(179 days)
The Diazyme Myoglobin Assay is for the quantitative determination of myoglobin in human serum and plasma. Measurement of myoglobin is used as an aid in the diagnosis of acute myocardial infarction. For in vitro diagnostic use only.
The Diazyme Myoglobin Calibrator Set is intended for use in the calibration of the Diazyme Myoglobin Assay. For in vitro diagnostic use only.
The Diazyme Myoglobin Control Set is intended for use as quality controls for the Diazyme Myoglobin Assay. For in vitro diagnostic use only.
The Diazyme Myoglobin Assay is based on a latex enhanced immunoturbidimetric assay. When an antigen-antibody reaction occurs between myoglobin in a sample and anti-myoglobin antibodies which have been sensitized to latex particles, agglutination occurs. This agglutination is detected as an absorbance change (570 nm), with the magnitude of the change being proportional to the quantity of myoglobin in the sample. The actual concentration is then determined by the interpolation from a calibration curve prepared from calibrators of known concentration.
The Diazyme Myoglobin Assay's acceptance criteria and performance are detailed across sections of the provided document. The study primarily relies on method comparison and precision evaluations to demonstrate substantial equivalence to a predicate device.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Method Comparison | High correlation (R² close to 1) and a slope close to 1 with an intercept close to 0 when compared to the predicate device. | R² = 0.9855, Slope = 0.9526, Y-intercept = -4.2228. This is reported as correlating "well" with the predicate method. |
| Precision - Within-Run CV% | Not explicitly stated but generally expected to be low (e.g., typically < 10% for diagnostic assays, especially at higher concentrations) | Control Level 1: 3.71%Control Level 2: 3.87%Control Level 3: 3.54%Serum Level 1: 4.69%Serum Level 2: 2.37%Serum Level 3: 4.80% |
| Precision - Total CV% | Not explicitly stated but expected to be low and within acceptable laboratory limits. A total precision of <10% to 15% is common, with lower percentages desired. | Control Level 1: 5.10%Control Level 2: 4.30%Control Level 3: 4.40%Serum Level 1: 5.20%Serum Level 2: 3.58%Serum Level 3: 5.30% |
| Linearity | The assay should demonstrate linearity across its reportable range. | Linear from 13.2 to 615.9 ng/mL. |
| Interference | Less than 10% deviation from the true value when tested with common interferents at specified concentrations. | Less than 10% deviation for all listed interferents at specified concentrations, except for Intralipid above 125 mg/dL. |
The document states, "These results meet the acceptance criteria" under the "Precision" section, implying that the reported precision values are within the pre-defined limits. The "Method Comparison" also states that the results "correlated well," implying acceptance.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Method Comparison: 66 human plasma samples.
- Precision:
- 3 levels of serum-based controls (N=80 for each level across 20 days, 2 runs/day, duplicates means 2022 = 80 measurements per control level).
- 3 serum samples (N=80 for each level, calculated the same way as controls).
- Linearity: Not specified as a number of individual samples, but prepared by mixing a low and high serum-based sample.
- Interference: Not specified.
- Data Provenance: The document does not explicitly state the country of origin for the human plasma and serum samples. It implies prospective testing, as samples were "tested with the Diazyme Myoglobin Assay," suggesting they were collected for the purpose of this study, but this is not explicitly confirmed for all studies. The samples are described as "human plasma samples" and "serum samples", indicating clinical origin rather than synthetic.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Not applicable. This device is an in vitro diagnostic (IVD) assay for quantitative measurement of myoglobin. Ground truth for such assays is typically established through reference methods or highly characterized predicate devices, not expert consensus, pathology reviews, or outcome data in the same way an imaging or classification AI/CAD device would use. In this case, the ground truth for method comparison was the result obtained from the predicate device (Roche Tina-Quant Myoglobin Gen. 2 Test System).
4. Adjudication Method for the Test Set
Not applicable. As noted above, this is an IVD assay, not a device requiring human expert adjudication for ground truth establishment. The performance is assessed against quantitative measurements from a predicate device or by statistical methods for precision and linearity.
