(32 days)
The IMMULITE® CEA Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE CEA assay on the IMMULITE 2000 systems.
The CEA Calibration Verification Material (CVM) contains one set of four vials each 1.0mL after reconstitution. CVM1 contains lyophilized processed human serum with preservatives. CVM2, CVM3 and CVM4 contain various levels of human CEA in a lyophilized processed human serum matrix with preservatives.
This document describes the IMMULITE® 2000 CEA Calibration Verification Material (CVM), an in vitro diagnostic device used to verify the calibration of the IMMULITE CEA assay on IMMULITE 2000 systems. The provided text, however, does not align with the standard format for reporting AI/ML device studies as it describes a calibration verification material, not an AI-based device. Therefore, many of the requested fields are not applicable.
Here's the information extracted and adapted where possible:
1. A table of acceptance criteria and the reported device performance
| Acceptance Criteria (Stability) | Reported Device Performance (Stability) |
|---|---|
| Real-time Shelf-Life: Sample dose falls within ±10% difference for CVM levels 2 and 3, and ±15% for CVM level 4, compared to dose at time point zero. (If criteria fail, stability assessed by analyte drift analysis as described in protocol summary) | Real-time Shelf-Life: Stable up to 6 years when stored at -20°C prior to opening. The study protocols for three lots (006, 007, 090) included time points up to 108 months, 84 months, and 6 months respectively for different CVM levels. The conclusion states the materials are stable up to 6 years at -20°C. Specific performance data with results against acceptance criteria are not presented in a table. |
| Open Component (in-use) Stability: Sample dose falls within ±10% difference for CVM levels 2 and 3, and ±15% for CVM level 4, compared to dose at time point zero. (If criteria fail, stability assessed by analyte drift analysis as described in protocol summary) | Open Component Stability: Stable for 8 hours at ambient or room temperature (15-25°C) after reconstitution. CVM lot 090 was tested at 2-hourly intervals for up to 9 hours to compare against time zero. Specific performance data with results against acceptance criteria are not presented in a table. |
2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Test Set Sample Size: For stability testing, three lots of CVMs (Lot 006, 007, and 090) were used. For value assignment and expected values, each CVM level was tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, using 9 IMMULITE 2000 systems and 5 different reagent kit lots.
- Data Provenance: Not specified, but generally, such studies are conducted at the manufacturer's facilities. The document does not indicate country of origin or whether the data was retrospective or prospective, though stability studies are inherently prospective.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
- Not applicable. This device is a calibration verification material for an in vitro diagnostic assay, not an AI/ML device relying on expert interpretation for ground truth. The "ground truth" for CVMs is based on internal reference standards and gravimetric preparations.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Not applicable. This is not an AI/ML device requiring human adjudication of results.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- Not applicable. This is a calibration verification material, not an AI-assisted diagnostic tool for human readers.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
- Not applicable. This is a physical control material.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- Ground Truth for CVMs: The IMMULITE CEA CVMs are traceable to an internal standard. The assigned reference calibrators are prepared using CEA antigen stock and are traceable to an internal standard which has been gravimetrically prepared.
8. The sample size for the training set
- Not applicable. This is not an AI/ML device with a training set. The "IMMULITE CEA kit lot 290" and "CEA CVM lot 090" mentioned in the stability protocol are parts of the experimental setup for assessing the CVM's performance, not a training set for an algorithm.
9. How the ground truth for the training set was established
- Not applicable. This is not an AI/ML device with a training set.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 9, 2015
Siemens Healthcare Diagnostics Inc. c/o Ms. Asha Gartland Technical Regulatory Affairs Specialist 511 Benedict Avenue Tarrytown, NY 10591
Re: K143639
Trade/Device Name: IMMULITE® 2000 CEA Calibration Verification Material Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (Assayed and Unassayed) Regulatory Class: Class I, Reserved Product Code: JJX Dated: December 19, 2014 Received: December 22, 2014
Dear Ms. Gartland,
This letter corrects our substantially equivalent letter of January 23, 2015.
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. Iisting 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
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CFR Part 807); labeling (21 CFR Part 801); 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.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of 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.
Leonthena R. Carrington -S
Leonthena Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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| Form Approved: OMB No. 0910-0120 |
|---|
| Expiration Date: January 31, 2017 |
| See PRA Statement below. |
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Indications for Use
| 510(k) Number (if known) | K143639 |
|---|---|
| Device Name | IMMULITE® 2000 CEA Calibration Verification Material |
| Indications for Use (Describe) | The IMMULITE® CEA Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE CEA 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.
