(49 days)
The IMMULITE® Rubella Quantitative IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Rubella Quantitative IgG assay on the IMMULITE 2000 systems.
The IMMULITE® H. pylori IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE H. pylori IgG assay on the IMMULITE 2000 systems.
The IMMULITE® Toxoplasma Quantitative IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Toxoplasma Quantitative IgG assay on the IMMULITE 2000 systems.
IMMULITE® 2000 Rubella Quantitative IgG Calibration Verification Material (CVM) contains one set of four vials each 1.0mL. CVM1 contains negative Rubella IgG in human serum and a buffered bovine protein matrix with preservatives. CVM2, CVM 3 and CVM4 contain various levels of Rubella IgG in human serum and buffered bovine protein matrix with preservatives.
IMMULITE® 2000 H. pylori IgG Calibration Verification Material (CVM) contains one 1 mL vial. CVM 1 contains H. pylori IgG in human serum and a buffered bovine protein matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 1 mL each. CVM1 contains negative Toxoplasma IgG in human serum in a bovine protein/buffer matrix with preservatives. CVM2, CVM3 and CVM4 contain various levels of Toxoplasma IgG in human serum in a bovine protein/buffer matrix with preservatives.
Here's an analysis of the provided text regarding the acceptance criteria and supporting studies for the IMMULITE® 2000 Calibration Verification Materials.
It's important to note that this document describes Calibration Verification Materials (CVMs), which are quality control materials used to verify the calibration of existing assays, not diagnostic devices that produce patient results. Therefore, many standard questions about diagnostic device studies (like expert ground truth, MRMC studies, standalone performance, training sets, etc.) are not applicable in this context. The focus here is on the stability and accuracy of the CVMs themselves.
Acceptance Criteria and Reported Device Performance
The document describes three distinct Calibration Verification Materials (CVMs): IMMULITE® 2000 Rubella Quantitative IgG CVM, IMMULITE® 2000 H. pylori IgG CVM, and IMMULITE® 2000 Toxoplasma Quantitative IgG CVM. Each has specific acceptance criteria for stability testing.
1. Table of Acceptance Criteria and Reported Device Performance:
| CVM Level/Analyte | Acceptance Criteria (Guideline Criteria) | Acceptable Dose Range (IU/mL or U/mL) | Reported Performance (Stability Claim) |
|---|---|---|---|
| IMMULITE® 2000 Rubella Quantitative IgG CVM | |||
| LRUBCVM1 | Not Applicable (≤5.00 IU/mL) | ≤5.00 | Stable up to 30 months at -20°C (unopened), 8 hours at 15-25°C (open) |
| LRUBCVM2 | ±15% difference to assigned dose | 7.65 - 10.4 | (Met the criteria, as implied by the FDA clearance) |
| LRUBCVM3 | ±15% difference to assigned dose | 208 – 282 | (Met the criteria, as implied by the FDA clearance) |
| LRUBCVM4 | ±20% difference to assigned dose | 404 - 606 | (Met the criteria, as implied by the FDA clearance) |
| Review Limits | Controls are within 2SD of target on each curve | N/A | (Met if guideline criteria not met, as implied by clearance) |
| IMMULITE® 2000 H. pylori IgG CVM | |||
| LHPGCVM1 | ±10% difference to assigned dose | 0.96 – 1.18 U/mL | Stable up to 24 months at -20°C (unopened), 8 hours at 15-25°C (open) |
| IMMULITE® 2000 Toxoplasma Quantitative IgG CVM | |||
| LTXPCVM1 | Not Applicable (≤5.00 IU/mL) | ≤5.00 | Stable up to 3 years at -20°C (unopened), 8 hours at 15-25°C (open) |
| LTXPCVM2 | ±10% difference to assigned dose | 9.5 - 11.7 | (Met the criteria, as implied by the FDA clearance) |
| LTXPCVM3 | ±10% difference to assigned dose | 66.2 – 80.9 | (Met the criteria, as implied by the FDA clearance) |
| LTXPCVM4 | ±24% difference to assigned dose | 281 - 459 | (Met the criteria, as implied by the FDA clearance) |
| Review Limits | Controls are within 2SD of target on each curve | N/A | (Met if guideline criteria not met, as implied by clearance) |
Note on "Reported Performance": The document states that "Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intended use" and implies that these criteria were met, leading to FDA clearance. The specific numerical performance data results demonstrating adherence to these criteria are not provided in the summary, only the criteria themselves and the resulting stability claims.
