(74 days)
Abbott Lipid Multiconstituent Calibrator is an in vitro diagnostic product intended for the calibration of Abbott Apolipoprotein A1, Apolipoprotein B, HDL-Cholesterol and LDL-Cholesterol assays on the ARCHITECT c8000 clinical chemistry analyzer.
This is an in vitro diagnostic product intended for use as a calibrator in clinical chemistry assays. Lipid Multiconstituent Calibrator (LipidMCC) contains Apolipoprotein A1, Apolipoprotein B. HDL-Cholesterol and LDL-Cholesterol in a lyophilized human serum-based matrix. The concentrations and activities are suitable for calibration of the Abbott ARCHITECT c8000. LipidMCC contains one level of the four analytes in a lyophilized human serum-based matrix.
Here's a breakdown of the acceptance criteria and the study that proves the Lipid Multiconstituent Calibrator (LipidMCC) meets those criteria, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally focused on accuracy and stability, ensuring the calibrator provides reliable measurements for the target analytes over time.
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Value Assignment | ||
| %CV (Master Lot & Test Lot) | ≤ 3% | Not explicitly stated; "The %CV for both lots should be ≤ 3%" implies met. |
| Master Lot Mean Accuracy | Within 3% of its target value | Not explicitly stated; "The mean for the master lot should be within 3% of its target value" implies met. |
| Control Sample Accuracy | Mean concentration for control sample using test calibrator within 5% of master lot mean and within 5% of pre-assigned value. | Not explicitly stated; "Acceptance criteria: the mean concentration for the control sample using the test calibrator must be within 5%..." implies met. |
| Shelf-life Stability | ≤ ± 5% deviation (compared to -80°C stored vials) | Passed criteria of up to ± 5% deviation at all time points, with one exception (Lot 046RDLP at 52 weeks had 6.2% difference for LDL, but all results passed at 56 weeks and all subsequent time points). This supports a 36-month (3 year) shelf-life. |
| Open Vial Stability | ≤ ± 5% deviation (compared to fresh calibrator) | Passed criteria of up to ± 5% deviation for all analytes (HDL, LDL, Apo A1, Apo B) both for 7 and 10 days storage. Supports 7-day open vial stability. |
2. Sample Size Used for the Test Set and Data Provenance
The document describes several distinct "test sets" for different aspects of performance:
- Standardization (HDL & LDL): Human serum samples were analyzed. The exact number of samples is not specified, but it's referred to as a "method comparison study" using an unspecified quantity of "human serum samples."
- Standardization (Apolipoprotein A1 & B): 40 serum samples with assigned reference values were used in a method comparison study to verify the values after calibration with reference materials.
- Value Assignment: For each analyte, 10 replicates of the test calibrator and 10 replicates of the master calibrator lot were tested (5 replicates from each of two vials). "Quality control samples" and "control samples" (typically a previously assigned calibrator lot) were also used, but their exact number isn't specified beyond being "samples."
- Shelf-life Stability: Three lots of calibrator were tested. For each lot, pairs of vials (one from 2-8°C, one from -80°C) were tested at eight designated time points up to 190 weeks.
- Open Vial Stability: Three lots of lyophilized calibrator were tested. For each lot, sets of three vials were used for different storage conditions (7 days at 2-8°C, 10 days at 2-8°C, and opened daily for 10 days).
Data Provenance:
- Human Serum Samples (Standardization): The source of these samples (e.g., country of origin) is not specified. They appear to be retrospective samples used in method comparison studies.
- Calibrator Lots (Value Assignment, Shelf-life, Open Vial Stability): These are internal lots manufactured by Abbott Laboratories.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The concept of "experts" and "ground truth" in this context refers to established reference methods and materials, rather than individual human experts interpreting data like in imaging studies.
- HDL-Cholesterol & LDL-Cholesterol: The "ground truth" was established by the CDC described reference method for determination of HDL/LDL-cholesterol, performed by a CDC-certified CRMLN (Cholesterol Reference Method Laboratory Network) laboratory. This implies adherence to highly standardized and validated laboratory procedures, effectively serving as the gold standard.
