(75 days)
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.
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.
The provided text describes the Cholinesterase Gen.2 test system, a device for in vitro quantitative determination of cholinesterase catalytic activity. The submission compares this new device to a predicate device (Cholinesterase Test System, K951595) to establish substantial equivalence.
Here's a breakdown of the requested information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The submission primarily focuses on demonstrating substantial equivalence to a predicate device, rather than explicit "acceptance criteria" against pre-defined performance goals for a new medical device. However, performance characteristics are presented, which implicitly serve as the basis for demonstrating equivalence.
| Performance Characteristic | Acceptance Criteria (Implicit - from Predicate Device) | Reported Device Performance (Cholinesterase Gen.2 Test System) |
|---|---|---|
| Measuring Range | 0 - 25000 U/L | 200 - 14000 U/L (Extended range after postdilution: 200 - 28000 U/L) |
| Lower Detection Limit | 4.5 U/L | 200 U/L |
| Within-run Precision (%CV) | 1.0% at 1728 U/L; 0.99% at 9545 U/L | 0.5% at 6374 U/L; 0.6% at 6263 U/L; 0.6% at 6015 U/L |
| Between-run Precision (%CV) | 2.2% at 1728 U/L; 1.8% at 9545 U/L (total CV) | 1.4% at 6374 U/L; 1.1% at 6263 U/L; 0.9% at 6015 U/L |
| Method Comparison (Correlation to Predicate) | (Implied acceptable correlation) | y = Integra Cholinesterase Gen.2; x = Integra cholinesterase (granulate); Passing-Bablok results: y=0.970x + 128. T = 0.967; r = 0.999 |
| Limitations/Interferences | No significant interference from hemolysis, icterus, lipemia; Citrate and fluoride inhibit reaction; Propanolol causes artificially low values; High albumin increases activity. | No significant interference from bilirubin; No significant interference up to H index of 350, L index of 1000; Citrate and fluoride inhibit reaction; No significant interference from tested drugs; Rare cases of monoclonal gammopathy (IgM) may cause unreliable results. |
| Reagent Stability (On board analyzer) | 8 weeks | 4 weeks |
Study Proving Device Meets Acceptance Criteria:
The "study" refers to the entire submission and the performance data presented within it, which are used to show the new device is substantially equivalent to the predicate. The "Method comparison" section specifically details a direct comparison study.
2. Sample size used for the test set and the data provenance
The sample size for the method comparison (test set) is not explicitly stated. The provenance of the data (country of origin, retrospective/prospective) is also not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not applicable and not provided. The study compares the performance of two in vitro diagnostic devices measuring an analyte, not an interpretation of images or clinical diagnoses by human experts.
4. Adjudication method for the test set
This information is not applicable and not provided. The study involves quantitative measurements by automated systems, not subjective assessments requiring adjudication.
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
This information is not applicable. This is an in vitro diagnostic device for quantitative measurement, not an AI-assisted diagnostic imaging device or an interpretation task by human readers.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
The context is an in vitro diagnostic test system, which inherently operates as a standalone algorithm/system to produce a quantitative result. The results are then used by a human clinician for diagnosis and treatment. The performance metrics reported (precision, measuring range, detection limit, method comparison) represent the standalone performance of the Cholinesterase Gen.2 Test System.
7. The type of ground truth used
The "ground truth" for this type of quantitative diagnostic device is established by comparison to a reference method or a legally marketed predicate device, and through fundamental analytical validation methods.
- For Method Comparison: The predicate device ("Integra cholinesterase (granulate)") serves as the comparative standard.
- For Traceability/Standardization: The device is "Standardized against a reference method using a manual application of the butyrylthiocholine/hexacyanoferrate (III) method on a photometer and the published molar absorptivity of hexacyanoferrate (III)." This manual reference method acts as a form of ground truth for calibration and accuracy.
8. The sample size for the training set
This information is not provided. For this type of IVD, a "training set" in the machine learning sense is not typically applicable. Development involves optimizing reagents and analytical conditions, and validation involves characterizing performance.
9. How the ground truth for the training set was established
This information is not applicable as there is no mention of a "training set" in the context of an AI/ML algorithm. The "standardization" and "traceability" sections describe how the device's measurements are referenced to established analytical methodologies.