Supporting Study Information (Where Applicable)
As these are Calibration Verification Materials, the "study" referred to is primarily stability testing and value assignment validation. Many of the typical questions for diagnostic devices are not relevant here.
2. Sample size used for the test set and data provenance:
- Test Set Description: The "test set" for performance evaluation consists of the CVM lots themselves, tested over time and under various conditions (different IMMULITE 2000 systems, reagent kit lots).
- Rubella CVM: CVM lot 090 tested with L2KRUB kit lot 432.
- H. pylori CVM: CVM lot 090 tested with L2KHPG kit lot 341.
- Toxoplasma CVM: CVM lot 090 tested with L2KTXP Kit Lot 394.
- Number of Replicates: For stability time points and expected values, each CVM level was tested on 15 replicates in total, comprised of 5 runs, 3 replicates per run, and across 4 (Rubella, H. pylori) or 5 (Toxoplasma) IMMULITE 2000 systems, and 3 different reagent kit lots.
- Open Component Testing: Tested at 2-hourly intervals for up to 9 hours.
- Data Provenance: Not explicitly stated (e.g., country of origin), but implied to be from Siemens Healthcare Diagnostics' internal testing ("Non-Clinical Performance Testing"). It is a prospective study as it's validating the shelf-life and in-use stability of the product.
3. Number of experts used to establish the ground truth for the test set and qualifications of those experts:
- Not Applicable. For CVMs, the "ground truth" (assigned dose values) is established through traceability to international standards (WHO standards for Rubella and Toxoplasma, gravimetrically prepared internal standard for H. pylori) combined with internal value assignment procedures. This doesn't involve clinical expert consensus on patient diagnoses.
4. Adjudication method for the test set:
- Not Applicable. See point 3. Testing involves objective measurements against established standards and internal quality control ranges, not subjective expert review.
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 device is a quality control material, not an AI-assisted diagnostic tool.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in essence. The performance testing described is of the CVMs themselves, and their ability to verify calibration on the IMMULITE 2000 systems. This is an "algorithm only" type of assessment in the sense that it evaluates the chemical and mechanical performance of the CVMs and the assay system, without direct human interpretation of patient results. The CVM's "performance" is its stability and accurate reflection of a known concentration within the target assay.
7. The type of ground truth used:
- Assigned Reference Calibrators traceable to international standards or gravimetric preparation.
- Rubella IgG CVM: Traceable to WHO 1st IS RUBI-1-94.
- H. pylori IgG CVM: Traceable to an internal standard which has been gravimetrically prepared.
- Toxoplasma Quantitative IgG CVM: Traceable to WHO 3rd IS for Anti-Toxoplasma Serum, Human.
- This ground truth is primarily established through analytical chemistry and metrology, not clinical outcomes or pathology.
8. The sample size for the training set:
- Not Applicable. CVMs are not machine learning models; they do not have a "training set" in the conventional sense. The "training" (development) of the assay itself would involve extensive data, but this document is about the calibration verification materials for that assay.
- For value assignment validation, the following were used:
- Rubella: Three levels of commercially available controls and 42 patient serum samples.
- H. pylori: Three levels of commercially available controls and 24 patient serum samples.
- Toxoplasma: Three levels of commercially available controls and 63 serum samples (40 patient samples and 23 normal samples).
- This "training set" (more accurately, "validation set for value assignment") is used to confirm the accuracy of the CVM's assigned values against real-world samples and other controls.
- For value assignment validation, the following were used:
9. How the ground truth for the training set was established:
- Not Applicable for a training set as these are not ML models.
- For the value assignment validation samples mentioned in point 8:
- The "ground truth" (or target values) for these commercially available controls and patient/normal serum samples would have been established through a combination of reference methods, clinical diagnosis, and highly characterized internal assays, depending on the specific sample. The document states "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." This implies these controls had pre-defined target ranges.
