Phenytoin is intended for in vitro diagnostic use in the quantitative determination of the phenytoin concentration in human serum on T60 analyzer. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to help ensure proper therapy.

TDM Calibration set B is intended for in vitro diagnostic use as a calibrator in the quantitative measurement of the kit code 981647 Phenytoin assay on T60 Analyzer.

Device Description

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AI/ML Overview

The provided document describes a 510(k) submission for a Phenytoin test system and a TDM Calibration set B. The submission focuses on demonstrating substantial equivalence to a predicate device rather than presenting a detailed study against specific acceptance criteria. However, we can extract the reported performance of the new device and compare it to the predicate device, which can act as a proxy for acceptance criteria if the aim is to show similar performance.

Here's an analysis based on the provided text, addressing the requested information:

1. A table of acceptance criteria and the reported device performance

Since specific, pre-defined acceptance criteria are not explicitly stated as separate quantifiable thresholds in the document, I will use the predicate device's performance as the benchmark against which the new device's performance is implicitly evaluated for "substantial equivalence." The reported performance of the new device is compared directly to the predicate in "Table 1".

Attribute	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (New Device)
Intended Use	For quantitation of phenytoin in human serum or plasma using automated clinical chemistry analyzers. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels to ensure proper therapy.	For in vitro diagnostic use in the quantitative determination of the phenytoin concentration in human serum on T60 analyzer. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to help ensure proper therapy.
Indication for Use	Same as Intended Use (for predicate).	Phenytoin is intended for quantitative in-vitro diagnostic determination of the phenytoin concentration in human serum using T60 Clinical Chemistry Analyzers. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to help ensure proper therapy.
Assay Protocol	Uses recombinant DNA technology (US Patent no. 4708929) to produce a unique homogeneous enzyme immunoassay system.	Uses recombinant DNA technology (US Patent no. 4708929) to produce a unique homogeneous enzyme immunoassay system.
Traceability/ Standardization	Not explicitly stated (implied to be acceptable for a legally marketed device).	The calibration values are traceable to USP reference materials prepared gravimetrically to drug-free human serum.
Sample Type	Serum or plasma (Na or Li heparin, Na EDTA)	Serum
Reagent Storage	Store CEDIA® Phenytoin II reagents at 2-8 °C. Do not freeze. Refer to box/bottle labels for expiration date.	The unopened reagents are stable at 2...8 °C until the expiration date. DO NOT FREEZE the unopened or reconstituted reagents.
Expected Values	Therapeutic range: 10 - 20 µg/ml for adults, 6 - 14 µg/ml for children.	Therapeutic range for adults: 10 - 20 µg/ml or 40 - 79 µmol/l (1,2)
Instrument	Roche Hitachi 912	T60 and DPC T60i, DPC T60i Kusti
Measuring Range	Between 0.6 µg/ml and ~40 µg/ml (158.4 µmol/l).	0.8 - 38 µg/ml (3.2 – 150 µmol/l)
Precision (Within run - Level 6.3/8.6 µg/ml)	SD = 0.20, CV(%) = 3.2	SD = 0.20, CV(%) = 2.4
Precision (Within run - Level 14.8/20.0 µg/ml)	SD = 0.29, CV(%) = 2.0	SD = 0.32, CV(%) = 1.6
Precision (Within run - Level 26.8 µg/ml)	SD = 0.35, CV(%) = 1.3	N/A (new device reports only two levels)
Precision (Total - Level 6.3/8.6 µg/ml)	SD = 0.32, CV(%) = 5.1	SD = 0.39, CV(%) = 4.5
Precision (Total - Level 14.8/20.0 µg/ml)	SD = 0.46, CV(%) = 3.1	SD = 0.59, CV(%) = 3.0
Precision (Total - Level 26.8 µg/ml)	SD = 0.60, CV(%) = 2.3	N/A (new device reports only two levels)
Method Comparison (Correlation)	$Y=1.00x -0.19$, r = 0.998, Sy.x = 0.39	$y = 1.00x - 0.8$, r = 0.995
Method Comparison (Range/N)	Range 0.7 - 35.1 µg/ml, N = 114	Range 1.3 - 38.3 µg/ml, N = 70
Limitations (Bilirubin)	No significant interference up to I index of 60 (approx. 60 mg/dl).	No interference found up to 58 mg/dl (1000 µmol/l).
Limitations (Hemoglobin)	No significant interference up to H index of 1000 (approx. 1000 mg/dl).	No interference found up to 1000 mg/dl (10 g/l).
Limitations (Lipemia)	No significant interference up to L index of 1000 (approx. 2000 mg/dl Intralipid®).	No interference found up to 1000 mg/dl (10 g/l) of Intralipid®.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Sample Size for Method Comparison (Test Set): 70 samples (N = 70) were used for the new device's method comparison study.
Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Given the submitter's country (Finland), it's possible the data originated there, but this is not confirmed.

