COMBITROL TS / AUTOTROL TS assayed controls are intended to be used to monitor and evaluate the analytical performance of the Roche OMNI, alpha series instruments for the analytes listed in the package insert.

As a part of the quality control program in institutions reporting those analytes listed in the package insert, COMBITROL TS and AUTOTROL TS Multi-Analyte Controls should be used in Roche OMNI, alpha series instruments to evaluate test precision and to detect systematic analytical deviations in those laboratories choosing to use a traditional, liquid, quality control product.

Device Description

COMBITROL TS / AUTOTROL TS is a specially formulated aqueous liquid material intended to for use to monitor all analytes measured by the Roche OMNI, alpha series analyzers. It contains a stable suspension of polystyrene microbeads which series and partially absorb red and infrared light similar to erythrocytes, allowing true simulation of the measurement of tHb and SO2 in exactly the same manner as these analytes are determined in whole blood by the Roche OMNI, alpha series analyzers. The three control levels contain three different concentrations of microbeads to simulate low, medium, and high hematocrit blood samples. metobeaus to simulate tons in the provide a convenient method of performing periodic QC checks for laboratories selecting to measure liquid QC material as a part of their quality assurance program.

COMBITROL TS / AUTOTROL TS contain clinically relevant quantities of pH, PCO2, PO2, sodium, potassium, ionized calcium, chloride, lithium, ionized 1 002, 1 02, 80drains) lactate, urea, creatinine and suitable concentrations of microbeads to simulate clinically relevant values of tHb, hematocrit and oxygen saturation.

AI/ML Overview

The provided text does not contain specific acceptance criteria or a detailed study proving that the device meets such criteria in the quantitative sense often associated with AI/ML-driven devices (e.g., sensitivity, specificity, accuracy targets). This document is a 510(k) summary for a medical device cleared in 2001, which predates the widespread use of AI/ML in medical devices and the associated regulatory expectations for performance studies.

Instead, the document focuses on demonstrating substantial equivalence to existing predicate devices. The "study" proving the device meets the acceptance criteria is implicitly the comparison of its characteristics to those of the predicate devices.

Here's an analysis based on the provided text, addressing the points where information is available or inferable:

1. Table of Acceptance Criteria and Reported Device Performance

As mentioned, there are no explicit quantitative acceptance criteria or a performance table in the AI/ML context. The implicit "acceptance criterion" is functional and technological equivalence to predicate devices. The "reported device performance" is a description of its characteristics and intended use, demonstrating this equivalence.

Characteristic	Predicate Devices (COMBITROL PLUS, AVL OPTI-check PLUS)	Modified Device (COMBITROL TS / AUTOTROL TS)	"Acceptance Criteria" Met? (Implicit)
Device Name	COMBITROL PLUS Multi-Analyte Control, AVL OPTI-check PLUS Multi-Analyte Control	COMBITROL TS / AUTOTROL TS Multi Analyte Controls	Yes (Functionally Equivalent)
510(k), Date	K972868, 08/28/97; K913133, 09/27/91; K001632, 06/19/00	N/A (New Device)	N/A
Number of levels	3	3	Yes
Analytes	pH, PCO2, PO2, Na+, K+, Cl-, iCa++, Li+, iMg++, tHb, Hb derivatives, Urea, Glucose, Lactate, Creatinine (for COMBITROL PLUS); pH, PCO2, PO2, Na+, K+, Cl-, iCa++, Urea, Glucose tHb, SO2 (for AVL OPTI-check PLUS)	pH, PCO2, PO2, Na+, K+, Cl-, iCa++, Li+, iMg++, tHb, Hct, SO2, Urea, Glucose, Lactate, Creatinine	Yes (Comparable analytes, expanded for new device)
Container	glass ampoule	glass ampoule	Yes
Fill volume	1.7 mL	1.7 mL	Yes
Color	red (COMBITROL PLUS); milky (AVL OPTI-check PLUS)	milky	Yes (Similar to one predicate)
Matrix	HEPES based aqueous with dyes to simulate Hb and derivatives (COMBITROL PLUS); HEPES based aqueous with polystyrene beads to simulate Hb and SO2 (AVL OPTI-check PLUS)	HEPES based aqueous with polystyrene beads to simulate Hb and SO2	Yes (Similar to one predicate, specifically AVL OPTI-check PLUS)
Intended Use	General control solutions	To monitor and evaluate the analytical performance of the Roche OMNI, alpha series instruments for the analytes listed in the package insert.	Yes (Similar function)
Technological Characteristics	HEMES based aqueous matrix, glass ampoule, 3 levels. Some predicates use dyes, others use polystyrene beads for Hb/SO2 simulation.	HEPES based aqueous matrix, glass ampoule, 3 levels. Uses polystyrene beads to simulate tHb, Hct, SO2.	Yes (Similar to predicate that uses polystyrene beads)

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

This is an in-vitro diagnostic (IVD) control solution, not typically subject to the same "test set" and "data provenance" requirements as AI/ML software. The "testing" involved demonstrating the chemical and physical characteristics of the control solution itself and its behavior in the target instrument.

