(25 days)
For in vitro diagnostic use only.
For use in the calibration of the VITROS ECVECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System for the quantitative measurement of insulin in human serum and plasma (Li Heparin).
The VITROS® Immunodiagnostic Products Insulin Calibrators contain three levels of calibrator, Calibrator 1, 2, 3. Nominal values are 1 uIU/mL, 25 µIU/mL and 250 µIU/mL respectively. The calibrators are liquid and comprised of recombinant human insulin in buffer containing BSA with an antimicrobial agent. VITROS® Immunodiagnostic Products Insulin Calibrators kit contains 1 vial of each calibrator 1, 2, and 3. Each vial contains 1mL of calibrator.
This document is a 510(k) Premarket Notification from Ortho-Clinical Diagnostics, Inc. to the FDA regarding their VITROS® Immunodiagnostic Products Insulin Calibrators. It aims to demonstrate substantial equivalence to a legally marketed predicate device.
Based on the provided text, the device in question is a calibrator for in vitro diagnostic use, not an AI-powered medical device for image analysis or disease detection. Therefore, the questions related to AI performance metrics (like sensitivity, specificity, MRMC studies, human reader improvement with AI assistance, ground truth establishment for AI training sets, etc.) are not applicable to this submission.
The acceptance criteria and performance data for this type of device (a calibrator) typically revolve around analytical performance characteristics such as:
- Stability: How long the calibrator remains effective under different storage conditions (unopened shelf-life, opened on-board stability).
- Traceability: Ensuring the values assigned to the calibrators are linked to a recognized international standard.
- Value Assignment: The process by which the calibrator values are accurately determined.
Here's how the provided document addresses these aspects:
1. A table of acceptance criteria and the reported device performance
The document does not present a formal table of acceptance criteria with corresponding performance results in the way one would for an AI-powered diagnostic device (e.g., sensitivity/specificity targets). Instead, it discusses the studies and principles related to the calibrator's performance.
Acceptance Criteria (Implied for a Calibrator):
- Shelf-life: The calibrators must maintain their stated values and functionality for a specific duration when stored unopened.
- Opened Stability: The calibrators must maintain their stated values and functionality for a specific duration after being opened and placed on the instrument.
- Traceability: The assigned values must be traceable to an internationally recognized standard.
- Value Assignment Accuracy: The process for assigning values must be robust and accurate, ensuring reliable calibration curves.
Reported Device Performance (as described in the text):
- Unopened Stability: "Shelf-life of the VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study. The final shelf life claim will be based on the completed real time study results." (This indicates a study is ongoing/planned to establish the shelf-life, not that a final claim is being made in this report).
- Opened Stability: "Storage life for open vials of VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study and will support the open off board shelf life statement in the Instructions for Use." (Similar to unopened stability, the study is planned/ongoing).
- Traceability: "Values assigned to the VITROS Immunodiagnostic Products Insulin Calibrators are traceable to the WHO 1st International Reference Preparation 66/304."
- Value Assignment: "The Value assignment process transfers the calibration from the WHO Standard (66/304) to reference standards and then to calibrators used by the end user to establish a valid calibration curve on the VITROS ECi/ECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System."
Summary of Stability (from page 6):
- Unopened: "Store at 2-8°C until expiration date"
- Opened: "13 weeks"
- Note: This appears in the "Comparison with Predicate - Differences" table (page 5), suggesting these are the claims for the new device, and the "Summary of Stability" on page 6 refers to the studies being conducted to support these claims, or previous studies that led to these claims. For the predicate device, opened stability is "Store at 2-8°C until expiration date."
2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
The term "test set" in the context of AI models is not directly applicable here. For a calibrator, the "test set" would typically refer to the samples used in stability studies. The document states:
- "Shelf-life of the VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study."
- "Storage life for open vials of VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study."
Details on the sample sizes (e.g., number of calibrator lots, number of measurements per time point) or data provenance (country of origin) for these stability studies are not provided in this summary. The studies are described as "real time," indicating they are prospective studies.
