(66 days)
The ADVIA Centaur® Insulin (IRI) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur® Insuin assay.
The ADVIA Centaur® Insulin (IRI) Calibrator is for in vitro diagnostic use in calibrating the ADVIA Centaur® systems Insulin assays.
ADVIA Centaur® Insulin (IRI) Master Curve Material is a set of ten vials of material containing various levels of insulin in buffered saline with casein, potassium thiocyanate (3.89%), sodium azide (<0.1%), and preservatives. Each set contains ten levels (MCM1-10); ready-to-use 1.0 mL per level. MCM1 contains no analyte. The IRI MCMs assigned values are lot-specific of target values: 0.0, 2.5, 4.5, 10.0, 20.0, 39.0, 79.0, 158, 225, and 330 mU/L.
ADVIA Centaur® Insulin (IRI) Calibrator is a set of four vials (two vials of low calibrator and two vials of high calibrator) comprised of buffered saline, with casein, potassium thiocyanate, sodium azide and preservative. Only the high calibrator contains insulin.
The provided text describes modifications to the "ADVIA Centaur® Insulin (IRI) Master Curve Material (MCM)" and "ADVIA Centaur® Insulin (IRI) Calibrator" and outlines the studies conducted to demonstrate their substantial equivalence to predicate devices.
Here's an analysis of the acceptance criteria and the study information, extracting what is available:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state quantitative acceptance criteria in a table format with corresponding performance metrics for the modified devices. Instead, it states that "Verification testing was conducted and results show that the modified devices meet pre-determined acceptance criteria." and that a "method comparison study demonstrates that human clinical sample results are equivalent with both calibrators (modified and unmodified)."
However, based on the context, the implicit acceptance criteria and reported performance would be:
| Acceptance Criteria Category | Implicit Acceptance Criteria (based on "same" characteristics and equivalence claims) | Reported Device Performance (based on "same" characteristics and equivalence claims) |
|---|---|---|
| ADVIA Centaur® Insulin (IRI) Master Curve Material (MCM) | ||
| Intended Use | Same as predicate | Same as predicate |
| Instrument | Same as predicate (ADVIA Centaur Systems) | Same as predicate (ADVIA Centaur Systems) |
| Form | Same as predicate (Liquid) | Same as predicate (Liquid) |
| Matrix | Same as predicate (Buffered saline with casein, potassium thiocyanate, sodium azide and preservatives) | Same as predicate (Buffered saline with casein, potassium thiocyanate, sodium azide and preservatives) |
| Number of Levels | Same as predicate (10) | Same as predicate (10) |
| Target Concentrations | Same as predicate (0.0, 2.5, 4.5, 10.0, 20.0, 39.0, 79.0, 158, 225, 330 mU/L) | Same as predicate (0.0, 2.5, 4.5, 10.0, 20.0, 39.0, 79.0, 158, 225, 330 mU/L) |
| Fill Volume | Same as predicate (1.0 mL) | Same as predicate (1.0 mL) |
| Shelf Life/Stability | Same as predicate (12 months at 2-8 degrees C) | Same as predicate (12 months at 2-8 degrees C) |
| On board Stability | Same as predicate (8 hours on board) | Same as predicate (8 hours on board) |
| ADVIA Centaur® Insulin (IRI) Calibrator | ||
| Intended Use | Same as predicate | Same as predicate |
| Instrument | Same as predicate (ADVIA Centaur Systems) | Same as predicate (ADVIA Centaur Systems) |
| Form | Same as predicate (Liquid) | Same as predicate (Liquid) |
| Matrix | Same as predicate (Buffered saline with casein, potassium thiocyanate, sodium azide and preservatives) | Same as predicate (Buffered saline with casein, potassium thiocyanate, sodium azide and preservatives) |
| Number of Levels | Same as predicate (2) | Same as predicate (2) |
| Target Concentrations | Same as predicate (Low: <0.5 mU/L, 135 – 165 mU/L) | Same as predicate (Low: <0.5 mU/L, 135 – 165 mU/L) |
| Fill Volume | Same as predicate (1.0 mL) | Same as predicate (1.0 mL) |
| Shelf Life/Stability | Same as predicate (18 months at 2-8 degrees C) | Same as predicate (18 months at 2-8 degrees C) |
| On board Stability | Same as predicate (8 hours) | Same as predicate (8 hours) |
| Overall Performance | Equivalent human clinical sample results with modified and unmodified calibrators | Achieved equivalence in human clinical sample results. |
| Other | Meets pre-determined acceptance criteria for verification testing | Modified devices meet pre-determined acceptance criteria. |
2. Sample size used for the test set and the data provenance:
- Test set sample size: Not explicitly stated. The document mentions "human clinical sample results" were used in a method comparison study, but the number of samples is not provided.
