(22 days)
For the in vitro quantitative measurement of myoglobin concentration in human serum or plasma (EDTA or heparin) to aid in the diagnosis of myocardial infarction.
For in vitro use in the calibration of the Vitros Immunodiagnostic System for the quantitative measurement of Myoglobin in human serum and plasma (EDTA or heparin).
Assayed for use in verifying the calibration range of the Vitros Immunodiagnostic System when used for the measurement of Myoglobin. For in vitro use.
The Vitros Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system.
The system is comprised of three main elements:
-
- The Vitros Immunodiagnostic Products range of immunoassay products: Vitros Immunodiagnostic Products Myoglobin Reagent Pack, the Vitros Immunodiagnostic Products Myoglobin Calibrators and the Vitros Immunodiagnostic Products Myoglobin Range Verifiers, (which are combined by the Vitros Immunodiagnostic System to perform the Vitros Myoglobin assay), and Vitros Immunodiagnostic Products High Sample Diluent B.
-
- The Vitros Immunodiagnostic System -- instrumentation, which provides automated use of the immunoassay kits.
-
- Common reagents used by the Vitros System in each assay.
The Vitros System and common reagents are dedicated specifically for use only with the Vitros Immunodiagnostic Products range of immunoassay products.
The provided text describes the 510(k) summary for the Vitros Immunodiagnostic Products Myoglobin Reagent Pack, Calibrators, and Range Verifiers. This is an in vitro diagnostic (IVD) device, and the information typically required for an AI/ML SaMD acceptance criteria study (e.g., sample size for test set, number of experts, adjudication method) does not directly apply in the same way.
However, I can extract information related to the device's performance compared to a predicate device, which serves a similar purpose in demonstrating functional equivalence.
Here's an analysis based on the provided text, adapted for IVD devices:
Acceptance Criteria and Study for Vitros Immunodiagnostic Products Myoglobin Assay
The Vitros Immunodiagnostic Products Myoglobin Reagent Pack, Calibrators, and Range Verifiers were shown to be substantially equivalent to predicate devices through various analytical studies. The primary goal was to demonstrate comparable characteristics and performance to legally marketed devices.
1. Table of Acceptance Criteria and Reported Device Performance
For IVD devices, "acceptance criteria" for demonstrating substantial equivalence often involve comparisons of analytical performance characteristics (e.g., calibration range, precision, correlation) with a predicate device.
| Characteristic | Acceptance Criteria (Predicate Device) | Reported Device Performance (Vitros Myoglobin Assay) |
|---|---|---|
| Reagent Pack & Calibrators: | ||
| Calibration range | 0-1000 ng/mL (DADE Dimension RxL Myoglobin) | 0-2000 ng/mL (Vitros Myoglobin assay) |
| Basic principle | Solid phase immunoassay (DADE Dimension RxL Myoglobin) | Solid phase immunoassay (Vitros Myoglobin assay) |
| Tracer | Enzyme labeled (DADE Dimension RxL Myoglobin) | Enzyme labeled (Vitros Myoglobin assay) |
| Instrumentation | DADE Dimension Immunoassay System | Vitros Immunodiagnostic System |
| Antibody | Mouse monoclonal anti-myoglobin antibodies | Mouse monoclonal anti-myoglobin antibodies |
| Sample type | Serum and plasma (heparin) | Serum and plasma (EDTA or heparin) |
| Sample volume | 20μL | 10μL |
| Incubation time and temperature | 7 minutes at 37°C | 8 minutes at 37°C |
| Correlation to Predicate | Not explicitly stated as a strict acceptance criterion in the summary, but a correlation coefficient close to 1 and a slope close to 1 with minimal bias are generally expected for substantial equivalence. | Vitros Myoglobin = 0.990 x X + 0.81 (ng/mL), with a correlation coefficient of 0.997 (where X is DADE Dimension RxL Myoglobin Method). |
| Other performance characteristics | (Implied to be comparable) | Precision, analytical sensitivity, specificity, and expected values studies were performed (details in package insert). |
| Range Verifiers: | ||
| Intended Use | Verifying calibration range for cardiac Troponin I | Verifying calibration range for Myoglobin |
| Matrix | Freeze-dried human serum spiked with human analyte | Freeze-dried horse serum spiked with human analyte |
| Levels | Low and High | Low and High |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: The text states, "This relationship was determined from a panel of patient samples from a variety of clinical categories." A specific number for this panel is not provided within the summary.
