(137 days)
The Diazyme LDL-Cholesterol Assay is intended for the in vitro quantitative determination of Low Density Lipoprotein Cholesterol in human serum or plasma. The reagents can assist in the diagnosis and treatment of patients at risk of developing coronary heart disease. Elevated LDL cholesterol is the primary target of cholesterol-lowering therapy.
The assay is based on a modified polyvinyl sulfonic acid (PVS) and polyethylene-glycol methyl ether (PEGME) coupled classic precipitation method with the improvements in using optimized quantities of PVS/PEGME and selected detergents. LDL, VLDL. and chylomicron (CM) react with PVS and PEGME and the reaction results in inaccessibility of LDL, VLDL and CM by cholesterol oxidase (CHOD) and cholesterol esterase (CHER), whereas HDL reacts with the enzymes. Addition of R2 containing a specific detergent releases LDL from the PVS/PEGME complex. The released LDL reacts with the enzymes to produce H2O2 which is quantified by the Trinder reaction.
Here's an analysis of the acceptance criteria and study details for the Diazyme LDL-Cholesterol Reagent, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state "acceptance criteria" as distinct, quantifiable thresholds that the device must meet on its own for approval. Instead, the performance of the Diazyme LDL-Cholesterol Reagent is presented and compared primarily to a legally marketed predicate device (Genzyme N-Geneous LDL Cholesterol Reagent, K971573) to demonstrate substantial equivalence. The implication is that performance comparable to the predicate (and within generally accepted clinical laboratory standards for such assays) constitutes the acceptance.
Therefore, the table below reflects the reported performance of the Diazyme device and, for comparison, the predicate device as presented in the submission. The "acceptance criteria" are inferred as comparable performance to the predicate and generally good laboratory practice for quantitative assays.
| Performance Metric | Diazyme LDL-Cholesterol Reagent Reported Performance | Inferred Acceptance Criteria (based on predicate & good lab practice) |
|---|---|---|
| Reportable Range | Serum: 2.04 - 250 mg/dL | Comparable to predicate (6.6-992 mg/dL) and clinically relevant. Diazyme's range is narrower on the high end but acceptable. |
| Linearity | 1.64 - 830 mg/dL (for serum samples) | Sufficiently wide to cover clinically relevant range. |
| Precision (Within Run) | 0.7% - 1.0% ($C_v$%) at different LDL levels ($95, 146, 210 mg/dL$) | Comparable to predicate (0.62% - 0.73%) and within expected analytic variability for clinical assays. |
| Precision (Total) | 1.4% - 1.6% ($C_v$%) at different LDL levels ($95, 146, 210 mg/dL$) | Comparable to predicate (1.73% - 2.27%) and within expected analytic variability for clinical assays. |
| Accuracy (Correlation Coefficient vs. Predicate) | 0.996 (for serum samples) | High correlation (e.g., > 0.95) with a legally marketed device. |
| Accuracy (Slope/Intercept vs. Predicate) | y = 1.0883x + 0.6078 mg/dL | Slope close to 1 and intercept close to 0 when compared to a legally marketed device. (Predicate: y = 0.95x + 3.02mg/dL) |
| Interference | Less than 10% interference with: | Minimal interference from common endogenous substances at specified concentrations. |
| - Triglycerides (1000 mg/dL) | ||
| - Ascorbic acid (10 mmol/L) | ||
| - Bilirubin (40 mg/dL) | ||
| - Bilirubin Conjugated (40 mg/dL) | ||
| - Hemoglobin (1000 mg/dL) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document repeatedly mentions "samples tested with Diazyme LDL-Cholesterol Reagent showed good correlation with Genzyme N-geneous LDL Cholesterol Reagent (K971573) with correlation coefficients of 0.996 for serum samples" and refers to "clinical patient samples." However, the exact number of samples used for the method comparison (test set) is not explicitly stated in the provided text.
- Data Provenance: The text does not specify the country of origin of the data. It is implied that the data is retrospective, as it involves "samples tested" and a comparison was made using these samples. The term "clinical patient samples" also suggests that these were real-world samples collected from patients.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the document. For an in vitro diagnostic reagent like this, the "ground truth" for the test set is established by testing the same samples using a well-established, often reference, method or a legally marketed predicate device. The expertise lies in the laboratory performing the tests and ensuring proper execution, not typically in a panel of experts reviewing the results in the same way as, for example, image-based diagnostics.
