8. Conclusion:
The IMMULITE® 2000 Myoglobin Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 Intact PTH Calibration Verification Material. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Myoglobin 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.