3. 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 is a quantitative diagnostic test (immunoassay), not an imaging device requiring expert interpretation. The "ground truth" for such a device is typically established by comparing its results to a well-established reference method (often the predicate device itself, or a gold standard method like mass spectrometry, though not explicitly stated as distinct from the predicate here). Therefore, the concept of "experts" establishing ground truth in the way it applies to image interpretation in radiology is not directly applicable. The predicate device's measurements serve as the comparator.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Adjudication methods (like 2+1 or 3+1) are relevant for studies where human expert disagreement on interpretation is resolved. This is not applicable to a quantitative immunoassay where the comparison is numerical against a reference method. Therefore, the adjudication method is none.

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

No, an MRMC comparative effectiveness study was not done. This type of study (MRMC, human-in-the-loop, AI assistance) is typically performed for image-based diagnostic aids or systems that augment human decision-making. The device described, a Phenytoin assay, is a standalone quantitative chemical analyzer component (reagent system) and does not involve human "readers" in the diagnostic interpretation cycle in the same way an imaging AI would.
Therefore, there is no effect size for human reader improvement with/without AI assistance.

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

Yes, a standalone performance assessment was done. The performance metrics (Measuring Range, Precision, Method Comparison, Limitations) presented are characteristics of the device itself (the Phenytoin assay on the T60 analyzer) operating independently to produce a quantitative result. There is no human intervention in the result generation or interpretation to be removed.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The "ground truth" for the new device's performance was established by comparison to a legally marketed predicate device (CEDIA® Phenytoin II assay). For the method comparison study, the predicate device's results were used as the reference against which the new device's results were correlated. For other performance characteristics like precision, internal validation methods would have been used.

8. The sample size for the training set

The document describes a diagnostic assay, not a machine learning or AI algorithm in the conventional sense that would require a distinct "training set." Therefore, information regarding a "training set sample size" is not applicable to this type of device.

9. How the ground truth for the training set was established

As there is no "training set" in the context of an immunoassay, the concept of establishing ground truth for it is not applicable.

Summary

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510(k) SUMMARY

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: K063145

A. Introduction:

According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

B. Submitter

Thermo Fisher Scientific Oy Ratastie 2 P.O. Box 100 FIN-01621 Vantaa Finland +358 (9) 329 100 tel +358 (9) 3291 0500 fax Contact: Päivi Sormunen, Vice President of QRC Date of Preparation: September 25, 2007

C. Device name

Proprietary name: Phenytoin Common name: Phenytoin Test System Classification: II Class: Toxicology Product Code: DIP

Proprietary name: TDM Calibration set B Common name: Calibrator Classification: II Toxicology Class: Product Code: DKB

Thermo Fisher Scientific Oy

Ratastic 2 P.O. Box 100 FIN-01621 Vantaa Finland

358 (9) 329 100 tel

Y-tunnus 0921547-0 AT No FI09215470 Domicile Helsinki

s w.themo.com

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D. Intended Use

Phenytoin

For in vitro diagnostic use in the quantitative determination of the phenytoin concentration in human serum on T60 analyzer. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to help ensure proper therapy.

