(10 days)
For use in monitoring the performance of the Vitros ECi Immunodiagnostic System when used for the in vitro qualitative detection of Hepatitis B Surface Antigen (HBsAg) in human serum and plasma (EDTA, citrate and heparin). The performance of the Vitros Immunodiagnostic Products HBsAg Controls has not been established with any other HBsAg assays. For in vitro diagnostic use.
The Vitros Immunodiagnostic System uses luminescence as the signal in the qualitative detection of HBsAg in human plasma and serum. Coated microwells are used as the solid phase separation system. The system is compromised of three main elements: The Vitros Immunodiagnostic Products range of products, in this case Vitros Immunodiagnostic Products HBsAg Reagent Pack and Vitros Immunodiagnostic Products Calibrator; The Vitros Immunodiagnostic System- instrumentation; Common reagents used by the Vitros System in each assay, the Vitros Immunodiagnostic Products Signal Reagent and the Vitros Immunodiagnostic Products Universal Wash Reagent. The Vitros System and common reagents are dedicated specifically only for use with the Vitros Immunodiagnostic Products range of immunoassay products.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Vitros Immunodiagnostic Products HBsAg Controls:
This 510(k) summary (K030067) is for a quality control material (HBsAg Controls), not a diagnostic device that performs detection. Therefore, the typical "acceptance criteria" and "device performance" metrics for diagnostic accuracy (like sensitivity, specificity, AUC) are not directly applicable in the same way. Instead, the "performance" here refers to the ability of the control material to reliably monitor the performance of the associated diagnostic system (Vitros ECi Immunodiagnostic System).
The primary focus of this submission is an expansion of the intended use for the controls, specifically to include the monitoring of HBsAg detection in human plasma (EDTA, citrate, and heparin) in addition to serum. The original predicate device's controls were already approved for serum.
Given this context, the "acceptance criteria" relate to demonstrating that the controls perform equivalently across different sample matrices (serum vs. various plasma types).
1. Table of Acceptance Criteria and Reported Device Performance
Note: Specific quantitative acceptance criteria (e.g., "± X% variation") are not explicitly stated in the provided document for the control material's performance across different matrices. Instead, the document describes the demonstration that "all samples (serum, EDTA, citrate or heparin) behave similarly in the assay." This implies an acceptance criterion of comparable performance, but without specific numerical thresholds.
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Performance of controls in monitoring HBsAg assay is comparable across human serum, EDTA plasma, citrate plasma, and heparin plasma. | A technical report described the assessment where multiple samples (unspiked negative or spiked positive close to the weak positive detection level) were collected as whole serum or in the presence of EDTA, citrate, or heparin. The results showed that "all samples (serum, EDTA, citrate or heparin) behave similarly in the assay supporting that the controls can monitor the assay performance regardless of the tested sample matrix (serum or plasma)." This indicates the controls performed equivalently across these matrices. |
| Each control has a quoted mean value derived from a minimum of 10 assays and a standard deviation anticipated for single determinations of each control in a number of different laboratories using different reagent lots. Values are lot specific. | (This is a standing characteristic of both new and predicate controls, indicating how expected values are established. The document implies this method was applied to the new controls and found acceptable.) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document states "multiple samples collected as either whole serum or in the presence of EDTA citrate or heparin." A specific number for the test set sample size is not provided in this summary.
- Data Provenance: Not explicitly stated, but clinical laboratory in vitro diagnostic studies typically use banked or prospectively collected samples from a relevant patient population. No country of origin is mentioned. The study is described as an "assessment," suggesting it was likely a prospective or retrospective analysis of samples tested with the device.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This submission concerns the performance of quality control material for an HBsAg assay. The concept of "ground truth" established by experts (e.g., radiologists interpreting images) is not directly applicable here. The "truth" for the samples used in the study was determined by:
- Unspiked (negative) samples: Inherently negative for HBsAg.
- Spiked (positive) samples: Spiked with known positive HBsAg plasma, close to the weak positive detection level of the assay. This establishes their 'true positive' status for the purpose of the control's evaluation.
Therefore, no panel of independent experts was used to establish ground truth in the traditional sense for these control samples. The ground truth was defined by the sample preparation (negative or spiked positive).
