ALP IFCC Gen.2 is an in vitro test intended for the quantitative determination of the catalytic activity of alkaline phosphatase in human serum and plasma on COBAS INTEGRA systems. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Device Description

The Roche ALP IFCC Gen.2 assay provides quantitative measurement of the catalytic activity of alkaline phosphatase in human serum and plasma in accordance with a standardized method.. The reagents are packaged in a cassette with two bottles labeled with their instrument positioning, R1 (position B) and SR (position C).

In the presence of magnesium and zinc ions, p-nitrophenyl phosphate is cleaved by phosphatases into phosphate and p-nitrophenol. The p-nitrophenol released is directly proportional to the catalytic ALP activity. It is determined by measuring the increase in absorbance.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study information:

This document is a 510(k) summary for a diagnostic assay, not an AI/ML device. Therefore, many of the typical questions for AI/ML studies (like MRMC studies, reader performance, training set details, etc.) are not applicable here. The acceptance criteria and performance are for an in vitro diagnostic (IVD) reagent and its analytical performance.

1. Table of Acceptance Criteria and Reported Device Performance

The document describes modifications to an existing device (ALP IFCC Gen.2). The acceptance criteria are implicit in the "Pass/Fail criteria" for the verification and validation tests performed. The "reported device performance" refers to the characteristics of the modified device and the confirmation that it met these criteria.

Performance Characteristic	Acceptance Criterion (Implicit)	Reported Device Performance (Modified ALP IFCC Gen.2)
Measuring Range	3.0 - 1200 U/L (consistent with predicate/intended use)	3.0 - 1200 U/L
Lower Detection Limit (LDL)	3.0 U/L (consistent with predicate/intended use)	3.0 U/L
Precision	"See predicate method sheet" (implies performance is comparable)	"Same" as predicate (meaning performance met the established precision specifications for the predicate)
Method Comparison	"See predicate method sheet" (implies performance is comparable)	"Same" as predicate (meaning the method comparison with established methods yielded comparable results to the predicate, likely within established statistical agreement limits)
Interference: Hemolysis	No significant interference up to 0.16 mmol/L (2.5 g/L) hemoglobin	No significant interference up to hemoglobin level of 0.16 mmol/L (2.5 g/L).
Interference: Icterus	No significant interference up to specified I index levels	No significant interference up to an I index of 42 for conjugated bilirubin and 60 for unconjugated bilirubin. (This is an improvement/addition to the predicate which simply stated "No significant interference.")
Interference: Lipemia	No significant interference up to specified L index levels	No significant interference up to an L index of 2000. (This is an improvement/addition to the predicate which simply stated "No significant interference.")
Traceability/Standardization	Standardized against the IFCC (2011) reference procedure	Standardized against the IFCC (2011) procedure. (This is the primary change and was successfully implemented.)
Recovery in Controls	Met pre-determined Pass/Fail criteria for accuracy	Passed all tests based on pre-determined Pass/Fail criteria (specific values not provided, but implies recovery was within acceptable limits for various control levels across the measuring range).
Linearity	Met pre-determined Pass/Fail criteria for linearity across range	Passed all tests based on pre-determined Pass/Fail criteria (specific values not provided, but implies the assay demonstrated linear response across its measuring range within acceptable deviations).

Summary of the Study:

The document describes a Special 510(k) Premarket Notification for modifications to an existing in vitro diagnostic device, ALP IFCC Gen.2. The core purpose was to change the traceability standard of the assay and add specific interference claims. The "study" refers to the verification, validation, and testing activities conducted to confirm that these modifications did not adversely affect the device's performance and that the new claims were supported.

Breakdown of Information Request:

Table of acceptance criteria and reported device performance: See table above.
Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective):
- Sample Size: Not explicitly stated. The document mentions "verification, validation and testing activities" including "recovery in controls, linearity, method comparison, within run precision and interference characteristics." For these types of analytical studies, samples typically include:
  - Controls: Multiple replicates, often 2-3 levels, run over several days/runs for precision and recovery.
  - Linearity samples: A series of diluted or spiked samples across the measuring range.
  - Method Comparison samples: A set of patient samples (often 40-100+) covering the assay range, compared against a reference method or the predicate device.
  - Interference samples: Patient samples or spiked samples tested with various concentrations of interferents (hemoglobin, bilirubin, lipids).
- Data Provenance: Not explicitly stated, but standard practice for Roche Diagnostics (a global company with manufacturing in Germany and operations in the US) would be internal lab testing, likely at their R&D facilities in Germany or the US. It would be prospective testing of the modified 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):
- This question is not applicable in the context of an IVD reagent analytical performance study. "Ground truth" for an IVD assay's performance would be established by:
  - Highly accurate reference measurement procedures (e.g., the IFCC (2011) reference method cited for traceability).
  - Certified reference materials.
  - Comparison against a legally marketed predicate device or a clinical laboratory's established, validated method.
- No "experts" in the sense of clinical reviewers are typically used to establish ground truth for analytical performance, but rather highly skilled laboratory scientists and metrologists ensure the accuracy of the reference methods and measurements.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- This question is not applicable. Adjudication methods like "2+1" or "3+1" are characteristic of clinical studies involving human interpretation (e.g., image reading), where disagreements among reviewers need resolution. This document describes analytical performance testing of a reagent where results are quantitative and objective.
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 is not applicable. An MRMC study assesses the performance of human readers, often with and without AI assistance, on a set of cases. This document is about the analytical performance of an in vitro diagnostic reagent, not an AI/ML device or human reader performance.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- This is not applicable. The device is an in vitro diagnostic reagent executed on an automated instrument (COBAS INTEGRA systems). Its performance is inherently "standalone" in functionality (it performs the assay automatically), but it's not an algorithm in the AI/ML sense that would have an "algorithm only" performance study. Its performance is the instrument's performance running the reagent.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For this type of analytical IVD study, the "ground truth" for method comparison and traceability would be:
  - Reference Measurement Procedures: Specifically, the modified IFCC (2011) reference method for ALP activity.
  - Certified Reference Materials/Calibrators: These provide established, highly accurate values.
  - Comparison to Predicate Device: The performance of the modified device was compared to the legally marketed predicate, which itself would have been validated against established clinical laboratory methods or reference methods.
The sample size for the training set:
- This is not applicable. This is an IVD reagent, not an AI/ML algorithm that requires a "training set." The reagent's formulation and associated analytical procedures are developed through biochemical and analytical chemistry principles, not machine learning training.
How the ground truth for the training set was established:
- This is not applicable for the same reason as point 8.

Summary

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

May 10, 2017

ROCHE DIAGNOSTICS OPERATIONS (RDO) PATRICK STIMART REGULATORY AFFAIRS CONSULTANT 9115 HAGUE ROAD INDIANAPOLIS IN 46250

Re: K171080

Trade/Device Name: ALP IFCC Gen.2 Regulation Number: 21 CFR 862.1050 Regulation Name: Alkaline phosphatase or isoenzymes test system Regulatory Class: II Product Code: CJE Dated: April 10, 2017 Received: April 11, 2017

Dear Patrick Stimart:

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 (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 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 Industry and Consumer Education 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.

Sincerely yours,

Kellie B. Kelm -S

for 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

510(k) Number (if known)

K171080

Device Name ALP IFCC Gen.2

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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ALP IFCC Gen.2 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

In accordance with 21 CFR 807.87. Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification Special 510(k).

The purpose of this Special 510(k) Premarket Notification is to inform FDA of the proposed modifications to the ALP IFCC Gen.2 labeling and provide sufficient detail to support a determination of substantial equivalence. The primary change in traceability from the IFCC method per Tietz , Rinker, Shaw. J Clin Chem Clin Biochem 1983;21:731-748, to the revised IFFC version per Schumann, Klauke, Canalias, et al. Clin Chem Lab Med 2011 Sep;49(9):1439-46.

Other changes which are deemed by Roche not to require premarket notification will also be described.

Note: There were no prior submissions for this device for which FDA provided feedback related to the data or information needed to support substantial equivalence.

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Submitter Name	Roche Diagnostics
Address	9115 Hague RoadP.O. Box 50416Indianapolis, IN 46250-0415
Contact	Primary:Patrick StimartPhone (317) 521-3954FAX (317) 521-2324Email: patrick.stimart@roche.com
	Secondary:Miranda DeverallPhone (317) 521-2897FAX (317) 521-2324Email: miranda.deverall@roche.com
Date Prepared	March 31, 2017
Proprietary Name	ALP IFCC Gen.2
Common Name	ALP2
Classification Name	Alkaline phosphatase or isoenzymes test system(21CFR862.1050, Class 2 device)
Product Codes	CJE
Predicate Devices	The candidate device is a modification of the predicate device. The device name, ALP IFCC Gen.2, is unchanged from how it was cleared in 510(k) K033185.
Establishment Registration	For the ALP IFCC Gen.2, the establishment registration number for Roche Diagnostics GmbH in Mannheim, Germany is 9610126, and for Penzberg, Germany, 9610529. The establishment registration number for Roche Diagnostics in the United States is 1823260.