- Data Provenance: The origin (e.g., country) of the patient samples or whether they were retrospective or prospective is not specified in the provided summary.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This is not applicable to this type of IVD device submission. The "ground truth" for an assay is typically established through a reference method or target values assigned to calibrators, not through expert consensus on medical images or clinical judgment. The DADE Dimension RxL Myoglobin Method acts as the reference for comparison studies.
4. Adjudication Method for the Test Set
This is not applicable as the "test set" here refers to patient samples analyzed by two different diagnostic assays for comparison, not a set of cases requiring adjudication by human readers.
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
This is not applicable. This device is an immunoassay, not an AI/ML-driven diagnostic imaging or clinical decision support tool that involves human readers interpreting AI output.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This is applicable in the sense that the device's performance as an assay system (analyzer + reagents) was evaluated independently and then compared to the predicate device. The correlation study directly assesses the "standalone" analytical performance of the new Vitros Myoglobin assay compared to the predicate. The reported correlation coefficient of 0.997 and the regression equation demonstrate this standalone analytical performance.
7. The Type of Ground Truth Used
The "ground truth" was established by the results from the predicate device (DADE Dimension RxL Myoglobin Method) when analyzing the same patient samples. This is a common method for demonstrating substantial equivalence for new IVD assays by comparing them to an already cleared and accepted method. Additional studies on precision, analytical sensitivity, specificity, and expected values provide further grounding for the assay's performance characteristics.
8. The Sample Size for the Training Set
This is not applicable. Immunoassays are not "trained" in the same way AI/ML algorithms are. There isn't a defined training set in the context of machine learning. The assay's analytical characteristics are developed and verified through chemical and biological experimentation, calibration, and validation with various samples (including spiked samples, proficiency samples, and patient samples).
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no "training set" in the AI/ML sense for this type of device. The accuracy of the assay is established through its analytical and clinical performance studies, often referencing established methodologies or certified reference materials.
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NOV - 5 2003
Chapter 1 - Summary Information
510(k) Summary
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: K033300
| 1. Submitter name, address, contact | Ortho-Clinical Diagnostics, Inc.100 Indigo Creek DriveRochester, New York 14626-5101(585) 453-3730 |
|---|---|
| Contact Person: | Charlotte Baker |
| 2. Preparation date | Date 510(k) prepared: October 10, 2003 |
|---|---|
| --------------------- | ---------------------------------------- |
| 3. Device name | Trade or Proprietary Name:Vitros Immunodiagnostic Products Myoglobin Reagent PackVitros Immunodiagnostic Products Myoglobin CalibratorsVitros Immunodiagnostic Products Myoglobin Range VerifiersCommon Name: Myoglobin assayClassification Name: Immunoassay Method, Myoglobin (866.5680)Class: II |
|---|---|
| ---------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
| 4. Predicate device | a. The Vitros Immunodiagnostic Products Myoglobin assay is substantially equivalent to the DADE Dimension RxL Myoglobin (MYO) Method.b. The Vitros Immunodiagnostic Products Myoglobin Range Verifiers are substantially equivalent to the Vitros Troponin I Range Verifiers. |
|---|---|
| --------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
Continued on next page
{1}------------------------------------------------
The Vitros Immunodiagnostic System uses luminescence as the signal in the 5. Device quantitative and semi-quantitative determination of selected analytes in description human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system.
The system is comprised of three main elements:
-
- The Vitros Immunodiagnostic Products range of immunoassay products: Vitros Immunodiagnostic Products Myoglobin Reagent Pack, the Vitros Immunodiagnostic Products Myoglobin Calibrators and the Vitros Immunodiagnostic Products Myoglobin Range Verifiers, (which are combined by the Vitros Immunodiagnostic System to perform the Vitros Myoglobin assay), and Vitros Immunodiagnostic Products High Sample Diluent B.
Note: High Sample Diluent B was cleared as part of the Vitros Immunodiagnostic Products Total B-hCG Reagent Pack and Vitros Immunodiagnostic Products Total β-hCG Calibrators 510(k) premarket notification (K970894).