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| FORM FDA 3881 (8/14) | Page 1 of 1 |
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PSC Publishing Services (301) 443-6740 EF
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SIEME
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: K143639
| 1. SubmitterMailing Address: | Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591 |
|---|---|
| Contact Person: | Asha GartlandTechnical Regulatory Affairs Specialist |
| Phone Number: | (914)-524-3257 |
| Fax Number: | (914)-524-2101 |
| E-mail Address: | asha.gartland@siemens.com |
| Date Prepared: | January 20th, 2015 |
-
- 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:
IMMULITE® 2000 CEA Calibration Verification Material Quality Control materials for IMMULITE® 2000 CEA assay Calibration Verification Material (CVM) for IMMULITE® 2000 CEA assay
21 CFR 862.1660, Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Immunology (82)
IMMULITE® 2000 DHEA-SO4 Calibration Verification Material (CVM) K140258
The CEA Calibration Verification Material (CVM) contains one set of four vials each 1.0mL after reconstitution. CVM1 contains lyophilized processed human serum with preservatives. CVM2, CVM3 and CVM4 contain various levels of human CEA in a lyophilized processed human serum matrix with preservatives.
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-
- Intended Use: Indication for Use:
Special Conditions for Use Statement(s): Special Instrument Requirements:
- Intended Use: Indication for Use:
- Technological Characteristics and Substantial Equivalence Comparison with Predicate:
See Indications for Use Statement below: The IMMULITE® CEA Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE CEA assay on the IMMULITE 2000 systems.
For prescription use only
IMMULITE® 2000 Systems
A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 CEA Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.
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Table 1: Substantial Equivalence Comparison
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 CEA CVM | Predicate DeviceIMMULITE 2000 DHEA-SO4CVM | |
| IntendedUse | The IMMULITE® CEA CalibrationVerification Material (CVM) is for invitro diagnostic use in the verificationof calibration of the IMMULITE CEAassay on the IMMULITE 2000systems. | The IMMULITE® DHEA-SO4Calibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration ofthe IMMULITE DHEA-SO4 assayon the IMMULITE 2000 systems. |
| Form | Lyophilized | Same |
| Storage | ≤-20°C | Same |
| Matrix | Human Serum with preservatives | Same |
| Stability | Stable unopened until theexpiration date | Same |
| Levels | 4 | Same |
| Use | Single Use Only | Same |
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 CEA CVM | Predicate DeviceIMMULITE 2000 DHEA-SO4CVM | |
| Analyte | CEA | DHEA-SO4 |
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7. Non-Clinical Performance Testing
Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intended use. The following tests were performed on the candidate device.
7.1 Stability Summary:
The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 CEA 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 IMMULITE® 2000 CEA Calibration Verification Materials are stable up to 6 years when stored at -20°C prior to opening and for 8 hours at ambient or room temperature (15-25°C) after reconstitution.
7.1.1 Stability Protocol Summary:
The CVM study protocols are run as part of the calibrator stability testing. Three lots of stability CVMs and reference CVMs are run in duplicate (as a minimum) at the time points shown in Tables 2a. 2b and 2c and the dose value determined from the reference calibrator curve.
| CVM level | Time-Points (months) | |||
|---|---|---|---|---|
| LCECVM1 | Day 0 | 60 | 72 | 108 |
| LCECVM2 | Day 0 | 60 | 72 | 108 |
| LCECVM3 | Day 0 | 60 | 72 | 108 |
| LCECVM4 | Day 0 | 60 | 72 | 108 |
Table 2a: Stability Time Points for CEA CVM lot 006
Table 2b: Stability Time Points for CEA CVM lot 007
| CVM level | Time-Points (months) | |||
|---|---|---|---|---|
| LCECVM1 | Day 0 | 48 | 60 | 84 |
| LCECVM2 | Day 0 | 48 | 60 | 84 |
| LCECVM3 | Day 0 | 48 | 60 | 84 |
| LCECVM4 | Day 0 | 48 | 60 | 84 |
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| CVM level | Time-Points (months) | |||
|---|---|---|---|---|
| LCECVM1 | Day 0 | 4 | 5 | 6 |
| LCECVM2 | Day 0 | 4 | 5 | 6 |
| LCECVM3 | Day 0 | 4 | 5 | 6 |
| LCECVM4 | Day 0 | 4 | 5 | 6 |
Table 2c: Stability Time Points for CEA CVM lot 090
For Open Component testing, the results are determined from a 2-point adjustment. Using IMMULITE 2000 CEA kit lot 290, CEA CVM lot 090 was tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions and compared to the determinations at time zero.
