(34 days)
The ADVIA Centaur® IgE Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Total IgE assay.
ADVIA Centaur® IgE Master Curve Material is an in vitro diagnostic product containing various levels of IgE spiked in lyophilized human plasma with sodium azide (0.1%) and preservatives. Each set contains seven levels (MCM1–7); with a reconstituted volume of 1.0 mL/vial per level. MCM1 contains no analyte. The MCMs assigned values are lot-specific of target values: 0.0, 12.5, 40.0, 270, 1000, 1700, and 3150 IU/mL.
This document describes the ADVIA Centaur® IgE Master Curve Material (MCM), a quality control material used for in vitro diagnostic verification of calibration and reportable range of the ADVIA Centaur Total IgE assay. It is not an AI/ML device, and therefore several of the requested sections (e.g., sample size for test/training sets, number/qualifications of experts, adjudication methods, MRMC studies, standalone algorithm performance, data provenance) are not applicable.
Here's a breakdown of the available information:
1. Table of Acceptance Criteria and Reported Device Performance
The device is a quality control material, not a diagnostic test with metrics like sensitivity or specificity. Its performance is measured by its stability and its ability to be correctly value-assigned.
| Performance Metric | Acceptance Criteria (Sponsor's Required Acceptance Criteria) | Reported Device Performance |
|---|---|---|
| Real Time/Shelf Life Stability | MCM1 dose recovery ≤ 2.0 IU/mL; MCM2-7 % dose recovery met sponsor's required acceptance criteria. | Current testing meets the sponsor's acceptance criteria for the real-time stability study up to the 9 months' time point, supporting an 8-month shelf-life claim when stored unopened at 2-8°C. |
| In-Use Open Vial (Reconstituted) Stability | MCM1 dose recovery < 2.0 IU/mL; MCM2-7 % dose recovery met sponsor's required acceptance criteria. | Acceptance criteria for the open vial (reconstituted) stability study were met up to the 29 days' time point, supporting an open vial claim of 28 days when properly stored at 2-8°C. |
| On-Board Stability | MCM1 dose recovery ≤ 2.0 IU/mL; MCM2-7 % dose recovery met sponsor's required acceptance criteria. | Acceptance criteria for the on-board stability study were met up to 5 hours, which supports an on-board stability claim for 4 hours. |
| Value Assignment (MCM1) | MCM1 measures at or below the IgE assay sensitivity limit. (Target: 0.0 dose) | Consistent with claim: MCM1 is an analyte-free basepool and its quality control specifications ensure it measures at or below the IgE assay sensitivity limit. |
| Value Assignment (MCM2-MCM7) | New MCM doses must fall within the final value assignment specification for IgE MCMs. The mean MCM doses of the new MCM lot manufactured must fall within the customer range specifications. | New MCM doses are calculated based on the relationship between observed reference MCM dose and its assigned value. Performance verification runs confirm meeting customer range specifications. Table 2 provides assigned target values for each MCM level, demonstrating this aspect of performance. |
2. Sample Size Used for the Test Set and the Data Provenance
This is not applicable as the device is a quality control material, not a diagnostic test evaluated with a patient test set. The "testing" refers to internal laboratory performance studies to validate the stability and value assignment of the quality control material itself.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
Not applicable. Ground truth, in this context, relates to the accurate assignment of IgE values to the control materials, which is done through a standardized, traceable process rather than expert consensus on patient data.
4. Adjudication Method (e.g. 2+1, 3+1, none) for the Test Set
Not applicable.
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 quality control material, not an AI/ML diagnostic device for human reader assistance.
6. If a standalone (i.e., algorithm only without human-in-the loop performance) was done
Not applicable. This is not an algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "ground truth" for the ADVIA Centaur® IgE Master Curve Material is established through traceability to a recognized international standard: the World Health Organization (WHO) 75/502 reference material for IgE. This means the values assigned to the quality control material are linked to a globally accepted standard, ensuring consistency and accuracy.
8. The sample size for the training set
Not applicable. There is no "training set" as this is not an AI/ML model.
9. How the ground truth for the training set was established
Not applicable.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
January 27, 2015
Siemens Healthcare Diagnostics, Inc. c/o Ms. Fatima Pacheco Regulatory Clinical Affairs Specialist 511 Benedict Avenue Tarrytown, NY 10591
Re: K143680
Trade/Device Name: ADVIA Centaur® IgE Master Curve 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: January 5, 2015
Dear Ms. Pacheco:
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 Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set
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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 -A
Leonthena Carrington, MS, MBA, MT (ASCP) Director (Acting) 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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Indications for Use
510(k) Number (if known) K143680
Device Name
ADVIA Centaur® IgE Master Curve Material
Indications for Use (Describe)
The ADVIA Centaur® IgE Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Total IgE assay.