- Data provenance: "human clinical sample results" are mentioned, suggesting human patient samples. The country of origin and whether the data is retrospective or prospective are not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided. The study concerns assay calibrators and master curve materials, where "ground truth" would typically refer to the accurately assigned values of the analytes in the calibrators/controls, usually established through highly accurate reference methods or certified reference materials, not expert human interpretation.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable in this context. Adjudication methods like 2+1 or 3+1 are typically used for studies involving human interpretation of images or clinical data, where consensus among experts establishes ground truth. This is a study of in-vitro diagnostic device performance (calibrators and master curve materials), not human interpretation.
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 not a study involving human readers or AI assistance.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The device is an in-vitro diagnostic calibrator/master curve material, not an algorithm. The performance evaluation is inherently "standalone" in the sense that the device itself is being tested for its ability to correctly verify calibration and calibrate assays. The study of "method comparison" compares the results obtained using the modified calibrators/materials versus the unmodified ones on human clinical samples, which is a standalone performance assessment of the materials.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The "ground truth" for the calibrator values and master curve material values is inherent in their design and manufacturing process, where specific concentrations of insulin are prepared and assigned. For the "method comparison study," the ground truth is implied to be the measurements obtained using the predicate (unmodified) calibrators/materials, with which the modified devices' performance is compared for equivalence. It's about demonstrating that measurements of "human clinical sample results" using the new materials are equivalent to those obtained using the established predicate materials.
8. The sample size for the training set:
Not applicable. This device is an in-vitro diagnostic calibrator/master curve material, not an AI/ML algorithm that requires a training set.
9. How the ground truth for the training set was established:
Not applicable, as there is no training set for this type of device.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
SIEMENS HEALTHCARE DIAGNOSTICS SUSAN FERRIN REGULATORY AFFAIRS CLINICAL SPECIALIST 333 CONEY STREET E. WALPOLE, MA 02032
November 17, 2016
Re: K162538
Trade/Device Name: ADVIA Centaur Insulin (IRI) Master Curve Material (MCM) ADVIA Centaur (IRI) Calibrator Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT, JJX Dated: October 17th, 2016 Received: October 18th, 2016
Dear Ms. Ferrin:
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,
Katherine Serrano -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
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Indications for Use
510(k) Number (if known) K162538
Device Name
ADVIA Centaur® Insulin (IRI) M aster Curve Material (MCM ) ADVIA Centaur® Insulin (IRI) Calibrator
Indications for Use (Describe)
The ADVIA Centaur® Insulin (IRI) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur® Insuin assay.
The ADVIA Centaur® Insulin (IRI) Calibrator is for in vitro diagnostic use in calibrating the ADVIA Centaur® systems Insulin assays.
| 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
A summary of information in accordance with 21 CFR 807.92 is provided below.
| The assigned 510(k) Number | K162538 |
|---|---|
| ---------------------------- | --------- |
| Applicant InformationMailing Address: | Siemens Healthcare Diagnostics Inc.333 Coney StreetEast Walpole, MA 02032 |
|---|---|
| Contact Person: | Susan Ferrin |
| Phone Number:Fax Number:E-mail Address:Date Prepared: | 508-660-4487508-660-4591susan.ferrin@siemens.comNovember 16, 2016 |
| Device InformationTrade/Proprietary Name | ADVIA Centaur® Insulin (IRI)Master Curve Material (MCM) | ADVIA Centaur® Insulin(IRI) Calibrator |
|---|---|---|
| Common/Usual Name | Assay verification material | Calibrator/normalizer |
| Regulation Section | 21 CFR 862.1660 | 21 CFR 862.1150 |
| Classification | Class I Reserved | Class II |
| Products Code | JJX – Single (Specified) AnalyteControls (Assayed and Unassayed) | JIT - Calibrator, Secondary |
| Panel | Clinical Chemistry (75) | Clinical Chemistry (75) |
| Predicate | ADVIA Centaur® Insulin (IRI)Master Curve Material (MCM) | ADVIA Centaur® Insulin (IRI)Calibrator |
| 510(k) No. | K142864 | K021535 |
