The cassettes COBAS Integra ALP IFCC Gen.2 Small (ALP2S) and COBAS Integra ALP IFCC Gen.2 Large (ALP2L) contain an in vitro diagnostic reagent system intended for use on COBAS Integra systems for the quantitative determination of the catalytic activity of alkaline phosphatase in human serum and plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Device Description

The COBAS Integra ALP IFCC Gen.2 is a colorimetric assay for the determination of the catalytic activity of alkaline phosphatase in serum or plasma in accordance to the recommended reference method of the International Federation of Clinical Chemists (IFCC). In the presence of magnesium and zinc ions, p-nitrophenyl phosphate is cleaved by phosphatases into phosphate and p-nitro-phenol. The p-nitro-phenol released is directly proportional to the catalytic ALP activity.

AI/ML Overview

This is an in vitro diagnostic device for quantitative determination, not an AI/ML device. The request asks for details specific to AI/ML device studies that are not applicable here. However, I can still extract the acceptance criteria and the summary of the study proving the device meets them based on the provided text, focusing on performance characteristics relevant to an IVD.

Here's the summary:

1. Acceptance Criteria and Reported Device Performance:

Acceptance Criteria / Performance Characteristic	Reported Device Performance (COBAS Integra ALP IFCC Gen.2)
Intended Use	Quantitative determination of catalytic activity of alkaline phosphatase in human serum and plasma for diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.
Method	Colorimetric assay in accordance with the recommended reference method of the International Federation of Clinical Chemistry (IFCC).
Sample Type	Serum, Heparin plasma
Measuring Range	2 - 1200 U/L
Expected Values (at 37° C)	Adults: Females: 35 - 104 U/L, Males: 40 - 129 U/L Children: 1 day: < 250 U/L, 2 - 5 days: < 231 U/L, 6 days - 6 months: < 449 U/L, 7 months - 1 year: < 462 U/L, 1 - 3 years: < 281 U/L, 4 - 6 years: < 269 U/L, 7 - 12 years: < 300 U/L, 13 - 17 years (f): < 187 U/L, 13 - 17 years (m): < 390 U/L
Substantial Equivalence	Claims substantial equivalence to the currently marketed COBAS Integra ALP IFCC Assay (K981897).

2. Study that Proves the Device Meets Acceptance Criteria:

The provided document is a 510(k) Summary for a COBAS Integra ALP IFCC Gen.2, an in vitro diagnostic reagent system. The primary method described for demonstrating its meeting of acceptance criteria is a comparison to a legally marketed predicate device to establish substantial equivalence.

Study Type: This is a comparative study against an existing, cleared device (the predicate device: COBAS Integra ALP IFCC Assay, K981897). The intent is to show that the new device performs similarly and is safe and effective as the predicate.
Data Provenance and Sample Size: The document does not explicitly state the sample size used for the comparison or the data provenance (e.g., country of origin, retrospective/prospective). For an IVD, comparison studies typically involve patient samples and/or control materials.
Ground Truth Establishment: The ground truth for such quantitative assays is usually established by a reference method or a calibrated reference material. The document states that the assay is a "colorimetric assay for the determination of the catalytic activity of alkaline phosphatase in serum or plasma in accordance to the recommended reference method of the International Federation of Clinical Chemists (IFCC)." This indicates that the IFCC reference method serves as the ground truth or the standard against which the device's performance is measured.

3. AI/ML Specific Questions (Not Applicable to this Device):

Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience): Not applicable. This is a biochemical assay, not an imaging device requiring expert interpretation. The ground truth is based on a reference standard/method (IFCC).
Adjudication method (e.g. 2+1, 3+1, none) for the test set: Not applicable. Adjudication methods are typically for evaluating subjective interpretations, which is not the case for a quantitative biochemical assay.
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: Not applicable. This device is not an AI-assisted diagnostic tool that involves human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Not applicable. This is a reagent and instrument system, not an algorithm.
The type of ground truth used (expert consensus, pathology, outcomes data, etc): The ground truth is based on the recommended reference method of the International Federation of Clinical Chemists (IFCC) for alkaline phosphatase activity. This would involve specific chemical reactions and measurements rather than expert consensus on subjective findings.
The sample size for the training set: Not applicable. This is not an AI/ML device that requires training data in the conventional sense. Device development would involve optimization and calibration using various samples, but not a "training set" like an AI model.
How the ground truth for the training set was established: Not applicable for the same reason given above. The device's performance is calibrated and validated against established reference methods for the analyte.