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)
As this is a calibrator, "ground truth" is established via traceability to an internationally recognized reference preparation, not through human expert interpretation. The document states:
- "Values assigned to the VITROS Immunodiagnostic Products Insulin Calibrators are traceable to the WHO 1st International Reference Preparation 66/304."
Therefore, human experts are not applicable for establishing "ground truth" in this context.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
Not applicable. Adjudication methods are used in studies involving human interpretation or challenging diagnostic cases. For a calibrator, performance is assessed through analytical measurements and traceability, not through 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 device is a calibrator, not an AI-powered diagnostic tool, and involves no human readers or image interpretation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This device is a physical calibrator reagent, not an algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the calibrator's value assignment is based on traceability to a recognized international reference standard: "WHO 1st International Reference Preparation 66/304." This is a metrological ground truth for analytical measurement.
8. The sample size for the training set
Not applicable. As this is a calibrator for in vitro diagnostics, not a machine learning model, there is no "training set" in the AI sense. Calibration involves a direct measurement comparison against a reference, not a data-driven learning process.
9. How the ground truth for the training set was established
Not applicable. See point 8.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 16, 2017
ORTHO-CLINICAL DIAGNOSTICS, INC. BRADLEY P. BOYER SENIOR REGULATORY ASSOCIATE 100 INDIGO CREEK DRIVE ROCHESTER NY 14626
Re: K171168
Trade/Device Name: VITROS Immunodiagnostic Products Insulin Calibrators Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: April 20, 2017 Received: April 21, 2017
Dear Bradley P. Boyer:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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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,
Kellie B. Kelm -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) K171168
Device Name
VITROS® Immunodiagnostic Products Insulin Calibrators
Indications for Use (Describe) For in vitro diagnostic use only.
For use in the calibration of the VITROS ECVECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System for the quantitative measurement of insulin in human serum and plasma (Li Heparin).
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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510(k) Summary of Safety and Effectiveness for the VITROS® Immunodiagnostic Products Insulin Calibrators
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
1. 510(k) Number:
The assigned 510(k) number is: K171168
2. Applicant
| Contact Person: | Bradley P. Boyer |
|---|---|
| Senior Regulatory Associate | |
| Address: | Ortho-Clinical Diagnostics, Inc. |
| 100 Indigo Creek Drive | |
| Rochester, New York 14626-5101 | |
| Phone: | (585) 453-3421 |
| Facsimile: | (585) 453-3368 |
| Email: | bradley.boyer@orthoclinicaldiagnostics.com |
3. Date April 20, 2017
4. Device Name
Trade or Proprietary Names: VITROS® Immunodiagnostic Products Insulin Calibrators
Common Names:
Insulin Calibrators
5. Regulatory Information
Regulation section: 21 CFR 862.1150; calibrator, secondary Classification Class II Product Code: JIT Panel: Clinical Chemistry
6. Predicate Device
| Device Name | Architect Insulin Calibrators |
|---|---|
| 510(k) number: | K060359 |
| Manufacturer: | Produced for Abbott by Denka Seiken Co., Ltd. |
7. Intended Use
See Indications for Use
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8. Indications for Use VITROS® Immunodiagnostic Products Insulin Calibrators
VITROS Immunodiagnostic Products Insulin Calibr
For in vitro diagnostic use only.
For use in the calibration of the VITROS ECi/ECiO Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System for the quantitative measurement of insulin in human serum and plasma (Li Heparin).
Special Conditions for use statement: For prescription use
9. Device Description
Calibrator description
The VITROS® Immunodiagnostic Products Insulin Calibrators contain three levels of calibrator, Calibrator 1, 2, 3. Nominal values are 1 uIU/mL, 25 µIU/mL and 250 µIU/mL respectively. The calibrators are liquid and comprised of recombinant human insulin in buffer containing BSA with an antimicrobial agent. VITROS® Immunodiagnostic Products Insulin Calibrators kit contains 1 vial of each calibrator 1, 2, and 3. Each vial contains 1mL of calibrator.