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)
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SIEMENS
510(k) Summary
510(k) Summary – ADVIA Centaur IgE Master Curve Material
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: K143680
| 1. Applicant Information | Siemens Healthcare Diagnostics Inc. |
|---|---|
| Mailing Address: | 511 Benedict AvenueTarrytown, NY 10591 USA |
| Contact Person: | Fatima PachecoRegulatory Clinical Affairs Specialist |
| Phone Number: | (914) 524-2450 |
| Fax Number: | (914) 524-3579 |
| E-mail Address: | fatima.pacheco@siemens.com |
| Date Prepared: | January 26, 2015 |
| 2. Device Name | |
| Proprietary Name: | ADVIA Centaur® IgE Master Curve Material |
| Measurand: | Quality Control materials for ADVIA Centaur IgE assay |
| Type of Test: | Master Curve Material (MCM) for ADVIA Centaur IgE assay21 CFR 862.1660, Quality Control Material |
| Regulation Section: | Class I Reserved |
| Classification: | JJX - Single (Specified) Analyte Controls (Assayed andUnassayed) |
| Products Code: | Unassayed) |
| Panel: | Immunology (82) |
| 3. Predicate Device Name | IMMULITE 2000 Total IgE Calibration Verification Material(CVM) |
| Predicate 510(k) No: | K133122 |
| 4. Device Description: | ADVIA Centaur® IgE Master Curve Material is an in vitrodiagnostic product containing various levels of IgE spiked inlyophilized human plasma with sodium azide (0.1%) andpreservatives. Each set contains seven levels (MCM1–7); with areconstituted volume of 1.0 mL/vial per level. MCM1containsno analyte. The MCMs assigned values are lot-specific of target |
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SIEMENS
| values: 0.0, 12.5, 40.0, 270, 1000, 1700, and 3150 IU/mL. | |
|---|---|
| 5. Intended Use:Indication for Use: | See Indications for Use Statement below:The ADVIA Centaur® IgE Master Curve Material is for in vitrodiagnostic use in the verification of calibration and reportablerange of the ADVIA Centaur Total IgE assay. |
| Special Conditions forUse Statement(s): | For prescription use only |
| Special InstrumentRequirements: | ADVIA Centaur® SystemsA description of the ADVIA Centaur system is documentedin K971418. Subsequent modifications to the instrument havebeen reviewed and cleared in K032525 and K041133. |
| 6. Technological Characteristicsand Substantial EquivalenceComparison with Predicate: | A comparison of the device features, intended use, and otherinformation demonstrates that the ADVIA Centaur IgE MCM issubstantially equivalent to the predicate device as summarizedin Table 1. |
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| SIMILARITIES | ||
|---|---|---|
| Candidate Device | Predicate Device | |
| Item | ADVIA Centaur IgE MCM | IMMULITE 2000 Total IgECalibration Verification Material(CVM) |
| IntendedUse | The ADVIA Centaur IgE Master CurveMaterial is for in vitro diagnostic use inthe verification of calibration andreportable range of the ADVIACentaur tIgE assay. | The IMMULITE 2000 Total IgECalibration Verification Material(CVM) is intended for in vitrodiagnostic use, as a control forcalibration verification of theIMMULITE 2000 Total IgE assay onIMMULITE 2000 systems asindicated in the CVM Package Insert. |
| Analyte | IgE | Same |
| DIFFERENCES | ||
| Form | Lyophilized | Liquid |
| Storage | 2-8°C | ≤ -20°C |
| Use | Multiple Use | Single Use |
| Matrix | Human plasma | Equine serum |
| Levels | 7 | 4 |
| Stability | Unopened - Stable when storedunopened at 2-8°C for 8 months.Opened (Reconstituted) – Stablewhen stored at 2-8°C for 28 days; oron-board for 4 hours. | Unopened - Stable until theexpiration date on the vial. |
Table 1: Substantial Equivalence Comparison
7. Standard/Guidance Document References
The following recognized standard and guidance documents were used:
- Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic ● Calibrators
- Guidance for Industry and FDA Staff Assayed and Unassayed Quality Control ● Material
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8. Test Principle
The MCMs are specifically intended for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur assays for use on the ADVIA Centaur systems. Customers may use MCMs for bi-annual calibration verification checks of the assay range and linearity in order to meet the requirements of hospital accreditation bodies.
9. Performance Characteristics
9.1 Analytical performance:
The following studies are not applicable for the purpose of this submission:
- Precision/Reproducibility ●
- Linearity/Assay Reportable Range .
- Detection limit ●
- Analytical Specificity ●
- Assay cut-off ●
- Method Comparison Studies ●
- Clinical Studies (Sensitivity, Specificity, and cut-off) ●
9.2 Non-Clinical Performance Testing
9.2.1 Stability Studies
Stability studies were conducted on the ADVIA Centaur system to support the shelf life (unopened) and reconstituted material for the ADVIA Centaur IgE MCMs to ensure that it maintains optimal product performance throughout the established shelf-life. The data supports the stability claims detailed in the ADVIA Centaur IgE MCM Instructions for Use.