7.1.2 Stability Acceptance Criteria Summary:
The guideline criteria for samples stored over time at -20°C is outlined in Table 3.
The Acceptance Criteria for the IMMULITE CEA CVM real time and open component stability testing is applied to dose compared to dose at time point zero. The result is required to fall between ±10% difference for CVM levels 2 and 3 and ±15% for CVM level 4.
If the guideline criteria fail, then the stability is assessed on analyte drift as described below:
- If the slope is not significant (p ≥ 0.05), the stability estimate is the study duration less one time unit.
- If the slope is significant (p < 0.05), the stability claim estimate is taken as the time at ● which the one-sided 95% confidence interval of the regression line intersects with the allowable drift limit for the specific sample.
- The minimum stability estimate across all samples is taken as the stability estimate for that lot.
- The final stability claim for the product is taken as the minimum estimate across all lots from the trend analysis results.
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The acceptance criterion is summarized in Table 3.
|--|
| CVM level | Dose at timepoint 0(ng/mL) | GuidelineCriteria% difference todose attime point 0 | Acceptabledose range(ng/mL) | ||
|---|---|---|---|---|---|
| LCECVM1 | 006007090 | 0.00 | Not Applicable | ≤0.2 | |
| LCECVM2 | 006 | 3.04 | ±10% | 2.74 - 3.34 | |
| 007 | 2.54 | 2.28 - 2.79 | |||
| 090 | 3.04 | 2.74 - 3.34 | |||
| LCECVM3 | 006 | 94.2 | ±10% | 84.8 - 103.6 | |
| 007 | 91.7 | 82.5 - 101 | |||
| 090 | 96.7 | 87.0 - 106 | |||
| LCECVM4 | 006 | 633 | ±15% | 538 - 728 | |
| 007 | 602 | 512 - 692 | |||
| 090 | 596 | 507 - 685 |
7.2 Traceability:
The IMMULITE CEA CVMs are traceable to an internal standard. The CVMs are manufactured using qualified materials and measurement procedures.
7.3 Value Assignment:
IMMULITE CEA CVMs are 4 level materials which are a subset of 7 level CEA calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of CEA 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 CEA antigen stock and are traceable to an internal standard which have been gravimetrically prepared. Nine levels of commercially available controls and 21 samples (5 normal and 21 spiked samples) were used to validate calibrator/CVM value assignments.
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The CVMs are manufactured using qualified materials and measurement procedures. The IMMULITE CEA calibrators/CVMs were tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, 9 IMMULITE 2000 systems and 5 different reagent kit lots.The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The controls must fall within their target ranges.
7.4 Expected Values/Reference Range:
Each CVM level was tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, 9 IMMULITE 2000 systems and 5 different reagent kit lots. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration Verification Material lot-specific package insert.
The expected assay range is up to 550 ng/mL. The target values in Table 4 can be considered as guidelines.
| Analyte | CVM Level | Target | Standard | Guideline ±2SD Range | |
|---|---|---|---|---|---|
| target levels | Mean | Deviation | (ng/mL) | ||
| (ng/mL) | (SD) | ||||
| LCECVM1 | 0.00 | 0.00 | <0.20 | ||
| LCECVM2 | 2.51 | 0.25 | 2.01 | 3.01 | |
| LCECVM3 | 92.0 | 5.5 | 81 | 103 | |
| LCECVM4 | 600 | વર્સ | 510 | 690 | |
| Assay Range | Up to 550 ng/mL |
Table 4: Target Values
Each laboratory should establish their limits for acceptability based on methodology, clinical significance and medical decision levels of the test analyte. The representative, total precision tabulated in the respective assay instructions for use may be considered as one factor when establishing local, acceptable ranges. The values provided above may be considered as guidelines. Value assignment is lot specific.
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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
Conclusion: 8.
The IMMULITE® 2000 CEA 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 DHEA-SO4 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 CEA 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.