- The Vitros Immunodiagnostic Products range of immunoassay products: Vitros Immunodiagnostic Products Myoglobin Reagent Pack, the Vitros Immunodiagnostic Products Myoglobin Calibrators and the Vitros Immunodiagnostic Products Myoglobin Range Verifiers, (which are combined by the Vitros Immunodiagnostic System to perform the Vitros Myoglobin assay), and Vitros Immunodiagnostic Products High Sample Diluent B.
-
- The Vitros Immunodiagnostic System -- instrumentation, which provides automated use of the immunoassay kits. The Vitros Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
-
- Common reagents used by the Vitros System in each assay. The Vitros Immunodiagnostic Products Signal Reagent and Vitros Immunodiagnostic Products Universal Wash Reagent were cleared as part of the Vitros Immunodiagnostic Products Total T3 Reagent Pack and Vitros Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).
The Vitros System and common reagents are dedicated specifically for use only with the Vitros Immunodiagnostic Products range of immunoassay products.
Continued on next page
Ortho-Clinical Diagnostics, Inc.
Vitros Immunodiagnostic Products Myoglobin Reagent Pack Vitros Immunodiagnostic Products Myoglobin Calibrators Vitros Immunodiagnostic Products Myoglobin Range Verifiers Page 5 of 126
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a. The Vitros Myoglobin assay is intended for the in vitro quantitative 6. Device measurement of myoglobin concentration in human serum or plasma (EDTA, intended use or heparin) to aid in the diagnosis of myocardial infarction. b. The Vitros Myoglobin Range Verifiers are intended for the assayed use in verifying the calibration range of the Vitros Immunodiagnostic System when used for the measurement of Myoglobin. For in vitro use. The Vitros Immunodiagnostic Products Myoglobin Reagent Pack and Vitros 7. a. Comparison to Immunodiagnostic Products Myoglobin Calibrators are substantially predicate device: equivalent to the DADE Dimension RxL Myoglobin (MYO) Method Reagent Pack and (predicate device) which was cleared by the FDA (K984191) for IVD use. Calibrators The relationship between the Vitros Myoglobin and the predicate device, determined by Passing & Bablok, is: Vitros Myoglobin = 0.990 x X +0.81 (ng/mL), with a correlation coefficient of 0.997, where X is DADE Dimension RxL Myoglobin Method. This relationship was determined from a panel of patient samples from a variety of clinical categories. In addition to the above mentioned correlation studies were performed to determine the precision, analytical sensitivity, specificity and expected values of the Vitros Myoglobin assay, (refer to the Vitros Myoglobin Reagent package insert for summaries of the results of these studies). Table 1 lists the characteristics of the assays performed using the Vitros Myoglobin assay and the DADE Dimension RxL Myoglobin (MYO) assay. Continued on next page
Ortho-Clinical Diagnostics, Inc.
{3}------------------------------------------------
| 7. a.Comparison topredicate | Table 1DeviceCharacteristic | New Device | Predicate Device |
|---|---|---|---|
| device: Reagent | Calibration range | 0-2000 ng/mL | 0-1000 ng/mL |
| Pack andCalibrators,Continued | Basic principle | Solid phaseimmunoassay | Solid phaseimmunoassay |
| Tracer | Enzyme labeled | Enzyme labeled | |
| Instrumentation | VitrosImmunodiagnosticSystem | DADE DimensionImmunoassay System | |
| Antibody | Mouse monoclonal anti-myoglobin antibodies | Mouse monoclonal anti-myoglobin antibodies | |
| Sample type | Serum and plasma(EDTA or heparin) | Serum and plasma(heparin) | |
| Sample volume | 10μL | 20μL | |
| Incubation time andtemperature | 8 minutes at 37°C | 7 minutes at 37°C |
- b. Comparison to predicate device: Range Verifiers
The Vitros Immunodiagnostic Products Myoglobin Range Verifiers are substantially equivalent to the Vitros Troponin I Range Verifiers (predicate device) which was cleared by the FDA (K992349) for IVD use.