Summary

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OCT 1 4 2003

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K033185

510(k) Summary - COBAS Integra ALP IFCC Gen.2

Introduction	According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence
Submittername, address,contact	Roche Diagnostics Corporation9115 Hague RdIndianapolis IN 46250(317) 521-3831Contact person: Sherri L. CoenenDate prepared: September 29, 2003
Device Name	Proprietary name: Roche Diagnostics COBAS Integra ALP IFCC Gen.2Common name: Alkaline phosphatase AssayClassification name: Alkaline phosphatase or isoenzymes test system
Devicedescription	The COBAS Integra ALP IFCC Gen.2 is a colorimetric assay for thedetermination of the catalytic activity of alkaline phosphatase in serum orplasma in accordance to the recommended reference method of theInternational Federation of Clinical Chemists (IFCC). In the presence ofmagnesium and zinc ions, p-nitrophenyl phosphate is cleaved byphosphatases into phosphate and p-nitro-phenol. The p-nitro-phenol releasedis directly proportional to the catalytic ALP activity.
Intended use	The cassettes COBAS Integra ALP IFCC Gen.2 Small (ALP2S) and COBASIntegra ALP IFCC Gen.2 Large (ALP2L) contains an in vitro diagnosticreagent system intended for use on COBAS Integra systems for thequantitative determination of the catalytic activity of alkaline phosphatase inhuman serum and plasma. Measurements of alkaline phosphatase or itsisoenzymes are used in the diagnosis and treatment of liver, bone,parathyroid, and intestinal diseases.

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510(k) Summary - COBAS Integra ALP IFCC Gen.2, continued

PredicateDevice	We claim substantial equivalence to the currently marketed COBAS IntegraALP IFCC Assay. (K981897).
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The following table describes the similarities and differences between the Reagent Summary COBAS Integra ALP IFCC Gen.2 and the predicate device.

Topic	COBAS Integra ALP IFCC(K981897)	COBAS Integra ALP IFCC Gen.2(Modified Device)
Intended Use	The cassettes COBAS Integra ALPIFCC (ALPL2 and ALPL6) containan in vitro diagnostic reagent systemintended for use on COBAS Integrasystems for the quantitativedetermination of the catalytic activityof alkaline phosphatase in serum andplasma.	The cassettes COBAS Integra ALPIFCC Gen.2 Small (ALP2S) andCOBAS Integra ALP IFCC Gen.2Large (ALP2L) contain an in vitrodiagnostic reagent system intendedfor use on COBAS Integra systemsfor the quantitative determination ofthe catalytic activity of alkalinephosphatase in serum and plasma.

Method	colorimetric assay in accordance withthe recommended reference methodof the International Federation ofClinical Chemistry (IFCC)	Same
Sample type	SerumHeparin plasma	Same
Measuringrange	2 - 1500 U/L	2 - 1200 U/L
Expectedvalues	Measured at 37° CAdultsFemales: 35 - 104 U/LMales: 40 - 129 U/LChildren1 day: < 250 U/L2 - 5 days: < 231 U/L6 days - 6 months: < 449 U/L7 months - 1 year: < 462 U/L1 - 3 years: < 281 U/L4 - 6 years: < 269 U/L7 - 12 years: < 300 U/L13 - 17 years (f): < 187 U/L13 - 17 years (m): < 390 U/L	Same

. . .

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Image /page/2/Picture/1 description: The image is a black and white logo for the U.S. Department of Health and Human Services. The logo features the department's name encircling a symbol. The symbol is a stylized representation of three human profiles facing right, with flowing lines above them that could be interpreted as hair or wings. The text is arranged in a circular fashion around the symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 1 4 2003

Ms. Sherri L. Coenen Regulatory Affairs Consultant Regulatory Submissions, Centralized Diagnostics Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250-0457

Re: K033185

Trade/Device Name: COBAS Integra ALP IFCC Gen.2 Regulation Number: 21 CFR 862.1050 Regulation Name: Alkaline phosphatase or isoenzymes test system Regulatory Class: Class II Product Code: CJE Dated: September 29, 2003 Received: October 1, 2003

Dear Ms. Coenen:

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 (301) 594-3084. 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/dsma/dsmamain.html.

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known): N/A

K033185

Device Name: COBAS Integra ALP IFCC Gen.2

Indications For Use:

Carol C. Benam/R. Jean Cooper. DVM
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K033185

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

Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use OR Over-The-Counter Use (Per 21 CFR 801.109)

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1050 Alkaline phosphatase or isoenzymes test system.

(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.