CHOLINESTERASE GEN.2 TEST SYSTEM

K061093 · Roche Diagnostics Corp. · DIH · Jul 3, 2006 · Clinical Toxicology

Device Facts

• Record ID: K061093
• Device Name: CHOLINESTERASE GEN.2 TEST SYSTEM
• Applicant: Roche Diagnostics Corp.
• Product Code: DIH · Clinical Toxicology
• Decision Date: Jul 3, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3240
• Device Class: Class 1

Intended Use

The Cholinesterase Gen.2 Test System is an in vitro test for the quantitative determination of the catalytic activity of cholinesterase (EC 3.1.1.8; acylcholine acylhydrolase) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of cholinesterase inhibition disorders.

Device Story

In vitro diagnostic test for quantitative determination of cholinesterase catalytic activity in serum and plasma; utilizes butyrylthiocholine method. Principle: cholinesterase hydrolyzes butyrylthiocholine to thiocholine and butyrate; thiocholine reduces yellow hexacyanoferrate III to colorless hexacyanoferrate II. Decrease in color measured spectrophotometrically on COBAS Integra analyzers. Used in clinical laboratory settings by trained technicians. Results interpreted by physicians in conjunction with patient medical history to diagnose and manage cholinesterase inhibition disorders.

Clinical Evidence

Bench testing only. Precision studies (within-run and between-day) performed on Integra 800 analyzer showed CVs ranging from 0.45% to 4.32%. Linearity validated from 200 to 14000 U/L (extended to 28000 U/L). Method comparison against predicate (N=107) yielded correlation coefficients of 0.99. Interference testing confirmed no significant interference (<10%) from common drugs, hemoglobin, bilirubin, or lipemia. No clinical studies were required.

Technological Characteristics

In vitro diagnostic reagent system. Reagents: R1 (Pyrophosphate, Potassium hexacyanoferrate), R2 (Butyrylthiocholine, GOOD's buffer, stabilizers). Sensing principle: spectrophotometric measurement of hexacyanoferrate III reduction. Form factor: liquid reagent for automated COBAS Integra analyzers. Standardized against reference method using manual butyrylthiocholine/hexacyanoferrate III method.

Indications for Use

Indicated for the quantitative determination of cholinesterase catalytic activity in human serum and plasma for the diagnosis and treatment of cholinesterase inhibition disorders. No specific age or gender restrictions provided.

Regulatory Classification

Identification

A cholinesterase test system is a device intended to measure cholinesterase (an enzyme that catalyzes the hydrolysis of acetylcholine to choline) in human specimens. There are two principal types of cholinesterase in human tissues. True cholinesterase is present at nerve endings and in erythrocytes (red blood cells) but is not present in plasma. Pseudo cholinesterase is present in plasma and liver but is not present in erythrocytes. Measurements obtained by this device are used in the diagnosis and treatment of cholinesterase inhibition disorders (e.g., insecticide poisoning and succinylcholine poisoning).

Predicate Devices

• Cholinesterase test system on the Integra Analyzer (k951595)

Submission Summary (Full Text)

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K061093

## 510(k) Summary

JUL - 3 2006

| 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. |
|----------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Submitter name, address, contact | Roche Diagnostics<br>9115 Hague Road<br>Indianapolis, IN 46250<br>317-521-3723 |
| | Contact Person: Theresa M. Ambrose<br>Date Prepared: April 18, 2006 |
| Device Name | Proprietary name: Cholinesterase Gen.2 test system<br>Common name: Cholinesterase<br>Classification name: Cholinesterase test system. |
| Predicate devices | The Cholinesterase Gen.2 test system is substantially equivalent to the currently marketed Cholinesterase Test System cleared under K951595. |
| Device Description | The Cholinesterase Gen.2 Test System is an in vitro test for the quantitative determination of the catalytic activity of cholinesterase in serum and plasma. The test is based on the butyrylthiocholine method. Cholinesterase catalyzes the hydrolysis of butyrylthiocholine to thiocoline and butyrate. Thiocholine reduces the yellow substrate hexacyanoferrate III to the almost colorless hexacyanoferrate II. The decrease in color is measured spectrophotometrically. The calibrator is the Calibrator for automated systems (C.f.a.s; and the recommended control materials are Precinorm U or Precinorm U Plus; and Precipath U or Precipath U plus. |

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### 510(k) Summary, Continued

#### The Cholinesterase Gen.2 Test System is an in vitro test for the quantitative Intended use determination of the catalytic activity of cholinesterase (EC 3.1.1.8; acycholine acylhydrolase) in serum and plasma.

#### Comparison to The below table compares the Cholinesterase Gen.2 Test System with the predicate predicate device, Cholinesterase (K 951595) device

