(123 days)
The EasyRA HDL Cholesterol reagent is intended for the quantitative determination of High Density Lipoprotein Cholesterol in human serum on the Medica EasyRA Chemistry Analyzer. The Medica EasyRA HDL-Cholesterol reagent can assist in the diagnosis and treatment of patients at risk of developing coronary heart disease.
Medica's HDL cholesterol reagent consists of two parts R1 and R2. The first step involves the removal of other non-HDL lipoproteins via selective reaction with reagent R1. In the second step, the selective detergent in R2 solubilizes the HDL cholesterol specifically, which then reacts with a chromagen to develop a color that can be read optically at 600nm. The intensity of the color is proportional to the concentration of HDL cholesterol in the sample.
Here's an analysis of the acceptance criteria and study details for the Medica Corporation EasyRA HDL Cholesterol Reagent, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
For this specific device (a reagent for an in-vitro diagnostic test), acceptance criteria are typically related to analytical performance characteristics. The document doesn't explicitly state "acceptance criteria" as a pass/fail threshold, but rather reports the performance demonstrated, implying that these levels met regulatory expectations for substantial equivalence.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Linearity | Linear throughout clinical range | 2 to 150 mg/dL |
| Within-Run Precision | CV% ≤ 3% (typical for QC materials) | Bio-Rad L1: 1.9% - 2.2% CV%Randox L2: 1.0% - 1.5% CV% |
| Total Precision | CV% ≤ 3% (typical for QC materials) | Bio-Rad L1: 2.47% - 2.51% CV%Randox L2: 1.91% - 2.12% CV% |
| Method Comparison | Excellent correlation with predicate device | "correlated excellently" with predicate device (Genzyme HDL Cholesterol Reagent for Cobas-Mira) |
| Sample Carryover | No evidence of carryover | No evidence of sample carryover |
| Analytical Sensitivity (Limit of Detection) | Low limit needed for clinical relevance | 0.86 mg/dL |
| Functional Sensitivity | Low limit needed for clinical relevance | 1.3 mg/dL |
| Interference | No significant interference at specified concentrations | Hemoglobin: No interference up to 500mg/dlBilirubin: No interference up to 32.5mg/dlLipemia: No interference up to 1000mg/dl |
2. Sample Size Used for the Test Set and Data Provenance
- Linearity: Not explicitly stated beyond "commercial linearity standards." These are typically synthetic or pooled human samples.
- Within-Run Precision: Five replicates of two levels of commercial serum-based QC material tested each day for five days. This is a total of 5 replicates * 2 levels * 5 days = 50 measurements per analyzer, across three analyzers. So, 150 data points in total for each QC level across the three analyzers. The samples were "commercial serum-based Quality control material". The provenance is not specified (e.g., country of origin, retrospective/prospective), but given they are commercial QC materials, they would likely be manufactured under controlled conditions.
- Total Precision: Two levels of commercial serum-based QC material tested in duplicate twice daily for 20 days. This is a total of 2 replicates * 2 times/day * 20 days = 80 measurements per analyzer, across three analyzers. So, 240 data points in total for each QC level across the three analyzers. The samples were "commercial serum-based Quality control material." Provenance not specified.
- Method Comparison: "At least 40 samples" were tested. The provenance is not specified, but these would typically be human serum samples, likely collected prospectively or retrospectively from a local population at the time of the study.
- Sample Carryover: "Eleven samples" (L, M, H range) were analyzed. Provenance not specified.
- Sensitivity: "20 replicates of reagent grade water." Provenance is irrelevant as it's a non-biological sample.
- Interference Testing: Not specified, but involved specific concentrations of hemoglobin, bilirubin, and intralipid, likely spiked into a normal serum matrix.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of device (a diagnostic reagent for a chemistry analyzer) does not typically rely on human expert interpretation for "ground truth" in the same way an imaging or pathology device would. The "ground truth" for the test set is established by:
- Reference Methods/Materials: For linearity, it's NIST-traceable commercial linearity standards.
- Predicate Device: For method comparison, the "ground truth" is established by the measurements from the legally marketed predicate device (Genzyme HDL Cholesterol Reagent on a Cobas-Mira analyzer).
- Known Concentrations: For precision, it's known concentrations in commercial quality control materials.
- Spiked Samples: For interference, it's known concentrations of interferents added to serum.