In this case, the predicate device (Genzyme N-geneous LDL Cholesterol Reagent) serves as the comparator or "reference" for demonstrating substantial equivalence. The ground truth for the predicate device itself is stated to be traceable to the CDC HDL reference method, which is a highly standardized and rigorous method.
4. Adjudication Method for the Test Set
This is not applicable in the context of this type of quantitative diagnostic assay. Adjudication methods (like 2+1 or 3+1) are typically used in studies involving subjective interpretation, such as image analysis where multiple readers might disagree, and a consensus needs to be formed for the ground truth. Here, the "truth" is a quantitative value obtained from a chemical reaction. The comparison is statistical, between two quantitative 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
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for AI-powered diagnostic devices, especially in imaging, where human readers interpret results with and without AI assistance. The Diazyme LDL-Cholesterol Reagent is a laboratory reagent for quantitative chemical analysis, not an AI-assisted diagnostic tool that aids human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
The entire performance evaluation described for the Diazyme LDL-Cholesterol Reagent is a standalone (algorithm/reagent only) performance. The device is a reagent system that produces a quantitative result. There is no "human-in-the-loop" in the interpretation of the final quantitative value (though humans operate the instruments and handle the samples). The accuracy and precision data presented are reflective of the reagent's performance on its own.
7. The Type of Ground Truth Used
The ground truth used for comparison (and thus, implicitly, for evaluating the Diazyme device) is derived from the results obtained from a legally marketed predicate device (Genzyme N-geneous LDL Cholesterol Reagent, K971573). The submission states: "Genzyme N-geneous LDL Cholesterol Reagent (K971573) was selected for comparing serum samples with to the results generated by Diazyme LDL-Cholesterol Reagent." The predicate device itself traces its calibrator to the NIST SRM 1915b and its method to the CDC HDL reference method, indicating a robust underlying ground truth reference.
8. The Sample Size for the Training Set
This information is not applicable and therefore not provided in the document. The Diazyme LDL-Cholesterol Reagent is a chemical reagent assay, not an AI/machine learning model that requires a "training set." Its operating parameters (e.g., reagent concentrations, reaction times) would be optimized during its development process, but this is a different concept from training an algorithm.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable as there is no "training set" in the context of this chemical reagent device.
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K072523
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
| Submitter's name: | Diazyme Laboratories |
|---|---|
| Submitter's address: | 12889 Gregg CourtPoway, CA 92064USA |
| Name of Contact Person: | Charles YuDiazyme Laboratories12889 Gregg CourtPoway, CA 92064Phone: 858-455-4761Fax: 858-455-4750 |
| Date the Summary was Prepared: | August 22, 2007 |
| Name of the Device | Diazyme LDL-Cholesterol Reagent |
| Trade Name: | Diazyme LDL-Cholesterol Reagent |
| Common/Usual Name | Lipoprotein Test System |
| Device Classification Name | Low Density Lipoprotein Cholesterol Reagent |
| Product code: | LBR, JIS, JIX |
| Submission Type | 510k |
| Regulation Number | 862.1475 |
| Device Class | II |
| Predicate Device: | For the Lipoprotein test system, we are claiming equivalence [807.92(a) (3) to N-GENEOUS LDL CHOLESTEROL REAGENT (K971573) manufactured by GenzymeDiagnostics |
:
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Substantial Equivalence Information
1. Predicate device name(s):
Genzyme N-Geneous LDL Cholesterol Reagent
2. Predicate 510(k) number(s):
3. Comparison with predicate:
Indications for Use
| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL CholesterolReagent | Equivalency |
|---|---|---|
| The Diazyme LDL-Cholesterol Assay isintended for the in vitro quantitativedetermination of Low Density LipoproteinCholesterol in human serum or plasma. Thereagents can assist in the diagnosis andtreatment of patients at risk of developingcoronary heart disease. Elevated LDLcholesterol is the primary target ofcholesterol-lowering therapy. | For the direct, quantitative measurement oflow density lipoprotein cholesterol (LDL-C) concentration in human serum orplasma. | Same |
Principle
| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL CholesterolReagent | Equivalency |
|---|---|---|
