(51 days)
The LIPID CAL is an in vitro diagnostic product for the calibration of high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) methods on the Dimension Vista™ System.
LIPID CAL is a liquid, multi-analyte, human albumin based product containing human lipoproteins and bovine gamma globulins. The kit consists of six vials, three vials of Calibrator A, and three vials of Calibrator B which are ready for use (no preparation is required). The volume per vial is 1.5 mL.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Dimension Vista™ System Lipid Calibrator:
This document describes a diagnostic calibrator, not a device with a single performance metric like accuracy or sensitivity against a clinical outcome. Therefore, the "acceptance criteria" here refer to the stability of the calibrator material itself and its ability to consistently produce accurate values when used with the Dimension Vista™ System. The primary "study" described is a stability study and a batch value assignment and verification process.
1. Table of Acceptance Criteria and Reported Device Performance
For this calibrator, the performance is described primarily through its stability and the rigorous process for assigning its values.
| Acceptance Criteria Category | Specific Criteria | Reported Performance / Study Outcome |
|---|---|---|
| Shelf-Life Stability (Unopened Vial) | Percent change over time should be less than or equal to 3% when compared to control stored at -20°C. Target shelf life is 12 months at 4°C. | "Recovery versus time is monitored and percent change over time is determined. Percent change should be less than or equal to 3%. Shelf-life stability (expiration) dating assignment at commercialization reflects the real-time data on file at Dade Behring, Inc." (This indicates the criteria were met and used to establish the 12-month shelf life). |
| On-Board Stability (Punctured Vial) | Not explicitly stated as a percentage, but linked to a 7-day claim. | "A vial punctured by the instrument and stored on board has a seven day claim." (Implies performance within acceptable limits for 7 days). |
| Open Vial Stability (Recapped & Refrigerated) | Not explicitly stated as a percentage, but linked to a 30-day claim. | "An open vial not stored on board of instrument, but recapped and stored in a refrigerator has a stability claim of 30 days." (Implies performance within acceptable limits for 30 days). |
| Open Vial Stability Testing (Methodology) | Ensure consistency over time when compared to freshly opened vials. | "For testing, vials are opened /punctured on day zero. A quantity sufficient for multiple calibrations is removed and the vials are recapped and stored at 2 - 8 °C. Opened/punctured vials are tested on days 8, 15, 22, and 32 versus freshly opened vials." (This describes the method of testing, implying the results supported the 7 and 30-day claims). |
| Bottle Value Assignment Verification | Not explicitly stated as a percentage or specific range, but implies values must be consistent across multiple instruments. | "The final bottle values for each level of the commercial lot is assigned and verified using multiple instruments by testing N = 90 replicates." (This demonstrates a rigorous process to ensure assigned values are correct and consistent.) |
| Traceability | Values must be traceable to established reference methods/materials. | HDLC and LDLC are traceable to the "National Cholesterol Education Program (NCEP) reference method." |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: For the Bottle Value Assignment, which can be considered a test of the commercial lot's performance, N=90 replicates were tested.
- Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. Given the context of a 510(k) submission by Dade Behring Inc. in Newark, DE, USA, it's highly probable the studies were conducted in the USA and were prospective studies specifically designed for regulatory submission.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- Number of Experts: This type of calibrator does not typically involve "experts" in the sense of clinical decision-making. Instead, its "ground truth" (assigned values) is established through traceability to reference methods and reference laboratories.
- For HDLC: "Human HDL ... with Abel-Kendall values are used to produce a standard curve for the assignment of the Master Pool." (Abel-Kendall is a CDC reference method for cholesterol).
- For LDLC: "LDL human serum pools with values from reference laboratories (CRMNL) are used to produce a standard curve for assignment of the Anchor Pool." (CRMNL likely refers to the CDC Reference Methods for Novel Lipoproteins).
- Qualifications of Experts: The "experts" are the established reference methods and laboratories (e.g., NCEP, Abel-Kendall, CRMNL), which are recognized for their accuracy and precision in lipid measurements. No specific individual expert qualifications are provided, as the expertise resides in the methodology and certified laboratories.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used for subjective clinical interpretations (e.g., imaging studies where experts disagree). For a quantitative calibrator, adjudication as commonly understood is not applicable. The "ground truth" is established by the agreement to reference measurement procedures and subsequent statistical verification (N=90 replicates for bottle value assignment). Discrepancies would be handled through re-measurement against the reference or investigation of the measurement system.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. MRMC studies are relevant for devices where a human observer's performance (e.g., reading an X-ray) is being evaluated, often with or without AI assistance. This document describes a calibrator material, which is used to ensure the accuracy of an automated measurement system, not to aid human interpretation or diagnosis directly in an MRMC setting.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
This question is framed for an AI algorithm. For a calibrator, the "standalone" performance would refer to its inherent stability and the accuracy of its assigned values when measured by the target instrument.