Therefore, the concept of "number of experts" and "qualifications of those experts" for establishing ground truth is not applicable in this context. The accuracy of the "ground truth" relies on the validated performance of the reference methods, predicate device, and QC materials used.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation or subjective assessments. Since this is an analytical performance study of an in-vitro diagnostic reagent, such adjudication methods are not applicable. The measurements are quantitative and objectively determined by the analyzer.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are relevant for devices where human readers or interpreters interact with the device's output (e.g., interpreting medical images with or without AI assistance). This device is a reagent for an automated chemistry analyzer, producing quantitative numerical results, not requiring human interpretation as part of the primary diagnostic step.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, the studies described are essentially standalone performance studies of the reagent on the EasyRA analyzer. The performance metrics (linearity, precision, method comparison, sensitivity, interference) evaluate the reagent and analyzer system's ability to accurately and precisely measure HDL cholesterol without human intervention affecting the measurement itself. The "algorithm" here is the chemical reaction and photometric measurement process implemented by the reagent and analyzer.
7. Type of Ground Truth Used
- NIST-traceable commercial linearity standards: For linearity.
- Commercial serum-based Quality control material with known target values: For precision.
- Measurements from a legally marketed predicate device (Genzyme HDL Cholesterol Reagent on Cobas-Mira): For method comparison.
- Reagent grade water: For sensitivity.
- Serum samples spiked with known concentrations of interferents: For interference testing.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of device development. For an IVD reagent, method development involves extensive experimentation and optimization, but it's not typically quantified as a "training set" in the same way a machine learning algorithm would have one. The performance studies described are validation studies, not training studies.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" is described for this type of IVD reagent, this question is not fully applicable. The development process would involve establishing "ground truth" through various analytical chemistry principles, using reference materials, and comparing results to established methods to optimize the reagent's formulation and reaction conditions.
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K073497
December 6, 2007
Medica Corporation 510(k) Submission EasyRA HDL Cholesterol Reagent
Page 22
510(k) Summary
| Date of summary: | December 6, 2007 | APR 14 2008 |
|---|---|---|
| Product Name: | HDL Cholesterol Reagent | |
| Manufacturer: | Medica Corporation5 Oak Park DriveBedford, MA 01730 | |
| Correspondent: | Photios MakrisDirector QA/RAMedica Corporation5 Oak Park DriveBedford, MA 01730 |
Substantial Equivalent Device:
| Manufacturer: | Genzyme Corporation | |
|---|---|---|
| Product: | Cobas Ready HDL Cholesterol Reagent |
| ProductAttribute | Medica HDL CholesterolReagent | Genzyme HDL CholesterolReagent for Cobas-Mira | SubstantialEquivalent |
|---|---|---|---|
| Intended Use | Clinical chemistry reagentused to provide aquantitative measurement ofHigh Density Lipoprotein(HDL) in human serumusing the EasyRA chemistryanalyzer. | Clinical chemistry reagentused to provide a quantitativemeasurement of HighDensity Lipoprotein (HDL)in human serum using theRoche Cobas-Mira chemistryanalyzer. | √ |
| Sample | Serum | Serum | √ |
| TestMethodology | EasyRA ready-to-useenzymatic assay reagent | Cobas-Mira ready-to-useenzymatic assay reagent | √ |
The EasyRA HDL cholesterol reagent is intended for the quantitative Intended Use: determination of High Density Lipoprotein Cholesterol in human serum, using the Medica "EasyRA Chemistry analyzer" in clinical laboratories to screen for low HDL levels as a risk factor in coronary artery disease.
For in-vitro diagnostic use only. For professional use only
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Medica's HDL cholesterol reagent consists of two parts R1 and R2. Methodology: The first step involves the removal of other non-HDL lipoproteins via selective reaction with reagent R1. In the second step, the selective detergent in R2 solubilizes the HDL cholesterol specifically, which then reacts with a chromagen to develop a color that can be read optically at 600nm. The intensity of the color is proportional to the concentration of HDL cholesterol in the sample.
Performance Data:
Linearity:
Linearity studies, based on CLSI EP-6A, were performed using NIST-traceable commercial linearity standards on the EasyRA Chemistry analyzers. The HDL cholesterol reagent is linear from 2 to 150mg/dL.