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 an in vitro diagnostic assay. MRMC studies are typically performed for imaging devices or CAD systems where human readers interpret results, and the impact of AI assistance on their performance is evaluated. This device provides a quantitative measurement, not an interpretation for a human reader to improve upon.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies reported (method comparison, precision, linearity, interference) represent standalone performance of the Diazyme Myoglobin Assay. The device directly produces a quantitative result of myoglobin concentration in human serum and plasma, with no explicit human-in-the-loop component for result generation. Its performance is evaluated intrinsically through laboratory experiments.
7. The Type of Ground Truth Used
- For Method Comparison: The performance of the predicate device (Roche Tina-Quant Myoglobin Gen. 2 Test System) served as the comparator or "ground truth" to which the Diazyme Myoglobin Assay was compared.
- For Precision, Linearity, and Interference: The "ground truth" is established by the known concentrations of myoglobin in the control materials and the carefully prepared linearity and interference samples. These are quantitative studies where the expected value is either known (for controls/calibrators) or mathematically derived (for linearity/interference).
8. The Sample Size for the Training Set
Not applicable. This device is a chemical assay, not an AI/Machine Learning algorithm that requires a "training set" in the conventional sense. Its performance characteristics are inherent to the chemical reactions and detection system, and are established through analytical verification studies (like those described) rather than machine learning training.
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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510(k) Summary
JUN 0 7 2013
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.
| Submitter's name: | Diazyme Laboratories |
|---|---|
| Submitter's address: | 12889 Gregg CourtPoway, CA 92064USA |
| Name of Contact Person: | Dr. Abhijit DattaDiazyme Laboratories12889 Gregg CourtPoway, CA 92064Phone: 858-455-4762Fax: 858-455-3701 |
| Date the Summary was Prepared: | June 4, 2013 |
| Name of the Device | Diazyme Myoglobin AssayDiazyme Myoglobin Calibrator SetDiazyme Myoglobin Control Set |
| Trade Name: | Diazyme Myoglobin AssayDiazyme Myoglobin Calibrator SetDiazyme Myoglobin Control Set |
| Common/Usual Name | Diazyme Myoglobin Assay |
| Device Classification Name | Myoglobin Test System |
| Product code: | DDR (Myoglobin, Antigen, Antiserum, Control)JIT - Calibrator, SecondaryJJX - Single (specified) Analyte Controls(Assayed and Unassayed) |
| Panel: | Immunology (82) |
| Submission Type | 510k |
| Regulation Number | 21CFR 866.5680 |
| Device Class | Class II |
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Predicate Device:
Roche Tina-Quant Myoglobin Gen. 2 Test System and C.f.a.s. (Calibrators for automated systems) Myoglobin (K061683) Myoglobin Control Set (K973358)
Manufacturing Address
Diazyme Laboratories 12889 Gregg Court Poway, CA 92064 USA
Establishment Registration 2032900
DESCRIPTION OF THE DEVICE
Clinical Significance
Myoglobin is a ~17kDa oxygen-binding protein whose concentration is elevated in response to a muscle injury. Characterized by x-ray crystallography in the 1950s, myoglobin has developed into an important marker for the diagnosis of a recent cardiac event. After a cardiac event or muscle injury occurs, its concentration rises and can be detected in vitro approximately 2 hours after the onset of symptoms and its measurement aids in the diagnosis of ST segment elevated myocardial infarction, which can ultimately lead to cardiac arrest. High concentrations of myoglobin also indicate extensive muscle damage (rhabodmyolysis) and can cause renal failure as high levels of the marker are toxic to the kidneys. The rapid increase in the concentration of myoglobin after muscular trauma makes it an important diagnostic indicator of cardiac stress and muscle damage, and provides early detection of necrosis in cardiac and skeletal muscle.