The following stability studies were performed for ADVIA Centaur IgE MCM:
- Real Time/Shelf Life (unopened) Stability
- In Use Open Vial (reconstituted) stored at 2-8°C Stability ●
- On-Board Stability
Real time shelf-life studies (unopened): Test IgE MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 7 months, 8 months, 9 months, 11 months,12 months, 18 months, 35 months and 36 months. Shelf life claims are based upon real time stability carried out one month after the duration claimed. Real time shelf-life stability studies of MCMs were determined by comparison of dose recoveries at T=0. Current testing meets the sponsor's acceptance criteria for the real-time stability study up to the 9 months' time point, which supports a shelf-life claim of 8 months. Storage shelf-life (unopened) at 2-8°C is indicated by the expiration date on the vial label.
In-Use Open Vial (Reconstituted): Test IgE MCMs were reconstituted, each level pooled, aliquotted and stored at 2-8°C, tested in 5 replicates per level at T=0, 7, 14, 21, 28, and 29 days on the ADVIA Centaur XP system. Acceptance criteria for the open vial (reconstituted) stability study were met to the 29 days' time point, which supports the open vial claim of 28 days when properly stored at 2-8°C.
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On-board Stability: Pooled aliquots of test IgE MCMs in sample cups were stored on the ADVIA Centaur XP system and measured at time point T=0, 2, 4 and 5 hours. On-board stability studies of MCMs were determined by comparison of dose recoveries to the T=0 dose recovery results. Acceptance criteria for the on-board stability study were met up to 5 hours, which supports the on-board stability claim for 4 hours.
Stability Acceptance Criteria
The stability specifications acceptance criteria for the ADVIA Centaur IgE MCM are as follows:
- Real Time/Shelf life (Unopened): The dose recovery for MCM1 must be . ≤ 2.0 IU/mL dose; MCM2-7, the % dose recovery met the sponsor's required acceptance criteria.
- In-Use Open Vial (Reconstituted): The dose recovery for MCM1 must be < 2.0 IU/mL dose: MCM2-7, the % dose recovery met the sponsor's required acceptance criteria.
- On-Board: The dose recovery for MCM1 must be ≤ 2.0 IU/mL dose; . MCM2-7, the % dose recovery met the sponsor's required acceptance criteria.
9.2.2 Value Assignment
The ADVIA Centaur IgE MCMs are value assigned using assigned reference calibrators and MCMs. The assigned reference calibrators are prepared using IgE stock and are traceable to internal material which is standardized against World Health Organization (WHO) 75/502 reference material. The MCMs are manufactured using qualified materials and measurement procedures.
For each new IgE MCM lot manufactured, MCM1 is run in 5 replicates on two separate runs using one reagent kit lot on the ADVIA Centaur system. A nested testing run protocol is used for MCM2-MCM7 value assignment. This consists of running alternating samples of the reference and new MCM level in the same run. MCM2-MCM7 were tested on 20 replicates in total, comprised of one run and four sample cups run in 5 replicates on one system and one reagent kit lot. This protocol is designed to remove system and run variation. The new MCM doses must fall within the final value assignment specification for IgE MCMs. The MCMs dose values are generated using the two-point calibration. The new MCM dose is calculated based on the relationship between the observed reference MCM dose and its assigned value. A performance verification run consisting of 6 replicates of each MCM level is run using one instrument, one reagent kit lot and Bio-Rad controls. The mean MCM doses of the new MCM lot manufactured must fall within the customer range specifications.
The target for MCM1 is assigned a 0.0 dose. MCM1 is analyte-free basepool comprising of only the matrix and preservatives. The quality control specifications and final value assignment limits for IgE MCM ensure that MCM1 measures at or below the IgE assay sensitivity limit. MCM7 targeted greater than
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the assay range is diluted with the MCM1 to meet the reportable range of the assay.
9.2.3 Expected Values
The expected values are the lot-specific assigned values obtained at value assignment and the lot-specific assigned ranges are the lot-specific customer ranges are established per the sponsor's internal procedural specifications for IgE MCM.
ADVIA Centaur IgE MCM levels and target values are provided in Table 2.
| MCM level | Target Values(IU/mL) |
|---|---|
| MCM1 | 0.00 |
| MCM2 | 12.5 |
| MCM3 | 40.0 |
| MCM4 | 270 |
| MCM5 | 1000 |
| MCM6 | 1700 |
| MCM7 | 3150 |
| Assay Range | 1.5-3000 IU/mL |
Table 2: IgE MCM Levels and Target Values
9.2.4 Traceability
The ADVIA Centaur tIgE assay is standardized against the World Health Organization (WHO) 75/502. Assigned values for calibrators and MCMs are traceable to this standardization. Assigned values for calibrators and MCMs are traceable to this standardization. The IgE MCMs are manufactured using qualified materials and measurement procedures.
10. Proposed Labeling
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
11. Conclusion
The ADVIA Centaur IgE Master Curve Material (MCM) is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed IMMULITE 2000 Total IgE CVM. Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur IgE Master Curve 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.