Within-Run Precision:
Within-run precision was determined following CLSI EPA-A2. Five replicates of two levels of a commercial serum-based Quality control material were tested each day for five days on three analyzers.
| Bio-Rad L1 | Randox L2 | |||
|---|---|---|---|---|
| EasyRA #2 | EasyRA #3 | EasyRA #2 | EasyRA #3 | |
| Grand Mean | 32.5 | 32.1 | 64.3 | 62.8 |
| Std. Dev. | 0.63 | 0.69 | 0.94 | 0.62 |
| CV% | 1.9% | 2.2% | 1.5% | 1.0% |
EasyRA HDL cholesterol reagent Within-run precision
Total Precision:
Total precision was determined following CLSI EPA-A2. Two levels of a commercial serum-based Quality control material werc tested in duplicate twice daily for 20 days on three EasyRA nalyzers.
| Bio-Rad L1 | Randox L2 | |||
|---|---|---|---|---|
| EasyRA #2 | EasyRA #3 | EasyRA #2 | EasyRA #3 | |
| Grand Mean | 33.1 | 33.2 | 64.6 | 64.2 |
| Std. Dev. | 0.82 | 0.84 | 1.37 | |
| CV% | 2.47% | 2.51% | 2.12% | 1.91% |
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Method Comparison:
Method comparison was based on EP7-A. At least 40 samples were tested in two EasyRA analyzers using Medica's reagent and in duplicate on a Cobas Mira analyzer using the Genzyme reagent. Medica's HDL cholesterol reagent correlated excellently with the predicate device.
Sample carryover:
Sample carryover, within run drift, was tested based on CLSI EP10-A2. Eleven samples were analyzed that are L (low), M (mid-range) and H (high) range in a predefined sequence twice in a single day. There was no evidence of sample carryover.
Sensitivity:
The limit of detection, or analytical sensitivity, was determined by testing 20 replicates of reagent grade water, then calculating the mean plus two standard deviation units (mean + 2SD). The functional sensitivity was determined as the reagent grade water mean, as determined above, plus seven standard deviation units (mean + 7SD).
The analytical sensitivity of the EasyRA HDL cholesterol reagent is 0.86 mg/dl and the lower limit of detection is 1.3 mg/dl.
Interference testing:
Testing for interference substances was based on CLSI EP-7A. The following substances were tested: Hemoglobin to 500 mg/dl; Billirubin to 20 mg/dl; and Lipemia (using intralipid).
| Hemoglobin | No interferences up to 500mg/dl |
|---|---|
| Billirubin | No interferences up to 32.5mg/dl |
| Lipemia | No interferences up to 1000mg/dl |
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Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized eagle with three tail feathers, representing the department's commitment to health, human services, and well-being. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle.
Food and Druq Administration 2098 Gaither Road Rockville MD 20850
Medica Corp. c/o Photios Makris 5 Oak Park Drive Bedford, MA 01730
APR 1 4 2008
K073497 Re:
Trade/Device Name: Hdl Cholesterol Reagent, Model 10211 Regulation Number: 21 CFR §862.1475 Regulation Name: Lipoprotein test system Regulatory Class: Class I, meets the limitations to exemption in 21 CFR 862.9(c)(4) Product Code: LBS, JIT Dated: February 28, 2008 Received: March 03, 2008
Dear Mr. Makris:
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 (240) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Jean M. Cooper, M.S., D.V.M.
Yean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Page 25
Indications for Use
K073497 510(k) Number:
Device Name: EasyRA HDL Cholesterol Reagent
Indications for Use:
The EasyRA HDL Cholesterol reagent is intended for the quantitative determination of High Density Lipoprotein Cholesterol in human serum on the Medica EasyRA Chemistry Analyzer. The Medica EasyRA HDL-Cholesterol reagent can assist in the diagnosis and treatment of patients at risk of developing coronary heart disease.
EasyRA HDL Cholesterol Calibrator Device Name:
Indications for Use:
The EasyRA HDL Cholesterol calibrator is intended for the one point calibration of the HDL reagent prior to patient serum sample analysis on the EasyRA clinical chemistry analyzer.
For in-vitro diagnostic use only. For Professional use only.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitye Diagnostic Devices (OIVD)
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
§ 862.1475 Lipoprotein test system.
(a)
Identification. A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.