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.

Device Description

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.

AI/ML Overview

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.

Summary

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K123372

510(k) Summary

JAN 14 2013

Submitter's Name/Address Abbott Laboratories 1921 Hurd Drive Irving, TX 75038

Contact Person Linda Morris Senior Regulatory Specialist MS 2-11 Regulatory Affairs (972) 518-6711 Fax (972) 518-6960

Date of Preparation of this Summary: Device Trade or Proprietary Name: Device Common/Usual Name or Classification Name:

January 3, 2013 LibidMCC

Lipid Multiconstituent Calibrator

Classification Number/Class:

Class II / JIX (Calibrator, Multi-Analyte Mixture)

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.

The assigned 510(k) number is:

Test Description:

All human sourced materials were tested and found to be non-reactive for HBsAg, anti-HBc, anti-HCV, HCV RNA or HCV Ag, anti HIV-1/HIV-2, HIV-1 Ag or HIV-2 RNA, anti-HTLV-1/2, and Syphilis by FDA-approved or equivalent methods.

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Substantial Equivalence:

LipidMCC is substantially equivalent to the Apolipoprotein A1/Apolipoprotein B Calibrator (ApoA1/ApoB Calibrator) K983289. These calibrators yield substantially equivalent results on the ARCHITECT c8000 Analyzer. Device similarities and differences are summarized in Table I, Section I of this submission and are listed below:

Similarities:

. Calibrators use pooled human sera with constituents added as required to obtain component levels.
Calibrators contain a single level of each analyte. .
Calibrators are lyophilized and stored at 2 to 8°C until expiration date. .
. Calibrators are used in the calibration of the Apolipoprotein A1, Apolipoprotein B.
Calibrators yield similar results. .

Differences:

. LipidMCC is a single product that contains four analytes for calibration. TheApoA1/ApoB Calibrator is a single product that contains two analytes for calibration.
. LipidMCC is intended to be used to calibrate Apolipoprotein A1, Apolipoprotein B, HDL-Cholesterol and LDL-Cholesterol. ApoA1/ApoB Calibrator is intended for use to calibrate Apolipoprotein A1 and Apolipoprotein B assays only. The ApoA1/B Calibrator does not contain the HDL Cholesterol or LDL Cholesterol components.
The reconstituted ApoA1/ApoB Calibrator is stable for 14 days at 2 to 8℃. ● Reconstituted LipidMCC is stable for 7 days at 2 to 8°C.

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Intended Use:

For use in the calibration of the Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B), Low Density Lipoprotein (LDL), and Ultra High Density Lipoprotein (UHDL) assays on the ARCHITECT c8000 clinical chemistry analyzer.

Performance Characteristics:

The standardization/traceability, value assignment and stability of the Lipid Multiconstituent Calibrator have been validated and verified following procedures approved by Abbott Laboratories, Inc.

A. Standardization/Traceability Information

LipidMCC traceability:

Analyte	Standard Material / Reference Method
HDL-Cholesterol	CDC described reference method for determination ofHDL-cholesterol
LDL-Cholesterol	CDC described reference method for determination ofLDL-cholesterol
Apolipoprotein A1	WHO/IFCC/CDC reference material (SP1-01)
Apolipoprotein B	WHO/IFCC/CDC reference material (SP3-08)

WHO-World Health Organization

IFCC-International Federation of Clinical Chemistry and Laboratory Medicine CDC-Center for Disease Control and Prevention

Standardization Process

A master calibrator lot is used to assign values for each calibrator lot. The master calibrator lot was standardized against the respective reference materials and reference methods listed in the preceding table.

The standardization of the master calibrator lot to the HDL and LDL reference methods was achieved by a method comparison study in which human serum samples were analyzed:

On an ARCHITECT c8000 instrument using the LipidMCC (preliminary . assigned using on-market HDL and LDL Calibrators traceable to the CDC reference methods),

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. Using CDC Reference methods performed by a CDC-certified CRMLN (Cholesterol Reference Method Laboratory Network) laboratory
Bias estimation based on the method comparison results was then used to adjust the LipidMCC HDL and LDL values in order to minimize bias to the respective reference methods.