- Apolipoprotein A1 & Apolipoprotein B: The "ground truth" was established using WHO/IFCC/CDC reference materials (SP1-01 and SP3-08). The standardization process was conducted by the Northwest Lipid Metabolism and Diabetes Research Laboratories (University of Washington), which is the designated apolipoprotein standardization facility for the CDC Lipid Standardization Program (LSP). This indicates the use of internationally recognized reference materials and highly specialized, accredited laboratories.
The qualifications of the individuals within these certified laboratories are inherent in the certification and recognition of the institutions they belong to. They are implicitly experts in their field.
4. Adjudication Method for the Test Set
The concept of "adjudication" (e.g., 2+1, 3+1) is typically associated with studies where human readers interpret data, and discrepancies need to be resolved. This is not applicable to the analytical performance studies described for this calibrator.
Instead, the "adjudication" or decision-making process here relies on:
- Comparison to Reference Methods/Materials: Direct comparison of results from the device to established, gold-standard reference methods or materials (e.g., CDC reference methods, WHO/IFCC/CDC reference materials).
- Statistical Analysis: Calculation of bias and percentage deviation, and verification that these fall within predefined acceptance criteria.
- Internal Protocols: The standardization, value assignment, and stability studies followed "procedures approved by Abbott Laboratories, Inc."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for medical devices that involve human interpretation of diagnostic results (e.g., AI-assisted radiology tools) and aims to quantify the improvement in human reader performance with the aid of the device. The LipidMCC is a calibrator, an in-vitro diagnostic product that directly influences the accuracy of an automated analyzer, not a device that assists human readers in interpreting clinical cases.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
This question is not directly applicable in the conventional sense of an "algorithm" performing a diagnostic task without human involvement. LipidMCC is the "standalone" product in question here; it's a calibrator. Its "performance" is its ability to accurately set the measurement scale for an analyzer. The studies conducted (standardization, value assignment, stability) are essentially standalone performance evaluations of the calibrator itself, demonstrating its fitness for purpose without human intervention in the calibration process once the calibrator is used.
7. The Type of Ground Truth Used
The ground truth used is a combination of:
- Reference Methods: Specifically, CDC-described reference methods for HDL- and LDL-cholesterol.
- Reference Materials: WHO/IFCC/CDC reference materials for Apolipoprotein A1 and Apolipoprotein B.
- Assigned Reference Values: For the 40 serum samples used to verify Apolipoprotein A1 and B standardization.
This represents the highest possible standard of analytical truth for these analytes.
8. The Sample Size for the Training Set
The document does not explicitly describe a "training set" in the context of machine learning. The calibrator itself is not an algorithm that is "trained." Instead, the "training" equivalent here refers to:
- Master Calibrator Lot Standardization: This is where the primary values for the master calibrator lot are meticulously established against the foundational reference methods and materials. This process involves multiple measurements and comparisons to ensure accuracy.
- Individual Calibrator Lot Value Assignment: Subsequent production lots of the calibrator are then assigned values based on comparison to the standardized master calibrator lot.
The sample sizes for these processes are described as:
- Standardization (HDL & LDL): "human serum samples" (number not specified).
- Standardization (Apolipoprotein A1 & B): Analysis of the master calibrator lot using WHO/IFCC/CDC reference materials for calibration.
- Value Assignment (Per Lot): 10 replicates of the master calibrator lot, along with 10 replicates of the new test calibrator lot.
9. How the Ground Truth for the Training Set Was Established
As noted above, there isn't a "training set" in the machine learning sense. The "ground truth" for establishing the values of the calibrator itself (especially the master calibrator lot, which serves as the reference for subsequent lots) was established through:
- Direct Analytical Comparison to Gold Standard Reference Methods: For HDL and LDL, this involved method comparison studies against CDC described reference methods performed by a CDC-certified CRMLN laboratory. Bias estimation was used to adjust values to minimize bias to these reference methods.
- Direct Analytical Comparison to Certified Reference Materials: For Apolipoprotein A1 and Apolipoprotein B, this involved calibrating an ARCHITECT c8000 instrument using WHO/IFCC/CDC reference materials and then analyzing the master calibrator lot. The successful completion was documented by certificates from the Northwest Lipid Metabolism and Diabetes Research Laboratories, confirming the traceability to these reference materials.
Essentially, the "ground truth" for the calibrator's values is derived from internationally recognized and highly validated analytical reference standards.
§ 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.