Substantial equivalence: comparison table

| Characteristic | Cholinesterase Gen.2 Test<br>System | Predicate device<br>Cholinesterase Test System<br>(K951595) |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | for the quantitative determination<br>of the catalytic activity of<br>cholinesterase (EC 3.1.1.8;<br>acycholine acylhydrolase) in<br>serum and plasma. | for use on COBAS INTEGRA for the<br>quantitative determination of the<br>catalytic activity of cholineseterase<br>cholinesterase (EC 3.1.1.8;<br>acycholine acylhydrolase) in serum<br>and plasma. |
| Assay principle | Detection of catalytic activity via<br>spectrophotometric detection of<br>product. Butyrylthiocholine is<br>hydrolyzed by cholinesterase;<br>product reduces a yellow<br>substrate resulting in a colorless<br>product. | Detection of catalytic activity via<br>spectrophotometric determination<br>of product. S-butyrlthicholine<br>iodide is hydrolyzed by<br>cholinesterase; product reacts with<br>DTNB resulting in yellow product. |
| Instrument | same | COBAS Integra family of analyzers<br>(Integra 400/ 700/ 800) |
| Reagent<br>Stability | • Unopened kit: up to the stated<br>expiration date at 2-8 °C<br>• On board the analyzer: 4 weeks | • Unopened kit: up to the stated<br>expiration date at 2-8 °C<br>• On board the analyzer : 8 weeks |
| Reagent format | liquid | granulate |
| Reagent<br>composition | R1: Pyrophosphate, Potassium<br>hexacyanoferrate<br>R2: Butyrlthiocholine, GOOD's<br>buffer, stabilizers | R1: Phosphate, DTNB ( 5,5' -<br>dithiobis-2-nitrobenzoate<br>R2: s-butyrlthiocholine iodide |
| Sample type | Same | Human serum and plasma (EDTA,<br>heparin) |

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| Traceability/<br>standardization | Standardized against a reference<br>method using a manual application<br>of the butyrlthiocholine/<br>hexacyanoferrate (III) method on a<br>photometer and the published molar<br>absorptivity of hexacyanoferrate<br>(III) | Manually against an internally<br>prepared reagent. |
|----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------|
|----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------|

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### 510(k) Summary, Continued, Continued

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### Comparison to predicate (continued)

| Characteristic | Cholinesterase Gen.2 Test System | Predicate device<br>Cholinesterase Test System<br>(K951595) |
|-----------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Measuring<br>range | 200-14000 U/L<br>Extended range after postdilution:<br>200 -28000 U/L | 0-25000 U/L |
| Lower<br>Detection Limit | 200 U/L | 4.5 U/L |
| Within-run<br>precision<br>(%CV) | • 0.5% at 6374 U/L<br>• 0.6% at 6263 U/L<br>• 0.6% at 6015 U/L | • 1.0% at 1728 U/L<br>• 0.99% at 9545 U/L |
| Between-run<br>precision<br>(%CV) | • 1.4% at 6374 U/L<br>• 1.1% at 6263 U/L<br>• 0.9% at 6015 U/L | • 2.2% at 1728 U/L<br>• 1.8% at 9545 U/L (total CV) |
| Limitations:<br>interferences | No significant interference from<br>bilirubin.<br><br>No significant interference up to<br>• H index of 350 (hemoglobin 350<br>mg/dL)<br>• L index of 1000 (lipemia)<br><br>Citrate and fluoride inhibit the<br>reaction and must not be used.<br><br>No significant interference from<br>tested drugs.<br><br>In rare cases, monoclonal<br>gammopathy, in particular typw<br>IgM (Waldenstrom's<br>macroglobulinemia) may cause<br>unreliable results.<br><br>For diagnostic purposes, results<br>should always be assessed in<br>conjunction with the patient's<br>medical history and other findings. | No significant interference from<br>hemolysis, icterus, lipemia.<br><br>Citrate and fluoride inhibit the<br>reaction and must not be used.<br><br>Propanolol causes artificially low<br>cholinesterase values at the tested<br>level.<br><br>Pathologically high levels of<br>albumin (7 g/dL) increase the<br>apparent cholinesterase activity<br>significantly |
| Characteristic | Cholinesterase Gen.2 Test<br>System | Predicate device<br>Cholinesterase Test System<br>(K951595) |
| Expected values | Children, men, women aged 40 or<br>more: 5320 - 12920 U/L<br><br>Women aged 16-39, not pregnant,<br>not using hormonal<br>contraceptives: 4260-11250<br><br>Women aged 18-41, pregnant or<br>taking contraceptives: 3650-9120 U/L | Females 3000 - 103000 U/L<br>Males 3500 - 114000 U/L |
| Method<br>comparison | y = Integra Cholinesterase Gen.2<br>x = Integra cholinesterase (granulate)<br><br>Passing-Bablok results: y=0.970x + 128. T = 0.967; r = 0.999 | |

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# 510(k) Summary, Continued, Continued

#### Comparison to predicate (continued)

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the circle is an emblem featuring a stylized eagle with its wings spread, symbolizing the department's mission to protect and promote the health and well-being of the nation.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Theresa M. Ambrose Regulatory Affairs Principal Roche Diagnostics 9115 Hague Road Indianapolis, IN 46250

JUL - 3 2006

Re: k061093

> Trade/Device Name: Cholinesterase Gen.2 Test System Regulation Number: 21 CFR§ 862.3240 Regulation Name: Cholinesterase test system Regulatory Class: Class I Product Code: DIH Dated: April 18, 2006 Received: April 19, 2006

Dear Ms. Ambrose:

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 includions for use stated in the enclosure) to legally marketed predicate devices marked in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendminnts. 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, inting 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 Begistr.

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 your device 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 tollifi the [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Alberto Gutt

Alberto Gutierrez, Ph.D. 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):

K061093

Device Name: Cholinesterase Gen.2

Indications For Use:

The Cholinesterase Gen.2 Test System is an in vitro test for the quantitative determination of the catalytic activity of cholinesterase (EC 3.1.1.8; acylcholine acylhydrolase) in srum and plasma.

Measurements obtained by this device are used in the diagnosis and treatment of cholinesterase inhibition disorders.

Prescription Use XXXX (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

C.C.

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510(k) K0601093