The PATHFAST® CK-MB-11 Calibrators are for calibration of the PATHFAST® system when used for the quantitative determination of creatine kinase-MB in human heparinized or EDTA whole blood and plasma.

Device Description

The PATHFAST CK-MB-II Calibrators are used for calibration of the PATHFAST CK-MB-11 test performed on the PATHFAST instrument. PATHFAST CK-MB-II test is an in vitro diagnostic test for the quantitative measurement of creatine kinase-MB in heparinized or EDTA whole blood and plasma. Currently, PATHAST CK-MB-II Calibrators 1 and 2 are provided as lyophilized products of two vials each. Calibrator 1 consists of saline and a preservative, and Calibrator 2 consists of CK-MB in buffer. Four vials of calibrator diluent also are provided for reconstitution of the calibrators. The diluent consists of an aqueous solution with 0.05% sodium azide. This Special 510(k) is being submitted for a change to a liquid Calibrator 1 formulation and a new dropper bottle container. There are no changes to PATHFAST CK-MB-11 Calibrator 2. As a result of elimination of the reconstitution step for PATHFAST CK-MB-II Calibrator I, the number of bottles of Calibrator Diluent is being reduced from four bottles to two bottles.

AI/ML Overview

The provided document is a 510(k) summary for a PATHFAST® CK-MB-II Calibrator 1, which is a medical device used for the calibration of a system that measures creatine kinase-MB. The 510(k) is a Special 510(k), indicating a modification to an already cleared device, not a new device submission.

The core of this submission is to demonstrate substantial equivalence between a new liquid formulation of Calibrator 1 and its previously cleared lyophilized format. Therefore, the "device performance" in question relates to how well the new formulation maintains the established performance characteristics of the calibrator, rather than the diagnostic performance of the CK-MB-II test itself.

Here's an analysis based on your questions:

1. Table of Acceptance Criteria and Reported Device Performance:

The document broadly states that the modified calibrator met "all pre-established acceptance criteria." However, it does not provide a specific table or detailed quantitative acceptance criteria for each study. It lists the types of studies performed and implies that their results validated the change.

Study Type	Reported Device Performance	Acceptance Criteria (Not Explicitly Stated in Document)
Assay Sensitivity	Met acceptance criteria	Implied: The modified calibrator allows the PATHFAST system to achieve the same sensitivity for CK-MB-II as with the original calibrator. This would likely involve specific limits on detection or quantification of low analyte concentrations.
Limit of Blank (LoB)	Met acceptance criteria	Implied: The LoB for the system, when calibrated with the modified calibrator, falls within acceptable predefined limits. This defines the highest measurement result that is likely to be observed for a blank sample.
Limit of Detection (LoD)	Met acceptance criteria	Implied: The LoD for the system, when calibrated with the modified calibrator, falls within acceptable predefined limits. This defines the lowest concentration of analyte that can be reliably detected.
Limit of Quantitation (LoQ)	Met acceptance criteria	Implied: The LoQ for the system, when calibrated with the modified calibrator, falls within acceptable predefined limits. This defines the lowest concentration of analyte that can be reliably quantified with acceptable accuracy and precision.
Accuracy	Met acceptance criteria	Implied: The modified calibrator allows the PATHFAST system to provide accurate CK-MB-II measurements, comparable to those obtained with the original calibrator. This would likely be assessed against reference materials or established methods.
Method Comparison	Met acceptance criteria	Implied: Results obtained using the PATHFAST system calibrated with the modified liquid calibrator are statistically comparable to results obtained with the system calibrated with the predicate lyophilized calibrator. This often involves correlation coefficients, bias, and agreement studies.
Matrix Comparison	Met acceptance criteria	Implied: The performance of the modified calibrator is consistent across different sample matrices (e.g., heparinized whole blood, EDTA whole blood, plasma), demonstrating no significant matrix effects.
Precision	Met acceptance criteria	Implied: The modified calibrator allows the PATHFAST system to maintain the same level of precision (reproducibility and repeatability) for CK-MB-II measurements as with the original calibrator. This would involve assessment of within-run, between-run, and total precision with specific CV% limits.
Real-time Stability	Met acceptance criteria	Implied: The liquid calibrator maintains its specified performance characteristics (e.g., CK-MB concentration, physical properties) over its labelled shelf-life under specified storage conditions. Specific stability protocols and acceptance limits (e.g., % change from initial value) would be defined.
Elution	Met acceptance criteria	Implied: No significant chemical substances leach from the new polypropylene dropper bottle container into the calibrator solution, which could interfere with the assay or affect calibrator stability. Acceptance criteria would likely involve limits on detected leachables or demonstration of no assay interference.
Evaporation	Met acceptance criteria	Implied: The new polypropylene dropper bottle container adequately prevents evaporation of the calibrator solution over its specified shelf-life, ensuring the concentration remains stable. Acceptance criteria would involve limits on weight loss or concentration change due to evaporation.