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1. DEVICE DESCRIPTION

Note: Since ALP IFCC Gen.2 is a reagent, drawings, schematics, illustrations, photos and figures are not pertinent to describe the device and therefore are not present in this submission.

INDICATIONS FOR USE 2.

Note: The intended use of the modified device, as described in its labeling, has not changed as a result of the modification.

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3. TECHNOLOGICAL CHARACTERISTICS

The candidate device, ALP IFCC Gen.2 (ALP2), has been modified from the predicated device with the following changes and additions as described in the candidate assay method sheet.

The traceability of the ALP2 assay was changed from IFCC (1983) reference method to the modified IFCC (2011) reference method, which is noted in the Calibration section of the method sheet.
I index and L index levels for the icterus and lipemia interference claims were added to the Limitations – interference section of the method sheet.

The following tables compare the ALP IFCC Gen.2 with its predicate device, ALP IFCC Gen.2 (K033185).

Feature	Predicate Device ALP IFCC Gen.2(K033185)	Candidate Device ALP IFCCGen.2
Intended use / Indications for use	In vitro test for the quantitativedetermination of the catalytic activity ofalkaline phosphatase (EC 3.1.3.1; ortho-phosphoric monoester phosphohydrolase,alkaline optimum) in serum and plasma onCOBAS INTEGRA systems.	Same
Test principle	Colorimetric assay in accordance with astandardized method.In the presence of magnesium and zinc ions,p-nitrophenyl phosphate is cleaved byphosphatases into phosphate and p-nitrophenol.The p-nitrophenol released is directlyproportional to the catalytic ALP activity. Itis determined by measuring the increase inabsorbance at 409 nm.	Same
Instrument	COBAS INTEGRA 400/700/800	COBAS INTEGRA 400 plus
Sample type	Serum, and Heparin (Li-, Na-, NH4) plasma	same
Calibrator	Calibrator for automated systems (C.f.a.s.)	same
Controls	Precinorm U, Precinorm U plus, PrecipathU, Precipath U plus	Precinorm U, Precinorm U plus,PreciControl ClinChem Multi 1Precipath U, Precipath U plus,PreicControl ClinChem Multi 2

Assay Comparison, General Assay Features Table 1

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Feature	Predicate Device ALP IFCC Gen.2(K033185)	Candidate Device ALP IFCCGen.2
Traceability/Standardization	This method has been standardizedmanually against the original IFCCformulation. (Lit. ref. Tietz 1983)	This method has beenstandardized against the IFCCprocedure. (Lit. ref. Schumann2011)
Reagent stability	Shelf life at 2-8°C: See expiration date oncassetteOn-board in use at 10 to 15°C: 4 weeks	same

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Feature	Predicate Device ALP IFCC Gen.2 (K033185)	Candidate Device ALP IFCC Gen.2
Measuring Range	0- 1200 U/L	3.0- 1200 U/L
Precision	See predicate method sheet	Same
Lower DetectionLimit (LDL)	2 U/L	3.0 U/L
Method Comparison	See predicate method sheet	Same
Limitations -interference	Hemolysis: No significant interference up tohemoglobin level of 0.16 mmol/L (2.5 g/L).Icterus: No significant interference.Lipemia: No significant interference.	Hemolysis: SameIcterus: No significant interference up toan I index of 42 for conjugated bilirubinand 60 for unconjugated bilirubinLipemia: No significant interference upto an L index of 2000.
Expected values	See predicate method sheet	See candidate method sheet. Expectedvalues updated to a more recent literaturereference.

Assay Comparison, Labeled Performance Characteristics Table 2:

4. NON-CLINICAL PERFORMANCE EVALUATION

Based on the risk analysis, the modifications to the ALP IFCC Gen.2 could include potential risks due to the following:

Added specific interference levels for icterus and lipemia, which could cause false (i) ALP values being reported.
(ii) Traceability change for the ALP2 assay could result in inaccurate patient results and the imprecision of the assay.

Verification, validation and testing activities were conducted to establish the performance, which included recovery in controls, linearity, method comparison, within run precision and interference characteristics of the modified device. The device passed all of the tests based on pre-determined Pass/Fail criteria.

5. CONCLUSIONS

The submitted information in this premarket notification supports a substantial equivalence decision. The differences between predicated and candidate do not impact the indications for use or technological characteristics.

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.