| The assay is based on a modified polyvinylsulfonic acid (PVS) and polyethylene-glycol-methyl ether (PEGME) coupled classic pre-cipitation method with the improvements inusing optimized quantities of PVS/PEGMEand selected detergents. LDL, VLDL, andchylomicron (CM) react with PVS andPEGME and the reaction results in inaccessi-bility of LDL, VLDL and CM by cholesteroloxidase (CHOD) and cholesterol esterase(CHER). The enzymes selectively react withHDL to produce H2O2 which is detectedthrough a Trinder reaction. | This method is in a two reagent format anddepends on the properties of a unique de-tergent. This detergent ( Reagent 1) solubi-lizes only the non LDL lipoprotein parti-cles. The cholesterol released is consumedby cholesterol esterase and cholesterol oxi-dase in a non color forming reaction. Asecond detergent (Reagent 2) solubilizesthe remaining LDL particles and a chro-mogenic coupler allows for color forma-tion. The enzyme reaction with LDL-C inthe presence of the coupler produces colorthat is proportional to the amount of LDLcholesterol present in the sample. | Similar |
Test Objective
| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL CholesterolReagent | Equivalency |
|---|---|---|
| For the in vitro quantitative determinationof low density lipoprotein cholesterol inhuman serum or plasma. | For the direct, quantitative measurement oflow density lipoprotein cholesterol (LDL-C) concentration in human serum orplasma. | Same |
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Type of Test
| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL CholesterolReagent | Equivalency |
|---|---|---|
| Quantitative | Quantitative | Same |
Specimen Type
| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL CholesterolReagent | Equivalency |
|---|---|---|
| Human serum or plasma | Human serum or plasma | Same |
Product Type
| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL CholesterolReagent | Equivalency |
|---|---|---|
| Calibrator, Reagent, Instrument | Calibrator, Reagent, Instrument | Same |
Performance
| Diazyme LDL-Cholesterol Reagent | Genzyme N-Geneous LDL Cholesterol Reagent |
|---|---|
| Reportable Range:Serum: 2.04 - 250 mg/dL | Reportable Range:Serum: 6.6-992mg/dL |
| Precision/Serum:Within Run: 0.7% -1.0%Total: 1.4%-1.6% | Precision/Serum:Within Run: 0.62% -0.73%Total: 1.73%-2.27% |
| Accuracy/Serum:Correlation Coefficient: 0.9804Slope/Intercept:y = 1.0883x + 0.6078 mg/dL | Accuracy/Serum:Correlation Coefficient: 0.96Slope/Intercept:y = 0.95x + 3.02mg/dL |
Calibrator Comparison
| Diazyme LDL Cholesterol Calibrator | Genzyme N-Geneous LDL CholesterolCalibrator | Equivalency |
|---|---|---|
| Lyophilized form | Lyophilized form | Same |
| LDL Cholesterol calibrator is traceable to NISTSRM 1915b. | LDL N-Geneous calibrator is traceable tothe CDC HDL reference method**. | Same |
** National Reference System for Cholesterol. CRMLN LDL Cholesterol Protocol, May 2004.
:
·
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Rationale for Considering the Device Substantially Equivalent to Devices Approved for Interstate Commerce
Genzyme N-geneous LDL Cholesterol Reagent (K971573) was selected for comparing serum samples with to the results generated by Diazyme LDL-Cholesterol Reagent. Detailed performance characteristics and comparison analysis are given in this filing and demonstrate substantial equivalence to predicate device that is currently being legally marketed.
The Diazyme LDL-Cholesterol Reagent is similar to the approved predicate test. The minor differences in the performances of the tests should not affect the safety and effectiveness of the Diazyme LDL - Cholesterol Reagent and offers users an in-vitro diagnostic device to measure LDL Cholesterol in human serum or plasma.
In summary, the dissimilar features between the Diazyme LDL-Cholesterol Reagent and devices currently legally marketed do not affect the safety or effectiveness of the device. This is supported by the accuracy data comparing serum sample values obtained using the Diazyme LDL-Cholesterol Reagent with those obtained using the predicate device, Genzyme N-geneous LDL Cholesterol Reagent (K971573).
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Description of the Device
The assay is based on a modified polyvinyl sulfonic acid (PVS) and polyethylene-glycol methyl ether (PEGME) coupled classic precipitation method with the improvements in using optimized quantities of PVS/PEGME and selected detergents. LDL, VLDL. and chylomicron (CM) react with PVS and PEGME and the reaction results in inaccessibility of LDL, VLDL and CM by cholesterol oxidase (CHOD) and cholesterol esterase (CHER), whereas HDL reacts with the enzymes. Addition of R2 containing a specific detergent releases LDL from the PVS/PEGME complex. The released LDL reacts with the enzymes to produce H2O2 which is quantified by the Trinder reaction.