- The stability studies (shelf-life, on-board, open-vial) evaluate the calibrator's performance over time without human intervention in the measurement process itself, other than preparing the initial setup and reading the results from the automated Dimension Vista™ System.
- The bottle value assignment process involved "testing N=90 replicates" on "multiple instruments," which demonstrates confidence in the calibrator's performance when used in an automated environment.
So, while not an "algorithm" in the AI sense, the testing conducted is essentially "standalone" in that it verifies the calibrator's properties and its ability to function correctly with the Dimension Vista™ System without requiring human judgment to interpret the calibrator's 'output.'
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the calibrator's values is established through traceability to internationally recognized reference methods and reference laboratories.
- NCEP (National Cholesterol Education Program) reference method for both HDLC and LDLC.
- More specifically for establishment of Master/Anchor Pools:
- Abel-Kendall values for HDL (a CDC reference method).
- Values from reference laboratories (CRMNL) for LDL.
This is a form of "reference measurement procedure" or "primary standard" ground truth, which is the highest level of accuracy for quantitative analytes.
8. The Sample Size for the Training Set
This question is typically for AI algorithms that learn from data. For a calibrator, there isn't a "training set" in the traditional machine learning sense. The material itself is manufactured, and its properties are characterized.
However, if we adapt the concept, the "training" for the assignment curve of the Master Pool/Anchor Pool would involve the collection of "human HDL serum samples with Abel-Kendall values" and "LDL human serum pools with values from reference laboratories (CRMNL)." The document does not specify the sample size of these reference samples used to create the initial standard curves for the Master/Anchor Pools.
9. How the Ground Truth for the Training Set Was Established
As noted above, for a calibrator, "ground truth" is typically its assigned value based on highly accurate reference methods.
- Ground truth for the HDL Master Pool was established using human HDL serum samples with Abel-Kendall values. The Abel-Kendall method is a CDC reference method, considered the "ground truth" standard for HDL-C measurement.
- Ground truth for the LDL Anchor Pool was established using LDL human serum pools with values from reference laboratories (CRMNL). These reference labs adhere to highly stringent methods, representing the "ground truth" for LDL-C.
These reference values are then used to "produce a standard curve for the assignment" of the respective Master/Anchor Pools.
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AUG 1 1 2006
510(k) Summary for the Dimension Vista™ System Lipid Calibrator (LIPID CAL - KC220)
A. 510(k) Number:
| B. Analytes: | High density lipoprotein cholesterol (HDLC) and low densitycholesterol lipoprotein (LDLC). |
|---|---|
| C. Type of Test: | Calibrator Material |
| D. Applicant: | Dade Behring Inc., P.O. Box 6101, Newark, DE 19714-6101Victor M. Carrio, Regulatory Affairs and Compliance ManagerOffice: (302) 631-0376 Fax: (302) 631-6299 |
E. Proprietary and Established Names:
Dimension Vista™ System Lipid Calibrator (LIPID CAL - KC220)
F. Regulatory Information:
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- Regulation section: 21 CFR § 862-1150 Calibrator
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- Classification: Class II
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- Product Code: JIX Calibrator, Multi-Analyte Mixture
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- Panel: Clinical Chemistry
- The LIPID CAL is an in vitro diagnostic product for the calibration G. Intended Use: of high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) methods on the Dimension Vista™ System.
H. Device Description:
LIPID CAL is a liquid, multi-analyte, human albumin based product containing human lipoproteins and bovine gamma globulins. The kit consists of six vials, three vials of Calibrator A, and three vials of Calibrator B which are ready for use (no preparation is required). The volume per vial is 1.5 mL.
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| Item | Device | Predicates | Predicates |
|---|---|---|---|
| Dimension Vista™ SystemLipid Calibrator | Dimension® HDL CalibratorK983850 | Dimension® ALDL CalibratorK020723 | |
| Intended Use | The LIPID CAL is an in vitrodiagnostic product for the calibrationof high density lipoprotein cholesterol(HDLC) and low density lipoproteincholesterol (LDLC) methods on theDimension Vista™ System. | The HDL Cholesterol Calibrator is an in vitrodiagnostic product to be used to calibrate theDimension® clinical chemistry system for theHDL Cholesterol (HDL) method. | The ALDL Calibrator is an in vitro diagnosticproduct intended to be used to calibrate theautomated LDL (ALDL) method for theDimension® clinical chemistry system. |
| Analytes | High density lipoprotein cholesteroland low density lipoproteincholesterol. | High density lipoprotein cholesterol. | Low density lipoprotein cholesterol. |
| Form | Liquid. | Liquid. | Lyophilized. |
| Traceability | National Cholesterol EducationProgram (NCEP) reference method. | NBS SRM 911 a. | NCEP beta-quantification reference method forLDL-C b. |
| Matrix | Human albumin based productcontaining human lipoproteins andbovine gamma globulins. | Stabilized aqueous solution containingcholesterol. | Lyophilized buffered bovine serum albumin-based product supplemented with human lowdensity lipoprotein cholesterol. |
| Number ofLevels | Two levels. | Three levels. | Three levels. |
a - NBS-SRM: National Bereau of Standards - Standard Reference Material.