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized human figure or a bird in flight, composed of three overlapping profiles.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
August 19,2014
SIEMENS HEALTHCARE DIAGNOSTICS INC. ASHA GARTLAND 511 BENEDICT AVE. TARRYTOWN NY 10591
Re: K141772 Trade/Device Name: IMMULITE® 2000 Rubella Quantitative IgG Calibration Verification Material IMMULITE® 2000 H. pylori IgG Calibration Verification Material IMMULITE® 2000 Toxoplasma Quantitative IgG 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: June 30, 2014 Received: July 1, 2014
Dear Ms. Gartland:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Sally A. Hojvat -S
Sally A. Hojvat, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number: K141772
Device Name:
IMMULITE® 2000 Rubella Quantitative IgG Calibration Verification Material IMMULITE® 2000 H. pylori IgG Calibration Verification Material IMMULITE® 2000 Toxoplasma Quantitative IgG Calibration Verification Material
Indications for Use:
The IMMULITE® Rubella Quantitative IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Rubella Quantitative IgG assay on the IMMULITE 2000 systems.
The IMMULITE® H. pylori IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE H. pylori IgG assay on the IMMULITE 2000 systems.
The IMMULITE® Toxoplasma Quantitative IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Toxoplasma Quantitative IgG assay on the IMMULITE 2000 systems.
| Prescription Use(21 CFR Part 801 Subpart D) | And/Or | Over the Counter Use(21 CFR Part 801 Subpart C) |
|---|---|---|
| X_ | _ |
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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: | K141772 |
|---|---|
| 1. SubmitterMailing Address: | Siemens Healthcare Diagnostics Inc511 Benedict AvenueTarrytown, NY 10591 |
Asha Gartland Technical Regulatory Affairs Specialist (914)-524-3257 (914)-524-2101 asha.gartland(@siemens.com June 30, 2014
IMMULITE® 2000 Rubella Quantitative IgG Calibration Verification Material
Quality Control materials for IMMULITE® 2000 Rubella Quantitative IgG assay Calibration Verification Material (CVM) for IMMULITE® 2000 Rubella Quantitative IgG assay 21 CFR 862.1660, Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Microbiology (83)
IMMULITE® 2000 HCG Calibration Verification Material (CVM) K133128
The Calibration Verification Material (CVM) contains one set of four vials each 1.0mL. CVM1 contains negative Rubella IgG in human serum and a buffered bovine protein matrix with preservatives. CVM2, CVM 3 and CVM4 contain various levels of Rubella IgG in human serum and buffered bovine protein matrix with preservatives.
Contact Person:
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:
4. Device Description:
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Image /page/4/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 presented in all capital letters and is horizontally oriented.
| 5. Intended Use: | See Indications for Use Statement below: |
|---|---|
| Indication for Use: | The IMMULITE® Rubella Quantitative IgG Calibration VerificationMaterial (CVM) is for in vitro diagnostic use in the verification ofcalibration of the IMMULITE Rubella Quantitative IgG assay on theIMMULITE 2000 systems. |
| Special Conditions for | |
| Use Statement(s):Special Instrument | For prescription use only |
| Requirements: | IMMULITE® 2000 Systems |
| 6. Technological Characteristics | |
| and Substantial Equivalence | A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Rubella Quantitative IgG Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in |
| Comparison with Predicate: |
Table 1.
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| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 RubellaQuantitative IgG CVM | Predicate DeviceIMMULITE 2000 HCG CVM | |
| IntendedUse | The IMMULITE® RubellaQuantitative IgG CalibrationVerification Material (CVM) is for invitro diagnostic use in the verificationof calibration of the IMMULITERubella Quantitative IgG assay on theIMMULITE 2000 systems. | The IMMULITE® HCG CalibrationVerification Material (CVM) is for invitro diagnostic use in the verificationof calibration of the IMMULITEHCG assay on the IMMULITE 2000systems. |
| Form | Liquid | Same |
| Storage | ≤20°C | Same |
| Stability | Stable unopened until the expirationdate | Same |
| Levels | 4 | Same |
| Use | Single Use Only | Same |
Table 1: Substantial Equivalence Comparison
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 RubellaQuantitative IgG CVM | Predicate DeviceIMMULITE 2000 HCG CVM | |
| Analyte | Rubella IgG | HCG |
| Matrix | Human serum with Bovine protein andpreservatives | Human serum with preservatives |
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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 the real-time shelf life and In-Use (Open Component or open vial) claim for the IMMULITE 2000 Rubella Quantitative IgG 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 opening. The IMMULITE® 2000 Rubella Quantitative IgG Calibration Verification Materials are stable up to up to 30 months (2.5 years) when stored at -20°C prior to opening and for 8 hours at ambient or room temperature (15-25°C) after opening.