TDM Calibration set B

For in vitro diagnostic use as a calibrator in the quantitative measurement of the kit code 981647 Phenytoin assay on T60 Analyzer

Thermo Fisher Scientific Oy

Ratastie 2 P.O. Box 100 FIN-01621 Vantaa Finland

+358 (9) 329 100 tel +358 (9) 3291 0500 fax

Y-tunnus 0921547-0 VAT No F109215470 Domicile Helsinki

www.themo.com

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E. Indications for use

Phenytoin is intended for quantitative in-vitro diagnostic determination of the phenytoin concentration in human serum using T60 Clinical Chemistry Analyzers. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to help ensure proper therapy.

For TDM Calibration set B, see intended use.

F. Substantial Equivalence

Microgenics Corporation item: The CEDIA® Phenytoin II

G. Substantial equivalence -similarities

Phenytoin is substantially equivalent to other devices legally marketed in United States. We claim equivalence to the Microgenics Corporation item, the CEDIA® Phenytoin II

Thermo Fisher Scientific Oy

Ratastie 2 P.O. Box 100 FIN-01621 Vantaa Finland

+358 (9) 329 100 tel +358 (9) 3291 0500 fax

Y-tunnus 0921547-0 VAT No FI09215470 Domicile Helsinki

www.thermo.com

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H. The following table compares the Phenytoin with the predicate assay

Table 1

Phenytoin
Attribute	New device #1	Predicate device #1
Intended Use	For in vitro diagnostic use in thequantitative determination of thephenytoin concentration in humanserum on T60 analyzer.Measurements are used in thediagnosis and treatment of phenytoinoverdose and in monitoring levels ofphenytoin to help ensure propertherapy	The CEDIA® Phenytoin IIhomogeneous enzyme immunoassayis for the quantitation of phenytoinin human serum or plasma usingautomated clinical chemistryanalyzers. Measurements are used inthe diagnosis and treatment ofphenytoin overdose and inmonitoring levels of phenytoin toensure proper therapy.
Indication for Use	Phenytoin is intended for quantitativein-vitro diagnostic determination ofthe phenytoin concentration inhuman serum using T60 ClinicalChemistry Analyzers. Measurementsare used in the diagnosis andtreatment of phenytoin overdose andin monitoring levels of phenytoin tohelp ensure proper therapy.	See Intended Use
Assay Protocol	Assay uses recombinant DNAtechnology (US Patent no. 4708929)to produce a unique homogeneousenzyme immunoassay system.	Assay uses recombinant DNAtechnology (US Patent no. 4708929)to produce a unique homogeneousenzyme immunoassay system.
Traceability/Standardization	The calibration values are traceableto USP reference materials preparedgravimetrically to drug-free humanserum.
Sample Type	Serum	Serum or plasma (Na or Li heparin,Na EDTA)
Reagent Storage	The unopened reagents are stable at2...8 °C until the expiration datestated on the label. Refer to theApplication Notes of your T60analyzer for the on board stabilityof reagents.DO NOT FREEZE the unopenedreagents or the reconstitutedreagents.	Store CEDIA® Phenytoin IIreagents at 2-8 °C. Do not freeze.For stability of the unopenedcomponents refer to the box orbottle labels for the expiration date
Attribute	New device #1	Predicate device #1
Expected Values	Therapeutic range for adults:10 - 20 µg/ml or40 - 79 µmol/l (1,2)	Therapeutic range:10 - 20 µg/ml for adults6 - 14 µg/ml for children
Instrument	T60 and DPC T60i, DPC T60i Kusti	Roche Hitachi 912
Measuring Range	0.8 - 38 µg/ml (3.2 – 150 µmol/l)	Between 0.6 µg/ml and the value ofthe Core TDM Multi-Cal HighCalibrator (approximately 40 µg/mlor 158.4 µmol/l)
Precision	Within runLevel 8.6 µg/mlSD = 0.20CV(%) = 2.4Level 20.0 µg/mlSD = 0.32CV(%) = 1.6Between runLevel 8.6 µg/mlSD = 0.15CV(%) = 1.7Level 20.0 µg/mlSD = 0.23CV(%) = 1.2TotalLevel 8.6 µg/mlSD = 0.39CV(%) = 4.5Level 20.0 µg/mlSD = 0.59CV(%) = 3.0	Within runLevel 6.3 µg/mlSD = 0.20CV(%) = 3.2Level 14.8 µg/mlSD = 0.29CV(%) = 2.0Level 26.8 µg/mlSD = 0.35CV(%) = 1.3TotalLevel 6.3 µg/mlSD = 0.32CV(%) = 5.1Level 14.8 µg/mlSD = 0.46CV(%) = 3.1Level 26.8 µg/mlSD = 0.60CV(%) = 2.3
Method Comparison	(Unit µg/ml)(Deming):$y = 1.00x - 0.8$r = 0.995Range 1.3 - 38.3 µg/mlN = 70	Previous CEDIA® Phenytoinassay (x). Correlation (µg/ml)(Deming's):$Y=1.00x -0.19$r = 0.998Sy.x = 0.39Range 0.7 - 35.1 µg/mlN = 114
Attribute	New device #1	Predicate device #1
Limitations	No interference foundBilirubin:up to 58 mg/dl (1000 $\mu$ mol/l)Hemoglobin:up to 1000 mg/dl (10 g/l)Lipemia:up to 1000 mg/dl (10 g/l) ofIntralipid®	Ikterus:No significant interference frombilirubin up to I index of 60(approximate bilirubinconcentration: 60 mg/dl)Hemolysis:No significant interference fromhemoglobin up to H index of 1000(approximate hemoglobinconcentration: 1000 mg/dl)Lipemia (Intralipid®):No significant interference fromlipemia up to L index of 1000(approximate triglyceridesconcentration: 2000 mg/dl).No significant interference fromtotal protein up to 12 g/dl.No significant interference fromrheumatoid factor up to 100 IU/ml.