b -- NCEP - National Cholesterol Education Program
- B. EDXA
- C. Optical Microscopy
- D. X-Ray Diffraction
- E. Thermogravimetric Analysis, Differential Scanning Calorimetry
- F. Brunauer-Emmett-Teller (BET) N2 Adsorption
:
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J. Standard/Guidance Document Referenced:
medical devices
| 1. Guidance: | Guidance for Industry - Abbreviated 510(k) Submissions for InVitro Diagnostic Calibrators; Final, 02/22/1999Guidance for Industry and FDA Staff - Use of Symbols on Labelsand in Labeling of In Vitro Diagnostic Devices Intended forProfessional Use, 11/30/2004 |
|---|---|
| 2. Standards: | CEN 13640 Stability testing of In-Vitro Diagnostic DevicesISO 14971:2000 Medical devices -Application of risk management to |
K. Performance Characteristics:
| 1. Stability: | Target shelf life for the Dimension Vista™ Lipid Calibrator is 12 months. Calibrator shelf life is determined by comparing results of the product stored at 4°C with control stored at -20°C. The method is calibrated from this stored material. The 4°C material values are recovered versus the calibration. Recovery versus time is monitored and percent change over time is determined. Percent change should be less than or equal to 3%. Shelf-life stability (expiration) dating assignment at commercialization reflects the real-time data on file at Dade Behring, Inc. A vial punctured by the instrument and stored on board has a seven day claim. An open vial not stored on board of instrument, but recapped and stored in a refrigerator has a stability claim of 30 days. For testing, vials are opened /punctured on day zero. A quantity sufficient for multiple calibrations is removed and the vials are recapped and stored at 2 - 8 °C. Opened/punctured vials are tested on days 8, 15, 22, and 32 versus freshly opened vials. |
|---|---|
| 2. Traceability: | The assigned values of the Dimension Vista™ Lipid Calibrator are |
| Constituent | Traceability |
|---|---|
| HDLC | National Cholesterol Education Program (NCEP)reference method |
| LDLC | National Cholesterol Education Program (NCEP)reference method |
standardized to the enclosed table of assigned values:
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3. Bottle Value Assignment:
Human HDL (bovine based) and LDL (human serum based) are weighed protein containing solutions. The HDL Master Pool and the LDL Anchor Pool are stored at -70 °C.
HDL human serum samples with Abel-Kendall values are used to produce a standard curve for the assignment of the Master Pool. LDL human serum pools with values from reference laboratories (CRMNL) are used to produce a standard curve for assignment of the Anchor Pool.
The commercial lot is made by adding human HDL and LDL to base matrix in appropriate concentrations for upper calibrator levels. The concentration of each level is verified by using an instrument calibrated with the Master Pool / Anchor Pools. The final bottle values for each level of the commercial lot is assigned and verified using multiple instruments by testing N = 90 replicates.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/4/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 an abstract symbol resembling an eagle or bird-like figure.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Victor M. Carrio RA/QS Compliance Manager Dade Behring, Inc. 500 GBC Dr. PO Box 6101, M/S 514 Newark, DE 19714-6101
AUG 1 1 2006
Re: K061750
Trade/Device Name: Dimension Vista™ Lipid Calibrator (KC220) Regulation Number: 21 CFR§862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIX Dated: June 30, 2006 Received: June 21, 2006
Dear Mr. Carrio:
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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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) 276-0484. 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/industry/support/index.html.
Sincerely yours,
Alberto G
Alberto Gutierrez, Ph.D. 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 Statement
Kolo 1750 510(k) Number (if known):
Device Name:
Dimension Vista™ Lipid Calibrator (KC220)
Indications for Use:
The LIPID CAL is an in vitro diagnostic product for the calibration of high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) methods on the Dimension Vista™ System.
Prescription Use (Per 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 Vitro Diagnostic Devices (OIVD)
CFC
K061750
§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.