7.1.1 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) | |||
|---|---|---|---|---|
| LRUBCVM1 | 0 | 18 | 24 | 30 |
| LRUBCVM2 | 0 | 18 | 24 | 30 |
| LRUBCVM3 | 0 | 18 | 24 | 30 |
| LRUBCVM4 | 0 | 18 | 24 | 30 |
Table 2: Stability Time Points
For Open Component testing, the results are determined from 2-point adjustment. Using IMMULITE 2000 Rubella Quantitative IgG kit (L2KRUB) lot 432, CVM lot 090 were tested at 2hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.
7.1.2 Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE Rubella IgG CVM are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability calibrator/CVM levels 2 and 3 to fall between ±15% of assigned dose and ±20% of assigned dose for level 4. Part 2 review limits criteria require dose value of the controls to be within 2 Standard Deviation (SD) of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±15% for levels 2 and ±20% for level 4 then additional data review is conducted using part 2 criteria. The acceptance criterion is summarized in Table 3.
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| CVM level | AssignedDose(IU/mL) | *Guideline Criteria% difference toassigned dose | Acceptable doserange(IU/mL) | **ReviewLimits |
|---|---|---|---|---|
| LRUBCVM1 | 0.00 | Not Applicable | ≤5.00 | Controls arewithin 2SDof target oneach curve |
| LRUBCVM2 | 9.00 | ±15% | 7.65 - 10.4 | Controls arewithin 2SDof target oneach curve |
| LRUBCVM3 | 245 | ±15% | 208 – 282 | Controls arewithin 2SDof target oneach curve |
| LRUBCVM4 | 505 | ±20% | 404 - 606 | Controls arewithin 2SDof target oneach curve |
Table 3 Acceptance criteria for stability of IMMULITE 2000 Rubella Quantitative IgG CVM
7.2 Traceability:
The IMMULITE Rubella Quantitative IgG CVMs are traceable to WHO 1st IS RUBI-1-94. The CVMs are manufactured using qualified materials and measurement procedures.
7.3 Value Assignment:
IMMULITE Rubella Quantitative IgG CVMs are 4 level materials which are a subset of 7 level Rubella Quantitative IgG calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Rubella Quantitative IgG 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 Rubella Quantitative IgG antigen stock and are traceable to WHO 1st IS RUBI-1-94. Three levels of commercially available controls and 42 patient serum samples were used to validate calibrator/CVM value assignments.
The CVMs are manufactured using qualified materials and measurement procedures. The IMMULITE Rubella Quantitative IgG calibrators/CVMs were tested on 15 replicates in total, comprised of 5 runs, 3 replicates per run, 4 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 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 15 replicates in total comprised of 5 runs, 3 replicates per run, 4 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 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration Verification Material lot-specific package insert.
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The expected assay range is 5 to 400 IU/mL. The target values in Table 4 can be considered as guidelines.
| Analytetarget levels | CVM Level | Target Mean(IU/mL) | StandardDeviation(SD) | Guideline ±2SD Range(IU/mL) | |
|---|---|---|---|---|---|
| LRUBCVM1 | 0.00 | - | 0.00 $\leq$ 5.00 | ||
| LRUBCVM2 | 9.15 | 0.92 | 7.32 | 11.0 | |
| LRUBCVM3 | 195 | 14.5 | 166 | 224 | |
| LRUBCVM4 | 425 | 42.5 | 340 | 510 | |
| Assay Range | 5 to 400 IU/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.
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 Rubella Quantitative IgG 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 HCG 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 Rubella Quantitative IgG Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.
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510(k) Summary
Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.
