PHENOBARBITAL, PHENYTOIN, TDM CALIBRATION SET B AND ABTROL/NORTROL CONTROLS

K063145 · Thermo Electron OY · DIP · Oct 17, 2007 · Clinical Toxicology

Device Facts

• Record ID: K063145
• Device Name: PHENOBARBITAL, PHENYTOIN, TDM CALIBRATION SET B AND ABTROL/NORTROL CONTROLS
• Applicant: Thermo Electron OY
• Product Code: DIP · Clinical Toxicology
• Decision Date: Oct 17, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3350
• Device Class: Class 2

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

Device Story

The T60 Phenytoin Test System is an in vitro diagnostic assay for quantitative measurement of phenytoin in human serum. It utilizes a homogeneous enzyme immunoassay (CEDIA technology) based on bacterial beta-galactosidase. The enzyme is engineered into two inactive fragments that reassociate to form active enzyme; analyte in the patient sample competes with analyte conjugated to an inactive fragment for antibody binding sites. If phenytoin is present, it binds to the antibody, allowing the inactive fragments to reassociate and form active enzyme, which cleaves a substrate to produce a color change measured spectrophotometrically. The absorbance change is directly proportional to the phenytoin concentration. The assay is performed on Siemens T60 Clinical Chemistry Analyzers in a clinical laboratory setting. Results are used by clinicians to monitor therapeutic drug levels and manage phenytoin overdose.

Clinical Evidence

No clinical studies were performed. Substantial equivalence was established through analytical bench testing, including precision (n=84, total CV 3.0-4.5%), linearity (0.8-38.0 μg/mL), analytical specificity (cross-reactivity testing), and method comparison against the predicate (Deming regression slope 1.000, R=0.995).

Technological Characteristics

Homogeneous enzyme immunoassay; recombinant DNA technology (US Patent 4708929). Reagents stable at 2-8°C. Measuring range 0.8-38 µg/ml. Analyzers: T60, DPC T60i. Calibration traceable to USP reference materials.

Indications for Use

Indicated for quantitative in-vitro diagnostic determination of phenytoin concentration in human serum using T60 Clinical Chemistry Analyzers for diagnosis/treatment of phenytoin overdose and monitoring therapeutic levels.

Regulatory Classification

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.

Predicate Devices

• Microgenics CEDIA Phenytoin II Assay (k963840)
• Microgenic CEDIA Core Multi Calibrator (k961659)

Submission Summary (Full Text)

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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 [phone] tel [phone] 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