The standardization of the master calibrator lot to the Apolipoprotein A1 and Apolipoprotein B reference materials was achieved by a protocol and standardization material kit (including the respective WHO/IFCC/CDC reference materials) obtained from the Northwest Lipid Metabolism and Diabetes Research Laboratories (University of Washington). [NOTE: This laboratory is the designated apolipoprotein standardization facility for the CDC Lipid Standardization Program (LSP)].

The standardization was based on calibration of an ARCHITECT c8000 instrument using the respective WHO/IFCC/CDC reference materials and analyzing the concentrations of Apolipoprotein A1 and Apolipoprotein B in the master calibrator lot. These values were then verified by a method comparison study using 40 serum samples with assigned reference values. The successful completion of this standardization process was documented in certificates received from the Northwest Lipid Metabolism and Diabetes Research Laboratories (University of Washington),

B. Value assignment

Value assignment is performed as follows:

. The testing is performed independently for each of the analytes, using one Abbott ARCHITECT c8000.
. For each analyte, the assay is calibrated using the master calibrator lot
System suitability (validity) testing is performed by testing quality control . samples with pre-defined ranges.
Ten replicates of the test calibrator and of the master calibrator lot are tested (the . 10 replicates include five replicates from each of two vials of calibrator).

and

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. The mean analyte values and %CV are calculated for the master lot and for the test calibrator. The %CV for both lots should be ≤ 3%. The mean for the master lot should be within 3% of its target value. If these criteria are met, the mean for the in-process calibrator is the assigned value for this lot.
. The newly assigned values are verified by calibrating the system with both the master calibrator lot and with the newly assigned calibrator, and testing preassigned control samples (typically a previously assigned calibrator lot).
Acceptance criteria: the mean concentration for the control sample using the test . calibrator must be within 5% of the mean concentration using the master lot calibrator and also within 5% of the pre-assigned value.

C. Shelf-life Stability

Testing was performed for three lots of calibrator.

Vials from each lot of the lyophilized calibrator were stored at the designated storage temperature (2 to 8°C) and at -80°C. Pairs of vials (one from each of the two storage conditions) were opened, reconstituted, and tested at eight designated time points up to 190 weeks (3.6 years). Percentage deviations were calculated for the vial stored at 2 to 8°C from the corresponding vial stored at -80°C.

Results:

Results for all three calibrator lots passed the criteria of up to ± 5% deviation at all time points. There was one exception: Lot 046RDLP at 52 weeks, there was 6.2% difference for LDL, but all results passed at 56 weeks and all subsequent time points.

Conclusion:

The shelf-life stability data supports stability of LipidMCC for 190 weeks (3.6 years) at 2 to 8°C. Based on this study, the claimed shelf-life stability is 36 months (3 years).

D. Open Vial Stability

Testing was performed for three lots of lyophilized calibrator.

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Sets of three vials each from each lot of the lyophilized calibrator were opened, reconstituted, and stored for 7 and 10 days at 2 to 8°C. Another set of three vials were reconstituted and opened daily (for 10 days). All stored samples were tested along with a freshly reconstituted calibrator (control) at the beginning and end of the run. Percentage deviations were calculated from the fresh calibrator at the start of the run. Controls were also tested at the start and end of the run and compared to target.

Results for all three calibrator lots passed the criteria of up to ± 5% deviation comparing to the fresh calibrator for all analytes (HDL, LDL, Apo A1, Apo B). LipidMCC is stable for 10 days when stored at 2 to 8°C, reconstituted, and opened daily. Based on this study, the claimed open vial stability at 2 to 8℃ is seven days.

Conclusion:

LipidMCC is substantially equivalent to the Apolipoprotein A1/Apolipoprotein B Calibrator.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

January 14, 2013

Abbott Laboratories c/o Linda Morris 1921 Hurd Dr. Irving, TX 75038

Re: K123372

Trade/Device Name: Lipid Multiconstituent Calibrator (LipidMCC) Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator, Multi-Analyte Mixture Regulatory Class: Class II Product Code: JIX Dated: October 31, 2012 Received: December 4, 2012

Dear Ms. Linda Morris:

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 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

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Page 2 - Linda Morris

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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/cdrh/industry/support/index.html.

Sincerely yours,

Katherine Serrano

For:

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology 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 (if known): K123372

Lipid Multiconstituent Calibrator (LipidMCC) Device Name:

Indications for 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 OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Ruth A. Chesler

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

510(k)__k123372

Regulation Number and Section

§ 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.