4. Adjudication Method for the Test Set
Not applicable. As explained above, the "ground truth" was established by the design of the samples (unspiked negative or spiked positive), not by an expert adjudication process.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret results, often with and without AI assistance (e.g., radiology AI). The Vitros HBsAg Controls are quality control materials for an automated immunoassay system, not a device requiring human interpretation in this context.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
This question also doesn't directly apply. The "device" in question is a control material, not an algorithm, and the Vitros ECi Immunodiagnostic System itself is an automated system (algorithm-only in terms of result generation). The study described evaluated the control material's robustness across different sample matrices within the context of the automated system. It's an evaluation of the control's standalone performance in that respect, but not in the "algorithm-only vs. human-in-the-loop" sense.
7. The Type of Ground Truth Used
The ground truth used for the samples in the study was defined by the sample preparation:
- Known Negative: Unspiked samples were presumed negative.
- Known Positive (weak): Samples spiked with known HBsAg positive plasma to a level near the assay's weak positive detection threshold.
8. The Sample Size for the Training Set
- Not applicable directly. This submission is for a quality control material where performance is assessed through consistency and stability, not by training a machine learning algorithm. The "training set" concept is typically for AI/ML models.
- The quoted mean values and standard deviations for the controls are derived from "a minimum of 10 assays" in "a number of different laboratories using different reagent lots." This process, while not a "training set" in the AI sense, contributes to establishing the expected performance range of the controls.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As explained above, there is no "training set" in the context of an AI/ML model for this quality control material. The "ground truth" for the controls' expected values is established through repeated measurements (minimum of 10 assays) across various labs and reagent lots.
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General Information 2.0
JAN 1 7 2003
Confidential and Proprietary
510(k) Summary 2.1
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.
The assigned 510(k) number is: ______________
Submitter Name, Address, Contact 2.1.1
Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 (585) 453-3154
Contact Person: Sarah Parsons
2.1.2 Preparation Date
Date 510(k) Summary Prepared:
2.1.3 Device Name
Trade or Proprietary Name: Vitros Immunodiagnostic Products HBsAg Controls
HBsAg Controls Common Name:
Classification Name: 21CFR 862.1660 Quality Control Material (Assayed and Unassayed).
2.1.4 Predicate Device
The Vitros Immunodiagnostic Products HBsAg Controls are substantially equivalent to Ortho-Clinical Diagnostics, Inc. Vitros Immunodiagnostic Products HBsAg Controls (K011250).
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Device Description 2.1.5
The Vitros Immunodiagnostic System uses luminescence as the signal in the qualitative detection of HBsAg in human plasma and serum. Coated microwells are used as the solid phase separation system.
The system is compromised of three main elements:
- The Vitros Immunodiagnostic Products range of products, in this case 1. Vitros Immunodiagnostic Products HBsAg Reagent Pack and Vitros Immunodiagnostic Products Calibrator, which are combined by the Vitros Immunodiagnostic System to perform a Vitros assay. The Vitros Immunodiagnostic Products HBsAg Reagent Pack and Calibrator have been approved for sale (PMA P000044).
- The Vitros Immunodiagnostic System- instrumentation, which provides 2. automated use of the immunoassay kits. The Vitros Immunodiagnostic System was cleared be market by a separate 510(k) pre-market notification (K962919).
- Common reagents used by the Vitros System in each assay. The Vitros 3. Immunodiagnostic Products Signal Reagent and the Vitros Immunodiagnostic Products Universal Wash Reagent were cleared as part of the Vitros Immunodiagnostic Products Total T3 510(k) premarket notification (K964310).
The Vitros System and common reagents are dedicated specifically only for use with the Vitros Immunodiagnostic Products range of immunoassay products.
Device Intended Use 2.1.6
The Vitros Immunodiagnostic Products HBsAg Controls are intended for use in monitoring the performance of the Vitros ECi Immunodiagnostic System when used for the in vitro qualitative detection of Hepatitis B Surface Antigen (HBsAg) in human serum and plasma (EDTA, heparin or citrate). The performance of the Vitros Immunodiagnostic Products HBsAg Controls has not been established with any other HBsAg assays.