[phone] tel [phone] 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

[phone] tel [phone] 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 <i>in vitro</i> diagnostic use in the<br>quantitative determination of the<br>phenytoin concentration in human<br>serum on T60 analyzer.<br>Measurements are used in the<br>diagnosis and treatment of phenytoin<br>overdose and in monitoring levels of<br>phenytoin to help ensure proper<br>therapy | The CEDIA® Phenytoin II<br>homogeneous enzyme immunoassay<br>is for the quantitation of phenytoin<br>in human serum or plasma using<br>automated clinical chemistry<br>analyzers. Measurements are used in<br>the diagnosis and treatment of<br>phenytoin overdose and in<br>monitoring levels of phenytoin to<br>ensure proper therapy. |
| Indication for Use | Phenytoin is intended for quantitative<br><i>in-vitro</i> diagnostic determination of<br>the phenytoin concentration in<br>human serum using T60 Clinical<br>Chemistry Analyzers. Measurements<br>are used in the diagnosis and<br>treatment of phenytoin overdose and<br>in monitoring levels of phenytoin to<br>help ensure proper therapy. | See Intended Use |
| Assay Protocol | Assay uses recombinant DNA<br>technology (US Patent no. 4708929)<br>to produce a unique homogeneous<br>enzyme immunoassay system. | Assay uses recombinant DNA<br>technology (US Patent no. 4708929)<br>to produce a unique homogeneous<br>enzyme immunoassay system. |
| Traceability/Standardization | The calibration values are traceable<br>to USP reference materials prepared<br>gravimetrically to drug-free human<br>serum. | |
| Sample Type | Serum | Serum or plasma (Na or Li heparin,<br>Na EDTA) |
| Reagent Storage | The unopened reagents are stable at<br>2...8 °C until the expiration date<br>stated on the label. Refer to the<br>Application Notes of your T60<br>analyzer for the on board stability<br>of reagents.<br>DO NOT FREEZE the unopened<br>reagents or the reconstituted<br>reagents. | Store CEDIA® Phenytoin II<br>reagents at 2-8 °C. Do not freeze.<br>For stability of the unopened<br>components refer to the box or<br>bottle labels for the expiration date |
| Attribute | New device #1 | Predicate device #1 |
| Expected Values | Therapeutic range for adults:<br>10 - 20 µg/ml or<br>40 - 79 µmol/l (1,2) | Therapeutic range:<br>10 - 20 µg/ml for adults<br>6 - 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 of<br>the Core TDM Multi-Cal High<br>Calibrator (approximately 40 µg/ml<br>or 158.4 µmol/l) |
| Precision | Within run<br>Level 8.6 µg/ml<br>SD = 0.20<br>CV(%) = 2.4<br>Level 20.0 µg/ml<br>SD = 0.32<br>CV(%) = 1.6<br>Between run<br>Level 8.6 µg/ml<br>SD = 0.15<br>CV(%) = 1.7<br>Level 20.0 µg/ml<br>SD = 0.23<br>CV(%) = 1.2<br>Total<br>Level 8.6 µg/ml<br>SD = 0.39<br>CV(%) = 4.5<br>Level 20.0 µg/ml<br>SD = 0.59<br>CV(%) = 3.0 | Within run<br>Level 6.3 µg/ml<br>SD = 0.20<br>CV(%) = 3.2<br>Level 14.8 µg/ml<br>SD = 0.29<br>CV(%) = 2.0<br>Level 26.8 µg/ml<br>SD = 0.35<br>CV(%) = 1.3<br>Total<br>Level 6.3 µg/ml<br>SD = 0.32<br>CV(%) = 5.1<br>Level 14.8 µg/ml<br>SD = 0.46<br>CV(%) = 3.1<br>Level 26.8 µg/ml<br>SD = 0.60<br>CV(%) = 2.3 |
| Method Comparison | (Unit µg/ml)<br>(Deming):<br>$y = 1.00x - 0.8$<br>r = 0.995<br>Range 1.3 - 38.3 µg/ml<br>N = 70 | Previous CEDIA® Phenytoin<br>assay (x). Correlation (µg/ml)<br>(Deming's):<br>$Y=1.00x -0.19$<br>r = 0.998<br>Sy.x = 0.39<br>Range 0.7 - 35.1 µg/ml<br>N = 114 |
| Attribute | New device #1 | Predicate device #1 |
| Limitations | No interference found<br>Bilirubin:<br>up to 58 mg/dl (1000 $\mu$ mol/l)<br><br>Hemoglobin:<br>up to 1000 mg/dl (10 g/l)<br><br>Lipemia:<br>up to 1000 mg/dl (10 g/l) of<br>Intralipid® | Ikterus:<br>No significant interference from<br>bilirubin up to I index of 60<br>(approximate bilirubin<br>concentration: 60 mg/dl)<br><br>Hemolysis:<br>No significant interference from<br>hemoglobin up to H index of 1000<br>(approximate hemoglobin<br>concentration: 1000 mg/dl)<br><br>Lipemia (Intralipid®):<br>No significant interference from<br>lipemia up to L index of 1000<br>(approximate triglycerides<br>concentration: 2000 mg/dl).<br><br>No significant interference from<br>total protein up to 12 g/dl.<br>No significant interference from<br>rheumatoid factor up to 100 IU/ml. |

Thermo Fisher Scientific Oy

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

[phone] tcl [phone] 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

:

[phone] tel [phone] 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

[phone] tel [phone] 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 [phone]. 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 [phone] or [phone] 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