Thermo Fisher Scientific Oy

Ratastie 2
P.O. Box 100
FIN-01621 Vantaa
Finland

+358 (9) 329 100 tcl +358 (9) 3291 0500 fax Y-tunnus 0921547-0
VAT No FI09215470
Domicile Helsinki

www.themo.com

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Thermo Fisher Scientific Oy

Ratastie 2
P.O. Box 100
FIN-01621 Vantaa
Finland

+358 (9) 329 100 tel +358 (9) 3291 0500 fax Y-tunnus 0921547-0
VAT No FI09215470
Domicile Helsinki

ww.thermo.com

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nermori SCIENTIFI

Thermo Fisher Scientific Oy

Ratastie 2
P.C). Box 100
FIN-01621 Vantaa
Finland

+358 (9) 329 100 tel +358 (9) 3291 0500 fax Y-tunnus 0921 547-0
VAT No FI09215470 Domicile Helsinki

www.thermo.com

6_Ver08

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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Thermo Fisher Scientific Oy c/o Paivi Sormunen Ratastie 2 P.O. Box 100 FIN-01621 Vantaa Finland

OCT 1 7 2007

K063145 Re: Trade/Device Name: Phentoin, TDM Calibration Set B Regulation Number: 21 CFR 862.3350 Regulation Name: Diphenylhydantoin test system Regulatory Class: Class II Product Code: DIP, DKB Dated: September 25, 2007 Received: September 27, 2007

Dear Ms. Sormunen:

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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Page 2 -

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 (240) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Jean M. Cooper, M.S., D.v.M.

Jean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K063145

Device Names: Phenytoin TDM Calibration set B

Indications for Use:

Phenytoin is intended for quantitative in vitro diagnostic determination of the phenytoin concentration in human serum using T60 Clinical Chemistry Analyzers. Measurements are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to help ensure proper therapy.

TDM Calibration set B is intended for in vitro diagnostic use as a calibrator in the quantitative measurement of the kit code 981647 Phenytoin assay on T60 Analyzer.

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 Diagnostic Device Evaluation and Safety (OIVD)

Signature of CBID, SI

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K063145

Regulation Number and Section

§ 862.3350 Diphenylhydantoin test system.

(a)
Identification. A diphenylhydantoin test system is a device intended to measure diphenylhydantoin, an antiepileptic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of diphenylhydantoin overdose and in monitoring levels of diphenylhydantoin to ensure appropriate therapy.(b)
Classification. Class II.