The assigned 510(k) Number: K141772
| 1. Submitter | |
|---|---|
| Mailing 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: | June 30th, 2014 |
| 2. Device Name | |
| Proprietary Name: | IMMULITE® 2000 H. pylori IgG Calibration Verification Material |
| Measurand: | Material |
| Type of Test: | Quality Control material for IMMULITE® 2000 H. pylori IgG assayCalibration Verification Material (CVM) for IMMULITE® 2000H. pylori IgG 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: | Microbiology (83) |
| 3. Predicate Device Name | IMMULITE® 2000 HCG Calibration Verification Material (CVM) |
| Predicate 510(k) No: | K133128 |
| 4. Device Description: | IMMULITE® 2000 H. pylori IgG Calibration Verification Material (CVM) contains one 1 mL vial. CVM 1 contains H. pylori IgG in human serum and a buffered bovine protein matrix with preservatives. |
| 5. Intended Use: | |
| Indication for Use: | See Indications for Use Statement belowThe IMMULITE® H. pylori IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE H. pylori IgG assay on the IMMULITE 2000 systems. |
| Special Conditions forUse Statement(s): | For prescription use only |
| Special InstrumentRequirements: | IMMULITE® 2000 Systems |
| 6. Technological |
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Image /page/10/Picture/0 description: The image shows the word "SIEMENS" in a large, sans-serif font. The letters are a teal color, and the word is underlined with a thin black line. The background is white.
| Characteristics andSubstantial EquivalenceComparison with Predicate: | A comparison of the device features, intended use, and otherinformation demonstrates that the IMMULITE® 2000 H. pylori IgGCalibration Verification Material (CVM) is substantially equivalent tothe predicate device as summarized in Table 1. |
|---|---|
| ------------------------------------------------------------------------------ | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
Table 1: Substantial Equivalence Comparison
| SIMILARITIES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 H. pylori IgG CVM | Predicate DeviceIMMULITE 2000 HCG CVM | |
| Intended Use | The IMMULITE® H. pylori IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE H. pylori IgG assay on the IMMULITE 2000 systems | The IMMULITE® HCG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE HCG assay on the IMMULITE 2000 systems |
| Form | Liquid | Same |
| Storage | ≤20°C | Same |
| Stability | Stable unopened until the expiration date | Same |
| Levels | 4 | Same |
| Use | Single Use Only | Same |
| Form | Liquid | Same |
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 H. pylori IgG CVM | Predicate DeviceIMMULITE 2000 HCG CVM | |
| Analyte | H. pylori IgG | HCG |
| Matrix | Human serum with Bovine protein andpreservatives | Human serum with preservatives |
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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) for the IMMULITE 2000 H. pylori IgG 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 opening.
The H. pylori IgG Calibration Verification Material is stable up to 24 months (2 years) when stored at -20°C prior to opening, and stable for 8 hours at ambient or room temperature (15-25°C) after opening.
7.1.1 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) | |||
|---|---|---|---|---|
| LHPGCVM1 | 0 | 12 | 18 | 24 |
| LHPGCVM1 | 0 | 12 | 18 | 24 |
| LHPGCVM1 | 0 | 12 | 18 | 24 |
| LHPGCVM1 | 0 | 12 | 18 | 24 |
Table 2: Stability Time Points
For Open Component testing, the results are determined from 2-point adjustment. Using IMMULITE 2000 H. pylori IgG (L2KHPG) kit Lot 341, the Lot 090 CVM was tested at 2hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.
7.1.2 Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE H. pylori IgG CVM criteria require the dose value of stability calibrator/CVM to fall within ±10% of the assigned dose.
The acceptance criterion is summarized in Table 3.
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| CVM level | AssignedDose(U/mL) | GuidelineCriteria% difference toassigned dose | Acceptabledose range(U/mL) |
|---|---|---|---|
| LHPGCVM1 | 1.07 | ±10% | 0.96 – 1.18 |
|--|
7.2 Traceability:
The IMMULITE H. pylori IgG CVM is traceable to an internal standard which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.
7.3 Value Assignment:
H. pylori IgG CVM is a single level material; one level of 7 level H. pylori IgG calbrators. Calibrators are not commercialized but are used internally during manufacture and release testing of H. pylori IgG 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 H. pvlori IgG antigen stock and are traceable to an internal material which has been gravimetrically prepared. Three levels of commercially available controls and 24 patient serum samples were used to validate calibrator/CVM value assignments.