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Comparison to Predicate Device 2.1.7
The Vitros Immunodiagnostic Products HBsAg Controls are substantially equivalent to Ortho-Clinical Diagnostics Inc. Vitros Immunodiagnostic Products HBsAg Controls (K011250)
Table 1 lists the characteristics of the Vitros Immunodiagnostic Products HBsAg Controls (new device) and the Vitros Immunodiagnostic Products HBsAg Controls (predicate device).
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| DeviceCharacteristic | VitrosImmunodiagnosticProducts HBsAgControls(New device) | VitrosImmunodiagnosticProducts HBsAgControls(Predicate device) |
|---|---|---|
| Intended use | For use in monitoring theperformance of the VitrosECi ImmunodiagnosticSystem when used for thein vitro qualitativedetection of Hepatitis BSurface Antigen (HBsAg)in human serum andplasma (EDTA, citrateand heparin). Theperformance of the VitrosImmunodiagnosticProducts HBsAg Controlshas not been establishedwith any other HBsAgassays. | For use in monitoring theperformance of the VitrosECi ImmunodiagnosticSystem when used for thein vitro qualitativedetection of Hepatitis BSurface Antigen (HBsAg)in human serum. Theperformance of the VitrosImmunodiagnosticProducts HBsAg Controlshas not been establishedwith any other HBsAgassays. |
| Matrix of controls | Human serum with addedconstituents of humanorigin and antimicrobialagents | Human serum with addedconstituents of humanorigin and antimicrobialagents |
| Control level | Positive and negative | Positive and negative |
| Expected values | Each control has a quotedmean value derived froma minimum of 10 assaysand a standard deviationanticipated for singledeterminations of eachcontrol in a number ofdifferent laboratoriesusing different reagentlots. Values are lotspecific | Each control has a quotedmean value derived froma minimum of 10 assaysand a standard deviationanticipated for singledeterminations of eachcontrol in a number ofdifferent laboratoriesusing different reagentlots. Values are lotspecific |
Table 1. Comparison of New Device and Predicate Device
Summary of Assessment of Performance Data 2.1.8
The new device is the same as the predicate device with the addition of data that supports a modification in the Intended Use. Additional data demonstrate the use of the controls to assess the performance of the Vitros Immunodiagnostic Products HBsAg assay when determining the qualitative
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detection of HBsAg in human plasma (EDTA, citrate and heparin) in addition to serum. Included in this 510(k) submission is the technical report that describes the assessment of multiple samples collected as either whole serum or in the presence of EDTA citrate or heparin. Each sample was tested either unspiked (negative) or spiked with known positive HBsAg plasma close to the weak positive detection level of the assay (positive). The results showed that all samples (serum, EDTA, citrate or heparin) behave similarly in the assay supporting that the controls can monitor the assay performance regardless of the tested sample matrix (serum or plasma).
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Image /page/5/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of three human profiles facing right, arranged in a stacked formation. The profiles are simple and abstract, with smooth lines suggesting the shape of a head and face. The profiles are encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JAN 1 7 2003
Ms. Sarah Parsons Associate, Regulatory Affairs Ortho-Clinical Diagnostics. Inc. Regulatory Affairs MC00882 100 Indigo Creek Drive Rochester, NY 14626-5101
Re: K030067
Trade/Device Name: Vitros Immunodiagnostic Products HBsAg Controls Regulation Number: 21 CFR 862.1660 Regulation Name: Quality Control Material (Assayed and Unassayed). Regulatory Class: Class I Product Code: MJX Dated: January 6, 2003 Received: January 7, 2003
Dear Ms. Parsons:
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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Steven Putman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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3.0 SUMMARY INFORMATION
Statement of Intended Use 3.1
Page 1 of 1
KU 30067 510(k) Number (if known):
Vitros Immunodiagnostic Products HBsAg Controls
Indications for Use:
Device Name:
For use in monitoring the performance of the Vitros ECi Immunodiagnostic System when used for the in vitro qualitative detection of Hepatitis B Surface Antigen (HBsAg) in human serum and plasma (EDTA, citrate and heparin). The performance of the Vitros Immunodiagnostic Products HBsAg Controls has not been established with any other HBsAg assays.
For in vitro diagnostic use.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Freddie Lu. Poole
n of Clinical Laboratory Devices
510(k) Number K030067
Prescription Use
OR
Over-The-Counter Use _
Ortho-Clinical Diagnostics, Inc.
§ 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.