Assay Principle
The Diazyme Myoglobin Assay is based on a latex enhanced immunoturbidimetric assay. When an antigen-antibody reaction occurs between myoglobin in a sample and anti-myoglobin antibodies which have been sensitized to latex particles, agglutination occurs. This agglutination is detected as an absorbance change (570 nm), with the magnitude of the change being proportional to the quantity of myoglobin in the sample. The actual concentration is then determined by the interpolation from a calibration curve prepared from calibrators of known concentration.
Indications for Use:
The Diazyme Myoglobin Assay is for the quantitative determination of myoglobin in human serum and plasma. Measurement of myoglobin is used as an aid in the diagnosis of acute myocardial infarction. For in vitro diagnostic use only.
The Diazyme Myoglobin Calibrator Set is intended for use in the calibration of the Diazyme Myoglobin Assay. For in vitro diagnostic use only.
The Diazyme Myoglobin Control Set is intended for use as quality controls for the Diazyme Myoglobin Assay. For in vitro diagnostic use only.
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| Table 1 Summarv of Assay Kit Components | ||||
|---|---|---|---|---|
| -- | -- | -- | -- | ----------------------------------------- |
| Roche Tina-Quant Myoglobin Gen. 2,C.f.a.s. Myoglobin (K061683), andMyoglobin Control Set (K973358) | Diazyme Myoglobin Assay |
|---|---|
| Reagent 1buffer solution, ready to use | Reagent 1100 mM Tris buffer solution with 0.09% sodiumazide, ready to use. |
| Reagent 2Suspension of anti-human myoglobincoated latex particles, ready to use | Reagent 2Suspension of latex particles (< 0.5%) coated withgoat anti-human myoglobin with 0.09% sodiumazide, ready to use. |
| CalibratorsReady to use liquid calibratorscontaining myoglobin | CalibratorsLiquid stable calibrators prepared from humanserum, purified human myoglobin, and 0.09%sodium azide. |
| Calibrator set | Calibrator set |
| 3 x 1.0 mL One-Level Calibrator | 1 x 1.0 mL Calibrator 11 x 1.0 mL Calibrator 21 x 1.0 mL Calibrator 31 x 1.0 mL Calibrator 41 x 1.0 mL Calibrator 5 |
| Control Set serum based | Control Set serum based |
| 1 x 3.0mL Control 1 | 1 x 1.0mL Control 1 |
| 1 x 3.0mL Control 2 | 1 x 1.0mL Control 2 |
PERFORMANCE TESTING SUMMARIES
Method Comparison
Human plasma samples were tested with the Diazyme Myoglobin Assay and the obtained results were compared to the predicate method. A total of 66 samples (ranging from 16.9 to 615.9 ng/mL of myoglobin) were tested in both assays. The above described accuracy study showed that the Diazyme Myoglobin Assay results correlated well with predicate method with a correlation coefficient of R2 = 0.9855 with a slope of 0.9526 and -4.2228 y-intercept.
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| Plasma Samples | |
|---|---|
| n | 66 |
| Slope | 0.9526 |
| Intercept | -4.2228 |
| Correlation R2 | 0.9855 |
Precision .
The precision of the Diazyme Myoglobin Assay was evaluated according to Clinical and Laboratory Standards Institute EP5-A guideline. In the study, three levels of serum based controls containing approximately 66, 170, and 335 ng/mL of myoglobin, respectively, and three serum sample containing approximately 35, 150, and 400 ng/mL, of myoglobin, respectively, were tested with 2 runs per day in duplicates over 20 working days. Results were calculated using the EP Evaluator software precision statistic template and summarized in the following table:
Within-Run Precision
| ControlLevel 1 | ControlLevel 2 | ControlLevel 3 | SerumLevel 1 | SerumLevel 2 | SerumLevel 3 | |
|---|---|---|---|---|---|---|
| N | 80 | 80 | 80 | 80 | 80 | 80 |
| Mean | 65.97 | 172.8 | 337.0 | 37.78 | 148.6 | 414.3 |
| SD | 2.45 | 6.69 | 11.9 | 1.77 | 3.53 | 19.7 |
| CV% | 3.71% | 3.87% | 3.54% | 4.69% | 2.37% | 4.80% |
Total Precision
| ControlLevel 1 | ControlLevel 2 | ControlLevel 3 | SerumLevel 1 | SerumLevel 2 | SerumLevel 3 | |
|---|---|---|---|---|---|---|
| N | 80 | 80 | 80 | 80 | 80 | 80 |
| Mean | 65.97 | 172.8 | 337.0 | 37.78 | 148.6 | 414.3 |
| SD | 3.37 | 7.37 | 14.9 | 1.97 | 5.32 | 21.8 |
| CV% | 5.10% | 4.30% | 4.40% | 5.20% | 3.58% | 5.30% |
Conclusion: For the three levels of myoglobin control and three levels of serum specimens, 20day reproducibility data showed that the within-run precision was from 2.37% to 4.80% and total precision was from 3.58% to 5.3%. These results meet the acceptance criteria.