2. Sample Size Used for the Test Set and Data Provenance:

The document does not specify the sample sizes used for the test sets in any of the validation/verification studies (e.g., for sensitivity, accuracy, method comparison, stability, etc.).

It also does not directly state the data provenance (e.g., country of origin of the data, retrospective or prospective). Given that the submitting company is "Mitsubishi Chemical Medience Corporation" in "Tokyo, 108-8559 Japan," it is highly probable that the studies were conducted in Japan, but this is not explicitly stated. The studies are described as "validation/verifications studies were performed" which implies prospective testing as part of the design control system for the modified product.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

This question is not applicable to this type of device submission. This document pertains to a calibrator, which is a reagent used to standardize a diagnostic test. The ground truth for a calibrator's performance is typically established through analytical laboratory methods and metrological traceability, not through expert interpretation of images or patient data. The "ground truth" for the calibrator's value would be its assigned concentration based on primary calibrators and validated methods within a quality system, not an expert consensus.

4. Adjudication Method for the Test Set:

This question is not applicable as there is no mention or implication of expert adjudication in the context of validating a calibrator. The validation involves analytical measurements and comparisons against established methods and criteria.

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:

This question is not applicable. An MRMC study is relevant for evaluating the performance of diagnostic imaging aids or AI algorithms that assist human readers in interpreting clinical data. This submission is for a laboratory calibrator, which does not involve human readers interpreting cases or AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:

This question is not applicable. There is no AI algorithm involved in this device (a calibrator). The device's performance is intrinsically standalone in an analytical sense, as it is a chemical reagent, but it's not an "algorithm" operating independently.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):

The "ground truth" for a calibrator like PATHFAST CK-MB-II CALIBRATOR 1 is the analytically assigned value for the analyte concentration (in this case, 0 ng/mL for Calibrator 1, which provides a zero analyte level for the calibration curve). This ground truth is established through:

Primary calibrators and reference materials: Ensuring metrological traceability to international standards if available.
Validated analytical methods: Using highly accurate and precise laboratory techniques to assign the value.
Internal quality control systems: To ensure consistency and accuracy of value assignment.

The document states, "CK-MB concentration = 0 ng/mL. Provides zero analyte level for user calibration curve" for the "Fundamental Scientific Technology" and "Value Assignment" involves "Primary calibrator, master calibrator, stock solution, working calibrator." This indicates an analytical ground truth based on traceable reference materials and meticulous value assignment procedures.

8. The Sample Size for the Training Set:

This question is not applicable. This device is a calibrator, not a machine learning model. Therefore, there is no "training set" in the context of AI or algorithm development. The validation studies performed assess the analytical performance of the calibrator itself.

9. How the Ground Truth for the Training Set was Established:

This question is not applicable for the same reason as point 8; there is no training set for a calibrator.

Summary

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Special 510 (k) - PATHFAST® CK-MB-II Calibrator 1

510(k) SUMMARY

September 4, 2013

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: __k130628

CONTACT:

Judi Smith Precision for Medicine 2 Bethesda Metro Center, Suite 850 Bethesda, MD 20814

PATHFAST CK-MB-II Calibrator 1

on behalf of: Mitsubishi Chemical Medience Corporation 2-8, Shibaura 4-chome, Minato-ku Tokyo, 108-8559 Japan

NAME OF DEVICE: Trade Name:

Common/Classification Names:

Regulation Number:

Product Code:

Class:

PREDICATE DEVICE:

PATHFAST CK-MB-II Calibrator 1 which is supplied with the PATHFAST CK-MB-II Test [K081360, 8/17/2008]

OCT 0 4 2013

DEVICE DESCRIPTION:

INTENDED USE:

The PATHFAST® CK-MB-II Calibrators are for calibration of the PATHFAST® system when used for the quantitative determination of creatine kinase-MB in human heparinized or EDTA whole blood and plasma.

Calibrator

862.1150

JIT

I I

PRODUCT DESCRIPTION:

510(k) Summary-l

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Special 510 (k) - PATHFAST® CK-MB-II Calibrator 1

measurement of creatine kinase-MB in heparinized or EDTA whole blood and plasma.