PVS HDL + LDL + VLDL + CM = + PEGME HDL + (LDL + VLDL + CM ) · PVS/PEGME HDL + CHER - -- Fatty Acid + H3O2 Detergent (LDL + VLDL + CM)· PVS/PEGME LDL + (VLDL + CM) · PVS/PEGME LDL + CHOD + CHER ------------------------------------------------------------------------------------------------------------------------------------------------------------Peroxidase 2H2O2 +4-AA+TODB -------------------------------------------------------------------------------------------------------------------------------------------------------------(2-max=560nm)
Intended Use of the Device:
The Diazyme LDL-Cholesterol Reagent is intended for the in vitro quantitative determination of Low Density Lipoprotein Cholesterol in human serum or plasma. The reagents can assist in the diagnosis and treatment of patients at risk of developing coronary heart disease. Elevated LDL cholesterol is the primary target of cholesterol-lowering therapy.
Performance Characteristics
Diazyme LDL-Cholesterol Reagent is a homogeneous two-reagent enzymatic assay. The results are obtained in 10 minutes by measuring absorbance at 600 nm. The linearity of the assay is from 1.64 -830 mg/dL for serum samples. The assay offers excellent precision as shown in the tables below:
| Serum Testing | Level 195mg/dL LDL | Level 2146mg/dL LDL | Level 3210mg/dL LDL |
|---|---|---|---|
| Within-Run Precision | $C_v$ % = 1.0% | $C_v$ % = 0.8% | $C_v$ % = 0.7% |
| Total Precision | $C_v$ % = 1.6% | $C_v$ % = 1.5% | $C_v$ % = 1.4% |
In method comparison studies, samples tested with Diazyme LDL-Cholesterol Reagent showed good correlation with Genzyme N-geneous LDL Cholesterol Reagent (K971573) with correlation coefficients of 0.996 for serum samples.
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We have conducted interference studies by spiking normal pooled human serum samples with substances normally present in serum or plasma and found less than 10% interference at the indicated concentrations.
| Interference Study | |
|---|---|
| Substance | Concentration |
| Triglycerides | 1000 mg/dL |
| Ascorbic acid | 10 mmol/L |
| Bilirubin | 40 mg/dL |
| Bilirubin Conjugated | 40 mg/dL |
| Hemoglobin | 1000 mg/dL |
:
Conclusion: Comparison analysis presented in this 510k submission filing in the comparison section, together with linearity, precision and interference and other detailed studies, demonstrates that the Diazyme LDL-Cholesterol Reagent has excellent accuracy and is safe and effective. There is no significant deviation between the results obtained by Diazyme LDL-Cholesterol Reagent and the legally marketed predicate device (K971573) when testing clinical patient samples and is therefore substantially similar.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its head turned to the left and its wings outstretched. The eagle is composed of three thick, black lines. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.
Public Health Service
JAN 22 2008
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
General Atomics Diazyme Laboratories Division c/o Mr. Charles Yu 12889 Gregg Court Poway, CA 92064
Re: K072523
Trade/Device Name: Diazyme LDL-Cholesterol Reagent Regulation Number: 21 CFR§862.1475 Regulation Name: Lipoprotein Test System Regulatory Class: Class I Product Code: LBR, JJX Dated: November 12, 2007 Received: November 15, 2007
Dear Mr. Yu:
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.
Jean 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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Indications for Use
| 510(k) Number: | K 072523 |
|---|---|
| Device Name: | Diazyme LDL-Cholesterol Reagent |
| Indications for Use: | The Diazyme LDL-Cholesterol Assay is intended for the in vitro quantitativedetermination of Low Density Lipoprotein Cholesterol in human serum orplasma. The reagents can assist in the diagnosis and treatment of patients atrisk of developing coronary heart disease. Elevated LDL cholesterol is theprimary target of cholesterol-lowering therapy. |
| Calibrator: | For calibration of the Diazyme LDL-Cholesterol Reagent Assay inserum or plasma.For In Vitro Diagnostic Use |
| Controls: | To monitor the performance of Diazyme LDL-Cholesterol Reagent.For In Vitro Diagnostic Use |
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)
| Signature | Carol Benson Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD) |
|---|---|
| Division Sign-Off |
510(k) Summary
| Office of In Vitro Diagnostic Device | |
|---|---|
| Evaluation and Safety | 15 |
§ 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.