Linearity
A linearity set was prepared by mixing a low serum based sample of myoglobin containing 11 ng/mL and a high serum based sample of myoglobin containing 625 ng/mL, according to CLSI EP6-A. The assay was linear from 13.2 to 615.9 ng/mL.
Interference
The following substances normally present in the blood produced less than 10% deviation when tested at levels equal to the concentrations listed below:
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| Interferent | Concentration |
|---|---|
| Triglyceride | 1000 mg/dL |
| Intralipid | 125 mg/dL |
| Ascorbic Acid | 176 mg/dL |
| Bilirubin | 40 mg/dL |
| Bilirubin Conjugated | 40 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Rheumatoid Factor | 100 IU/mL |
| Heparin | 1.5 IU/mL |
| N-acetylcysteine | 11.04 mM |
| Acetylsalicylic Acid | 2.78 mM |
| Ampicillin | 152 µM |
| Carbamazepine | 0.13 mM |
| Na2-Cefoxitin | 1549 µM |
| Ibuprofen | 2425 µM |
| Ciclosporin | 0.125 µM |
| Levodopa | 30.4 mM |
| Methyldopa | 71 µM |
| Metronidazole | 701 µM |
| Rifampicin | 78.1 µM |
| Theophylline | 222 μM |
| Phenylbutazone | 650 µM |
| Valproic Acid, Sodium Salt | 3.5 mM |
The assay has no intralipid interference below 125 mg/dL. Specimens from patients undergoing Intralipid therapy may have interference with the Myoglobin Assay.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, with three wavy lines representing the staff and a single line representing the snake.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 7, 2013
Diazyme Laboratories C/O Abhijit Datta, Ph.D. 12889 Gregg Court POWAY CA 92064
Re: K123785
Trade/Device Name: Diazyme Myoglobin Assay Diazyme Myoglobin Calibrator Set Diazyme Myoglobin Control Set
Regulation Number: 21 CFR 866.5680 Regulation Name: Myoglobin immunological test system Regulatory Class: II Product Code: DDR, JIT, JJX Dated: April 26, 2013 Received: April 30, 2013
Dear Dr. Datta:
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 forth in the quality systems (OS) 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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Page 2-Dr. Datta
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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 Small Manufacturers, International and Consumer Assistance 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.
Sincerely yours,
Carol C. Benson -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: K123785
Device Name: Diazyme Myoglobin Assay, Diazyme Myoglobin Calibrator Set, Diazyme Myoglobin Control Set
Indications for Use:
The Diazyme Myoglobin Assay is for the quantitative determination of myoglobin in human serum and plasma. Measurement of myoglobin is used as an aid in the diagnosis of acute myocardial infarction. For in vitro diagnostic use only.
The Diazyme Myoglobin Calibrator Set is intended for use in the calibration of the Diazyme Myoglobin Assay. For in vitro diagnostic use only.
The Diazyme Myoglobin Control Set is intended for use as quality controls for the Diazyme Myoglobin Assay. For in vitro diagnostic use only.
Prescription Use X (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Ruth A. Cheslêr -S
Division Sign-Off Office of In Vitro Diagnostics and Radiological Health
510(k) K123785
Page 1 of 1
§ 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).