The 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, 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. CVM values are then averaged across all systems. Ouality 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.
7.4 Expected Values/Reference Range:
Each CVM level was tested 15 replicates in total, comprised of 5 runs, 3 replicates per run, 4 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
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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 0.4 to 8.0 U/mL. The target values in Table 4 can be considered as guidelines.
| Analyte targetlevels | CVM Level | Target (U/mL) | StandardDeviation(SD) | Guideline ±2SDRange(U/mL) |
|---|---|---|---|---|
| LHPGCVM1 | 1.07 | 0.05425 | 0.963 1.18 | |
| Assay Range | 0.4 to 8.0 U/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.
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 H. pylori IgG Calibration 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 HCG 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 H. pylori IgG Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.
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510(k) Summary
Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence. The assigned 510(k) Number: K141772
| 1. SubmitterMailing Address: | Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591 |
|---|---|
| Contact Person:Phone Number:Fax Number:E-mail Address:Date Prepared: | Asha GartlandTechnical Regulatory Affairs Specialist(914)-524-3257(914)-524-2101asha.gartland@siemens.comJune 30th, 2014 |
| 2. Device NameProprietary Name:Measurand:Type of Test:Regulation Section:Classification:Products Code:Panel: | IMMULITE® 2000 Toxoplasma Quantitative IgG CalibrationVerification MaterialQuality Control materials for IMMULITE® 2000 ToxoplasmaQuantitative IgG assayCalibration Verification Material (CVM) for IMMULITE® 2000Toxoplasma Quantitative IgG assay21 CFR 862.1660, Quality Control MaterialClass I ReservedJJX - Single (Specified) Analyte Controls (Assayed andUnassayed)Microbiology (83) |
| 3. Predicate Device Name | IMMULITE® 2000 HCG Calibration Verification Material (CVM)K133128 |
| Predicate 510(k) No:4. Device Description: | The Calibration Verification Material (CVM) contains one set offour vials, 1 mL each. CVM1 contains negative Toxoplasma IgGin human serum in a bovine protein/buffer matrix withpreservatives. CVM2, CVM3 and CVM4 contain various levels ofToxoplasma IgG in human serum in a bovine protein/buffer matrixwith preservatives. |
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| 5. Intended Use:Indication for Use: | See Indications for Use Statement belowThe IMMULITE® Toxoplasma Quantitative IgG CalibrationVerification Material (CVM) is for in vitro diagnostic use in theverification of calibration of the IMMULITE ToxoplasmaQuantitative IgG assay on the IMMULITE 2000 systems |
|---|---|
| Special Conditions forUse Statement(s):Special InstrumentRequirements: | For prescription use onlyIMMULITE® 2000 Systems |
| 6. TechnologicalCharacteristics andSubstantial EquivalenceComparison with Predicate: | A comparison of the device features, intended use, and otherinformation demonstrates that the IMMULITE® 2000 ToxoplasmaQuantitative IgG Calibration Verification Material (CVM) issubstantially equivalent to the predicate device as summarized inTable 1. |
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| SIMILARITIES | |||
|---|---|---|---|
| Candidate DeviceIMMULITE 2000 ToxoplasmaQuantitative IgG CVM | Predicate DeviceIMMULITE HCG CVM | ||
| IntendedUse | The IMMULITE® ToxoplasmaQuantitative IgG CVM CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration of the IMMULITEToxoplasma Quantitative IgG assay on theIMMULITE 2000 systems | The IMMULITE® HCGCalibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration ofthe IMMULITE HCG assay on theIMMULITE 2000 systems. | |
| Form | Liquid | Same | |
| Levels | 4 | Same | |
| Stability | Stable unopened until the expiration date | Same | |
| Use | Single Use Only | Same | |
| Storage | <20°C | Same |
| Table 1: Substantial Equivalence Comparison | |||
|---|---|---|---|
| -- | -- | --------------------------------------------- | -- |
| DIFFERENCES | ||
|---|---|---|
| Candidate DeviceIMMULITE 2000 ToxoplasmaQuantitative IgG CVM | Predicate DeviceIMMULITE HCG CVM | |
| Analyte | Toxoplasma Quantitative IgG | HCG |
| Matrix | Human serum with Bovine proteinand preservatives | Human serum with preservatives |
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 real time stability study was conducted to validate shelf life claim and In-Use (Open Component or open vial) claim for the IMMULITE 2000 Toxoplasma Quantitative IgG 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 opening. The IMMULITE® 2000 Toxoplasma Quantitative IgG Calibration
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Verification Materials (CVMs) are up 3 years when stored at -20℃ prior to opening and stable for 8 hours at ambient or room temperature (15-25℃) after opening.