Test Set Sample Size: Not applicable in the AI/ML sense. The "test" here refers to non-clinical tests (e.g., accelerated aging studies) for stability and formulation comparison against predicate devices. No specific number of "samples" or "cases" for a diagnostic algorithm is mentioned.
Data Provenance: Not applicable for this type of IVD control. The "data" would be analytical measurements from the control solution itself when run on a Roche OMNI, alpha series analyzer.

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

Number of Experts: Not applicable. For IVD control solutions, "ground truth" is typically established by certified reference materials, reference methods, or traceable analytical measurements, not by human expert consensus on images or diagnostic outcomes.
Qualifications of Experts: N/A.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. "Adjudication" is relevant for determining ground truth in ambiguous cases, usually in image interpretation or clinical diagnosis. For a chemical control, the "truth" is determined analytically.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size

MRMC Study: No, an MRMC study was not done. An MRMC study is relevant for AI-assisted diagnostic tools where human readers are interpreting cases. This device is a quality control solution for an instrument.
Effect Size of Human Readers Improvement with AI: Not applicable.

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

Standalone Performance: Not applicable. This device is a consumable control solution, not an algorithm. Its performance is evaluated by how accurately it reflects known analyte concentrations when run on a diagnostic instrument.

7. The Type of Ground Truth Used

Type of Ground Truth: For a multi-analyte control solution, the "ground truth" for the concentrations of the various analytes (pH, PCO2, PO2, Na+, K+, etc.) would be established by reference methods and certified materials, typically calibrated by highly accurate laboratory instruments. For the simulation aspects (tHb, Hct, SO2 using microbeads), the performance is compared against the expected behavior of these analytes in actual blood samples on the target instrument.

8. The Sample Size for the Training Set

Training Set Sample Size: Not applicable. This device does not involve machine learning or a "training set."

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

Ground Truth for Training Set: Not applicable.

Summary of the Study Proving Acceptance Criteria:

The study that "proves the device meets acceptance criteria" is implicitly the submission of non-clinical tests and a comparison to predicate devices.

Non-clinical tests: The document states "Accelerated aging studies on most labile analytes, together with experience with other products with similar formulations support stability claim." These studies would demonstrate that the control solution maintains its specified characteristics over time.
Substantial Equivalence Argument: The core of the 510(k) submission is the detailed comparison of the new device's characteristics (analytes, matrix, levels, container, fill volume, intended use) to those of legally marketed predicate devices. By showing that the COMBITROL TS / AUTOTROL TS is similar in design, materials, and intended use to existing devices, Bionostics, Inc. argues that it is equally safe and effective. The FDA's clearance (K012431) signifies their agreement that this claim of substantial equivalence is met.

In conclusion, the document describes a traditional 510(k) submission for an IVD control solution, where "acceptance criteria" are met by demonstrating substantial equivalence to predicate devices and inherent stability through non-clinical testing, rather than through performance metrics for an AI/ML algorithm.

Summary

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AUG 2 8 2001

Ko 12431

510(k) Summary*

BIONOSTICS

Submitter's name, address (a) (1) Bionostics, Inc. 2 Craig Road Acton, MA 10720
Contact Person Kathleen Storro Director, QA & Regulatory Affairs (978) 263-3856 x 220

Date of preparation of this summary: 27 July 2001

(2) Device trade or proprietary name:
COMBITROL TS and AUTOTROL TS Multi Analyte Controls

Device common or usual name or classification name:

Multi Analyte Control Solution, All Types (Assayed and Unassayed)

PRODUCT NOMENCLATURE	CLASSIFICATIONNUMBER	CLASS	PANEL
MULTI ANALYTE CONTROL SOLUTION	862.1660 75 JJY	I	CHEMISTRY

Substantial Equivalence (3)