Currently, PATHAST CK-MB-II Calibrators 1 and 2 are provided as lyophilized products of two vials each. Calibrator 1 consists of saline and a preservative, and Calibrator 2 consists of CK-MB in buffer. Four vials of calibrator diluent also are provided for reconstitution of the calibrators. The diluent consists of an aqueous solution with 0.05% sodium azide. This Special 510(k) is being submitted for a change to a liquid Calibrator 1 formulation and a new dropper bottle container. There are no changes to PATHFAST CK-MB-11 Calibrator 2. As a result of elimination of the reconstitution step for PATHFAST CK-MB-II Calibrator I, the number of bottles of Calibrator Diluent is being reduced from four bottles to two bottles.

SUBSTANTIAL EQUIVALENCE:

The PATHFAST CK-MB-II Calibrator 1 (liquid format) is substantially equivalent to the PATHFAST CK-MB-II Calibrator 1 (lyophilized format) (K081360) in intended use and design. The similarities and differences are listed below.

SIMILARITIES
Item	PATHFAST CK-MB-IICalibrator 1Lyophilized(predicate device)	PATHFAST CK-MB-IICalibrator 1Liquid(Modified)
FDA SubmissionNumber	K081360	K130628
Intended Use	The PATHFAST® CK-MB-11Calibrators are for calibration ofthe PATHFAST® system whenused for the quantitativedetermination of creatine kinase-MB in human heparinized orEDTA whole blood and plasma.	No change
FundamentalScientificTechnology	CK-MB concentration = $0$ng/mL. Provides zero analytelevel for user calibration curve.	No change
ValueAssignment	Primary calibrator, mastercalibrator, stock solution,working calibrator	No change
Instructions	Dispense approximately 100 µLof CAL-1 and CAL-2 in sample	No change

Substantial Equivalence Comparison Table

510(k) Summary-2

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Special 510 (k) – PATHFAST® CK-MB-II Calibrator 1

	wells to load on PATHFAST.
DIFFERENCES
Item	PATHFAST CK-MB-IICalibrator 1Lyophilized(predicate device)	PATHFAST CK-MB-IICalibrator 1Liquid(Modified)
Formulation	Lyophilized MOPS pH7.2.lactose, and enzyme free humanserum, DTT	Liquid saline solution with 0.05%sodium azide as preservative
Format	Lyophilized	Liquid
Calibrator 1Container	Silicon-coated glass bottle withsilicon rubber and plastic screwcap	Polypropylene droplet bottle withhigh density polyethylene nozzleand polypropylene screw cap
CalibratorQuantity	CAL-1 (1mL lyophilized×2vials)CAL-2 (1mL lyophilized×2vials)Calibrator Diluent (1mL×4bottles)	CAL-1 (2mL liquid×1bottle)CAL-2 (1mL-lyophilized ×2vials)(no change)Calibrator Diluent (1mL×2bottles)
Instructions	Reconstitute each vial of CAL-1and CAL-2 with one bottle(1mL) of Calibrator Diluent	Reconstitute CAL-2 with onebottle (1mL) of CalibratorDiluent

As part of the company's Design Control svstem, the following validation/verifications studies were performed.

Formulation: assay sensitivity, Limit of Blank, Limit of Detection, Limit of . Quantitation, accuracy, method comparison, matrix comparison, and precision
. Format: real time stability
Container: elution and evaporation

The results of the validation and verification testing demonstrate that the modified PATHFAST CK-MB-II Calibrator 1 met all pre-established acceptance criteria for the studies identified in the company's design control system Risk Analysis. Therefore, the modified PATHFAST CK-MB-II Calibrator I`is substantially equivalent to the current 510(k)-cleared PATHFAST CK-MB-II Calibrator 1. .

510(k) Summarv-3

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Public Health Service .

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

October 4, 2013

Mitsubishi Chemical Medience Corporation c/o Ms. Judi Smith 2 Bethesda Metro Center, Suite 850 Bethesda, MD 20814

Re: K130628

Trade/Device Name: PATHFAST CK-MB-II CALIBRATORS Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: September 04, 2013 Received: September 05, 2013

Dear Ms. Smith:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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 Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set 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-ા 050.

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Page 2-Ms. Smith

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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/MedicalDevices/ResourcesforYou/Industry/default.htm Also, plaase note the regulation entitled, "Misbranding by reference to premarket notification" (21CFFP Past 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.him 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 no (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Courtney H. Lias, Ph.D.

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use Form

510(k) Number (if known): K130628

Device Name: PATHFAST® CK-MB-II Calibrators

Indication For Use:

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

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

Ruth A. Chesler -S

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

K130628 210(k)

Page I of I

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.