Table 2 lists the similarities and differences of the device characteristics between the Vitros Myoglobin Range Verifiers with the predicate device, Vitros Troponin I Range Verifiers.
| Table 2 | ||
|---|---|---|
| Characteristics | New Device | Predicate Device |
| Intended Use | Assayed for use in verifying thecalibration range of the VitrosImmunodiagnostic System whenused for the measurement ofMyoglobin. For in vitro use. | Assayed for use in verifying thecalibration range of the VitrosImmunodiagnostic System when usedfor the measurement of cardiacTroponin I (cTnI). For in vitro use. |
| Matrix of RangeVerifiers | A base matrix of freeze-dried horseserum spiked with analyte of humanorigin | A base matrix of freeze-dried humanserum spiked with analyte of humanorigin. |
| Range VerifierLevels | Low and High | Low and High |
Ortho-Clinical Diagnostics, Inc.
Vitros Immunodiagnostic Products Myoglobin Reagent Pack Vitros Immunodiagnostic Products Myoglobin Calibrators Vitros Immunodiagnostic Products Myoglobin Range Verifiers
{4}------------------------------------------------
8. Conclusions
| a. Reagent Packand Calibrators: | Equivalence was demonstrated using currently commercially availablereagents along with patient samples by comparing the physical propertiesand intended uses of these devices with commercially available reagents. |
|---|---|
| b. Range Verifiers: | Both the new device and the predicate device are intended for the assayeduse in verifying the calibration range of immunoassays determined byimmunoassay analyzers. The new device and predicate device aresubstantially equivalent. |
| The data presented in the premarket notification provide a reasonableassurance that the Vitros Myoglobin assay and the Vitros MyoglobinRange Verifiers are safe and effective for the stated intended uses and aresubstantially equivalent to the cleared predicate devices. |
Vitros Immunodiagnostic Products Myoglobin Reagent Pack Vitros Immunodiagnostic Products Myoglobin Calibrators Vitros Immunodiagnostic Products Myoglobin Range Verifiers
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features an abstract image of an eagle with three stripes representing the department's mission. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.
NOV - 5 2003
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Charlotte Baker Regulatory Affairs Associate Ortho-Clinic Diagnostics, Inc. Regulatory Affairs MC00881 100 Indigo Creek Drive Rochester, NY 14626-5101
K033300 Re:
Trade/Device Name: Virtos Immunodiagnostic Products Myoglobin Reagent Pack Virtos Immunodiagnostic Products Myoglobin Calibrators Virtos Immunodiagnostic Products Myoglobin Range Verifiers Regulation Number: 21 CFR 866.5680 Regulation Name: Myoglobin immunological test system Regulatory Class: Class II Product Code: DDR; JIS; JJX Dated: October 10, 2003 Received: October 14, 2003
Dear Ms. Baker:
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). You may obtain other general information on your responsibilities under the Act 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
{7}------------------------------------------------
Indications for Use Statement
| 510(k) Number (if known): | K033300 |
|---|---|
| Device Name: | Vitros Immunodiagnostic Products Myoglobin Reagent PackVitros Immunodiagnostic Products Myoglobin CalibratorsVitros Immunodiagnostic Products Myoglobin Range Verifiers |
| Indications for Use: | For the in vitro quantitative measurement of myoglobinconcentration in human serum or plasma (EDTA or heparin) toaid in the diagnosis of myocardial infarction.For in vitro use in the calibration of the VitrosImmunodiagnostic System for the quantitative measurement ofMyoglobin in human serum and plasma (EDTA or heparin).Assayed for use in verifying the calibration range of the VitrosImmunodiagnostic System when used for the measurement ofMyoglobin. For in vitro use. |
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
| Prescription Use (Per 21 CFR 801.109) | |
|---|---|
| --------------------------------------- | ------------------------------------------------------------------ |
OR
| Over-The-Counter Use | |
|---|---|
| ---------------------- | -- |
| Division Sign-Off | Carol Benson |
|---|---|
| B. Jean Cooper, DVM |
(Optional Format 1-2-96)
Office of In Vitro Diagnostic Device Evaluation and Safety
| 510(k) | K033300 |
|---|---|
| -------- | --------- |
Ortho-Clinical Diagnostics, Inc.
Vitros Immunodiagnostic Products Myoglobin Reagent Pack Vitros Immunodiagnostic Products Myoglobin Calibrators Vitros Immunodiagnostic Products Myoglobin Range Verifiers Page 10 of 126
§ 866.5680 Myoglobin immunological test system.
(a)
Identification. A myoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.(b)
Classification. Class II (performance standards).