COMBITROL TS and AUTOTROL TS Multi Analyte Controls are substantially equivalent in function, safety and efficacy to a number of currently marketed devices known as 'Combi' or 'Multi-Analyte' control solutions. In example:

Comparison of COMBITROL TS / AUTOTROL TS to predicate devices for substantial equivalency

Characteristic	Predicate Devices	Modified Device
Name:	COMBITROL PLUSMulti-Analyte Control	AVL OPTI-check PLUSMulti-Analyte Control	COMBITROL TSAUTOTROL TSMulti Analyte Controls
510(k), Date:	K972868, 08/28/97K913133, 09/27/91	K001632, 06/19/00
Number of levels:	3	3	3
Analytes:	pH, PCO2, PO2, Na+,K+, Cl-, iCa++Li+, iMg++, tHb, Hbderivatives, Urea,Glucose, Lactate,Creatinine	pH, PCO2, PO2, Na+, K+,Cl-, iCa++, Urea, GlucosetHb, SO2	pH, PCO2, PO2, Na+, K+,Cl-, iCa++, Li+, iMg++, tHb,Hct, SO2, Urea, Glucose,Lactate, Creatinine,
Container:	glass ampoule	glass ampoule	glass ampoule
Fill volume:	1.7 mL	1.7 mL	1.7 mL
Color:	red	milky	milky
Matrix:	HEPES based aqueouswith dyes to simulateHb and derivatives	HEPES based aqueouswith polystyrene beads tosimulate Hb and SO2	HEPES based aqueouswith polystyrene beads tosimulate Hb and SO2

This summary of safety and effectiveness is submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

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Description of the new device (4)

Description of the new device
COMBITROL TS / AUTOTROL TS is a specially formulated aqueous liquid material intended to for use to monitor all analytes measured by the Roche OMNI, alpha series analyzers. It contains a stable suspension of polystyrene microbeads which series and partially absorb red and infrared light similar to erythrocytes, allowing true simulation of the measurement of tHb and SO2 in exactly the same manner as these analytes are determined in whole blood by the Roche OMNI, alpha series analyzers. The three control levels contain three different concentrations of microbeads to simulate low, medium, and high hematocrit blood samples. metobeaus to simulate tons in the provide a convenient method of performing periodic QC checks for laboratories selecting to measure liquid QC material as a part of their quality assurance program.

Intended use of the device (5)
COMBITROL TS / AUTOTROL TS assayed controls are intended to be used to Combilition 10 / 110 / 110 / 110 / 110 Roche OMNI, alpha series instruments for the analytes listed in the package insert ..
Technological characteristics of the device. (6)
Technological characteribaTS assayed control is intended to be used to monitor and evaluate the analytical performance of the Roche OMNI, alpha series instruments for the analytes listed in the package insert is technologically equivalent to currently marketed products to which substantial equivalence is claimed. It contains a low concentration, stable suspension of polystyrene microbeads which reflect and partially absorb red and infrared light similar to erythrocytes, allowing true simulation of the measurement of tHb, hematocrit and SO2 in exactly the same manner as these analytes are determined in whole blood by the Roche OMNI, alpha series instruments.
Summary of non-clinical tests submitted with the premarket notification for the (b) (1) device.
Accelerated aging studies on most labile analytes, together with experience with other products with similar formulations support stability claim.
Summary of clinical tests submitted with the premarket notification for the device. (b) (2) N/A
Conclusions drawn from the clinical and non-clinical trials. (b) (3) Comparison of technological characteristics, formulation and intended use to predicate devices listed in this summary support the claim of substantial equivalence.

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Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with three lines representing its wings.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 2 8 2001

Ms. Kathleen Storro Director, QA and Regulatory Affairs Bionostics, Inc. 2 Craig Road Acton, MA 01720

Re: K012431

Trade/Device Name: COMBITROL TS / AUTOTROL TS Multi-Analyte Controls Regulation Number: 21 CFR 862.1660 Regulatory Class: I, reserved Product Code: JJS, JJY Dated: July 27, 2001 Received: July 31, 2001

Dear Ms. Storro:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device mendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include are gone an other 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations (1 recultures) in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such perious on. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and 1 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices ---Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number: K012431

COMBITROL TS / AUTOTROL TS Device Name: Multi-Analyte Controls

For In Vitro Diagnostic Use

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use(Per 21 CFR 801.109)
------------------------------------------	-------------

(Division Sign-Off)	Kesia Alexander for Jan Cooper (Optional Format 1-2-96)
Division of Clinical Laboratory Devices
510(k) Number	K012431

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.