7.1.1 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) | |||
|---|---|---|---|---|
| LTXPCVM1 | 0 | 24 | 30 | 36 |
| LTXPCVM2 | 0 | 24 | 30 | 36 |
| LTXPCVM3 | 0 | 24 | 30 | 36 |
| LTXPCVM4 | 0 | 24 | 30 | 36 |
Table 2: Stability Time Points
For Open Component testing, the results are determined from 2-point adjustment. Using L2KTXP Kit Lot 394, Lot 090 CVMs were tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.
7.1.2 Stability Acceptance Criteria Summary:
The Acceptance Criteria for the IMMULITE 2000 Toxoplasma Quantitative IgG CVM are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability calibrator/CVM levels 2 and 3 to fall between ±10% of assigned dose and ±24% for level 4. Part 2 review limits criteria 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 ±10% for levels 2 and ±24% for level 4 then additional data review is conducted using part 2 criteria.
The acceptance criterion is summarized in Table 3.
| CVM level | AssignedDose(IU/mL) | *Guideline Criteria% difference toassigned dose | Acceptable doserange (pg/mL)(IU/mL) | ReviewLimits |
|---|---|---|---|---|
| LTXPCVM1 | 0.00 | Not Applicable | ≤5.00 | Controls arewithin 2SDof target oneach curve |
| LTXPCVM2 | 10.6 | ±10% | 9.5 - 11.7 | |
| LTXPCVM3 | 73.5 | ±10% | 66.2 — 80.9 | |
| LTXPCVM4 | 370 | ±24% | 281 - 459 |
Table 3: Acceptance criteria for stability of IMMULITE 2000 Toxoplasma Quantitative IgG CVM
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7.2 Traceability:
The IMMULITE Toxoplasma Quantitative IgG calibrators and therefore CVMs are value assigned using assigned reference calibrators and are traceable to WHO 3rd IS for Anti-Toxoplasma Serum, Human. The calibrators/CVMs are manufactured using qualified materials and measurement procedures.
7.3 Value Assignment:
IMMULITE Toxoplasma Quantitative IgG CVMs are 4 level materials which are a subset of 6 level Toxoplasma Quantitative IgG calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Toxoplasma Quantitative IgG 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 human serum with IgG positive to Toxoplasma and human serum with IgG negative to Toxoplasma which are combined and spiked in the buffered bovine protein matrix. Three levels of commercially available controls and 63 serum samples (40 patient samples and 23 normal samples) were used to validate calibrator/CVM value assignments.
The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 15 replicates in total, comprised of 5 runs, 3 replicates per run, 5 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. 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.
7.4 Expected Values/Reference Range:
Each CVM level was tested on 15 replicates in total comprised of 5 runs, 3 replicates per run, 5 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 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 Toxoplasma Quantitative IgG CVM Calibration Verification Material lot-specific package insert. The expected assay range is 5 to 250 IU/mL. The target values in Table 4 can be considered as guidelines.
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| Analyte targetlevels | CVM Level | Target Mean(IU/mL) | StandardDeviation(SD) | Guideline ±2SD Range(IU/mL) |
|---|---|---|---|---|
| LTXPCVM1 | 0.00 | - | 0.00 $\leq$ 5.00 | |
| LTXPCVM2 | 10.1 | 0.7525 | 8.59 11.6 | |
| LTXPCVM3 | 73.5 | 5.5 | 62.5 84.5 | |
| LTXPCVM4 | 272 | 32.5 | 207 337 | |
| Assay Range | 5 to 250 IU/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.
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 Toxoplasma Quantitative IgG 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 HCG 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 Toxoplasma Quantitative IgG 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.