| Device Description: | ADVIA Centaur® Insulin (IRI)Master Curve Material is a set often vials of material containingvarious levels of insulin inbuffered saline with casein,potassium thiocyanate (3.89%),sodium azide (<0.1%), andpreservatives. Each set containsten levels (MCM1-10); ready-to-use 1.0 mL per level. MCM1contains no analyte. The IRIMCMs assigned values are lot-specific of target values: 0.0, 2.5,4.5, 10.0, 20.0, 39.0, 79.0, 158,225, and 330 mU/L. | ADVIA Centaur® Insulin (IRI)Calibrator is a set of four vials(two vials of low calibratorand two vials of highcalibrator) comprised ofbuffered saline, with casein,potassium thiocyanate, sodiumazide and preservative. Onlythe high calibrator containsinsulin. |
| Intended Use and Indicationsfor Use | The ADVIA Centaur® Insulin(IRI) Master Curve Material is forin vitro diagnostic use in theverification of calibration andreportable range of the ADVIACentaur® Insulin assay. | The ADVIA Centaur® Insulin(IRI) Calibrator is for in vitrodiagnostic use in calibratingthe ADVIA Centaur® systemsInsulin assays. |
| Special Conditions for UseStatement(s) | For prescription use only | None |
| Instrument Requirements: | ADVIA Centaur® SystemsA description of the ADVIACentaur® system is documented inK971418. Subsequentmodifications to the instrumenthave been reviewed and clearedin K032525 and K041133. | ADVIA Centaur® SystemsA description of the ADVIACentaur® system isdocumented in K971418.Subsequent modifications tothe instrument have beenreviewed and cleared inK032525 and K041133. |
| Comparison of TechnologicalCharacteristics: | Summarized in Table 1 below. | Summarized in Table 2 below. |
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SIEMENS
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Table 1: ADVIA Centaur® Insulin (IRI) Master Curve Material
| Characteristic | Candidate Device -ADVIA Centaur® InsulinMaster Curve Material (MCM) | Cleared Device -ADVIA Centaur® Insulin MasterCurve Material (MCM) |
|---|---|---|
| Intended Use | Same | The ADVIA Centaur® Insulin (IRI) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Insulin assay. |
| Instrument | Same | ADVIA Centaur Systems |
| Form | Same | Liquid |
| Matrix | Same | Buffered saline with casein, postassium thiocyanate, sodium azide and preservatives |
| Ingredient | Human Insulin (porcine sourced) | Human Insulin (human sourced) |
| Number of Levels | Same | 10 |
| TargetConcentrations | Same | 0.0, 2.5, 4.5, 10.0, 20.0, 39.0, 79.0, 158, 225, 330 mU/L |
| Fill Volume | Same | 1.0 mL |
| Shelf Life/Stability | Same | 12 months at 2-8 degrees C |
| On board Stability | Same | 8 hours on board |
Table 2: ADVIA Centaur® Insulin (IRI) Calibrator
| Characteristic | Candidate DeviceADVIA Centaur® InsulinCalibrator | Predicate DeviceADVIA Centaur® Insulin Calibrator |
|---|---|---|
| Intended Use | Same | The ADVIA Centaur® Insulin (IRI)Calibrator is for in vitro diagnostic usein calibrating the ADVIA Centaur®systems Insulin assays. |
| Instrument | Same | ADVIA Centaur Systems |
| Form | Same | Liquid |
| Matrix | Same | Buffered saline with casein, potassiumthiocyanate, sodium azide andpreservatives |
| Ingredient | Human Insulin (porcine sourced) | Human Insulin (human sourced) |
| Number of Levels | Same | 2 |
| TargetConcentrations | Same | Low: <0.5 mU/L135 – 165 mU/L |
| Fill Volume | Same | 1.0 mL |
| Shelf Life/Stability | Same | 18 months at 2-8 degrees C |
| On board Stability | Same | 8 hours |
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SIEMENS
Summary of Design Control Activities
The procedure for risk management activities is based on ISO 14971 (2007), Medical Devices -Application of Risk Management to Medical Devices and the risk analysis method used to assess the impact of the device modification was a Failure Modes and Effects Analysis. The following performance characteristics of the devices were considered for potential hazards: Shelf Life (closed vial) and Shelf Life (onboard). Verification testing was conducted and results show that the modified devices meet pre-determined acceptance criteria. Additionally, a method comparison study demonstrates that human clinical sample results are equivalent with both calibrators (modified and unmodified) using different antigen sources (human and porcine). The modification does not negatively impact the performance of the devices or the safety and effectiveness of the devices.
Conclusion
The modified ADVIA Centaur® Insulin (IRI) Master Curve Material (MCM) and ADVIA Centaur® Insulin (IRI) Calibrator devices are substantially equivalent to the currently marketed ADVIA Centaur® Insulin (IRI) Master Curve Material (MCM) and ADVIA Centaur® Insulin (IRI) Calibrator. Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur® Insulin (IRI) Master Curve Material (MCM) and ADVIA Centaur® Insulin (IRI) Calibrator devices do not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.
§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.