{0}------------------------------------------------
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 Diagnostics9115 Hague RoadIndianapolis, IN 46250317-521-3723 |
| Contact Person: Theresa M. AmbroseDate Prepared: April 18, 2006 | |
| Device Name | Proprietary name: Cholinesterase Gen.2 test systemCommon name: CholinesteraseClassification 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. |
{1}------------------------------------------------
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 TestSystem | Predicate deviceCholinesterase Test System(K951595) |
|---|---|---|
| Intended Use | for the quantitative determinationof the catalytic activity ofcholinesterase (EC 3.1.1.8;acycholine acylhydrolase) inserum and plasma. | for use on COBAS INTEGRA for thequantitative determination of thecatalytic activity of cholineseterasecholinesterase (EC 3.1.1.8;acycholine acylhydrolase) in serumand plasma. |
| Assay principle | Detection of catalytic activity viaspectrophotometric detection ofproduct. Butyrylthiocholine ishydrolyzed by cholinesterase;product reduces a yellowsubstrate resulting in a colorlessproduct. | Detection of catalytic activity viaspectrophotometric determinationof product. S-butyrlthicholineiodide is hydrolyzed bycholinesterase; product reacts withDTNB resulting in yellow product. |
| Instrument | same | COBAS Integra family of analyzers(Integra 400/ 700/ 800) |
| ReagentStability | • Unopened kit: up to the statedexpiration date at 2-8 °C• On board the analyzer: 4 weeks | • Unopened kit: up to the statedexpiration date at 2-8 °C• On board the analyzer : 8 weeks |
| Reagent format | liquid | granulate |
| Reagentcomposition | R1: Pyrophosphate, PotassiumhexacyanoferrateR2: Butyrlthiocholine, GOOD'sbuffer, stabilizers | R1: Phosphate, DTNB ( 5,5' -dithiobis-2-nitrobenzoateR2: s-butyrlthiocholine iodide |
| Sample type | Same | Human serum and plasma (EDTA,heparin) |
{2}------------------------------------------------
| Traceability/standardization | Standardized against a referencemethod using a manual applicationof the butyrlthiocholine/hexacyanoferrate (III) method on aphotometer and the published molarabsorptivity of hexacyanoferrate(III) | Manually against an internallyprepared reagent. |
|---|---|---|
| ---------------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------------- |
:
Continued on next page
.
:
.
: : :
{3}------------------------------------------------
510(k) Summary, Continued, Continued
・
.
Comparison to predicate (continued)
| Characteristic | Cholinesterase Gen.2 Test System | Predicate deviceCholinesterase Test System(K951595) |
|---|---|---|
| Measuringrange | 200-14000 U/LExtended range after postdilution:200 -28000 U/L | 0-25000 U/L |
| LowerDetection Limit | 200 U/L | 4.5 U/L |
| Within-runprecision(%CV) | • 0.5% at 6374 U/L• 0.6% at 6263 U/L• 0.6% at 6015 U/L | • 1.0% at 1728 U/L• 0.99% at 9545 U/L |
| Between-runprecision(%CV) | • 1.4% at 6374 U/L• 1.1% at 6263 U/L• 0.9% at 6015 U/L | • 2.2% at 1728 U/L• 1.8% at 9545 U/L (total CV) |
| Limitations:interferences | No significant interference frombilirubin.No significant interference up to• H index of 350 (hemoglobin 350mg/dL)• L index of 1000 (lipemia)Citrate and fluoride inhibit thereaction and must not be used.No significant interference fromtested drugs.In rare cases, monoclonalgammopathy, in particular typwIgM (Waldenstrom'smacroglobulinemia) may causeunreliable results.For diagnostic purposes, resultsshould always be assessed inconjunction with the patient'smedical history and other findings. | No significant interference fromhemolysis, icterus, lipemia.Citrate and fluoride inhibit thereaction and must not be used.Propanolol causes artificially lowcholinesterase values at the testedlevel.Pathologically high levels ofalbumin (7 g/dL) increase theapparent cholinesterase activitysignificantly |
| Characteristic | Cholinesterase Gen.2 TestSystem | Predicate deviceCholinesterase Test System(K951595) |
| Expected values | Children, men, women aged 40 ormore: 5320 - 12920 U/LWomen aged 16-39, not pregnant,not using hormonalcontraceptives: 4260-11250Women aged 18-41, pregnant ortaking contraceptives: 3650-9120 U/L | Females 3000 - 103000 U/LMales 3500 - 114000 U/L |
| Methodcomparison | y = Integra Cholinesterase Gen.2x = Integra cholinesterase (granulate)Passing-Bablok results: y=0.970x + 128. T = 0.967; r = 0.999 |
Continued on next page
{4}------------------------------------------------
510(k) Summary, Continued, Continued
Comparison to predicate (continued)
{5}------------------------------------------------
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),
{6}------------------------------------------------
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 (240) 276-0484. 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 (800) 638-2041 or (301) 443-6597 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
{7}------------------------------------------------
Indications for Use
510(k) Number (if known):
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.
Division Sign-Off
Office . ic Device Evalu ...
510(k) K0601093
§ 862.3240 Cholinesterase test system.
(a)
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).(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.