10. Test Principle:
VITROS® Immunodiagnostic Products Insulin Calibrators are intended for in vitro diagnostic use in the calibration of the VITROS Immunodiagnostic Products Insulin test on VITROS ECi/ECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System.
11. Substantial Equivalence Information:
VITROS® Immunodiagnostic Products Insulin Calibrators are substantially equivalent to predicate device Architect Insulin Calibrators (K060359) which was cleared by FDA for IVD use.
Comparison with predicate tables highlight similarities and differences, respectively, of the VITROS® Immunodiagnostic Products Insulin Calibrators as compared to the predicate device.
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| DeviceCharacteristic | VITROS® ImmunodiagnosticProducts Insulin Calibrators(New device) | K060359(Architect Insulin Calibrators) |
|---|---|---|
| Intended Use | For use in the calibration of theVITROS ECi/ECiQImmunodiagnostic Systems, theVITROS 3600 ImmunodiagnosticSystem and the VITROS 5600Integrated System for thequantitative measurement of insulinin human serum and plasma (LiHeparin). | The Architect Insulin Calibratorsare for the calibration of theArchitect i System when used forthe quantitative determination ofhuman insulin in human serum orplasma |
| Measured Analyte | Insulin | same |
| Form | Liquid | same |
| Traceability | WHO 1st International ReferencePreparation 66/304 | same |
| Assay Protocol | Direct, quantitative immunoassay | same |
Comparison with Predicate - Similarities
Comparison with Predicate - Differences
| DeviceCharacteristic | VITROS® ImmunodiagnosticProducts Insulin Calibrators(New device) | K060359(Architect Insulin Calibrators) |
|---|---|---|
| Instrumentation | VITROS® ECi/ECiQImmunodiagnostic Systems,VITROS® 3600Immunodiagnostic System and theVITROS® 5600 Integrated System | Architect i System |
| Concentration /Levels | 3 levels: 1, 25, 250 µIU/mL | Calibrators A-F.Cal A is acetate buffer, B-F arelevels: 0, 3, 10, 30, 100 µU/mL |
| Matrix | Buffer containing BSA andantimicrobial agent | Acetate buffer with sodium azideand preservatives |
| Stability | UnopenedStore at 2-8°C until expiration dateOpened13 weeks | UnopenedStore at 2-8°C until expiration dateOpenedStore at 2-8°C until expiration date |
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12. Standard/Guidance Document Reference
The following recognized standard and guidance documents were used: CLSI EP25-A – Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline Sept 2009.
CDRH Guidance for Industry: Abbreviated 510(k) Submissions for In Vitro Diagnostic Calibrators, issued on February 22, 1999,
13. Performance Characteristics
The following studies are not applicable for the purpose of this submission:
- Precision/Reproducibility .
- Linearity/Assay Reportable Range ●
- Detection limit ●
- Method and Matrix Comparison Studies ●
- Analytical Specificity
- Assay cut-off
- Expected Values/Reference Interval ●
Summary of Stability
Shelf-life of the VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study. The stability study is designed to determine shelflife for calibrators. The final shelf life claim will be based on the completed real time study results.
Storage life for open vials of VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study and will support the open off board shelf life statement in the Instructions for Use.
Summary of Traceability and Value assignment
Values assigned to the VITROS Immunodiagnostic Products Insulin Calibrators are traceable to the WHO 1st International Reference Preparation 66/304.
The Value assignment process transfers the calibration from the WHO Standard (66/304) to reference standards and then to calibrators used by the end user to establish a valid calibration curve on the VITROS ECi/ECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System.
14. Conclusion
Based on the comparison with the predicate device, the VITROS Immunodiagnostic Products Insulin Calibrators are substantially equivalent to the Architect Insulin Calibrators (K060359) cleared by FDA for IVD use.
§ 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.