THERMO ELECTRON ANGIOTENSIN CONVERTING ENZYME INFINITY (ACE) REAGENT

K041657 · Thermo Electron Corporation · KQN · Aug 30, 2004 · Clinical Chemistry

Device Facts

• Record ID: K041657
• Device Name: THERMO ELECTRON ANGIOTENSIN CONVERTING ENZYME INFINITY (ACE) REAGENT
• Applicant: Thermo Electron Corporation
• Product Code: KQN · Clinical Chemistry
• Decision Date: Aug 30, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1090
• Device Class: Class 2

Indications for Use

The Thermo Electron Infinity™ ACE Reagent Kit is intended for the quantitative determination of ACE in human serum or plasma. The product is for in vitro diagnostic use only. Measurements obtained by this device are used in the diagnosis and treatment of diseases such as sarcoidosis, a disease characterized by the formation of nodules in the lungs, bones, and skin, and Gaucher's disease, a hereditary disorder affecting the spleen. The Thermo Electron Infinity™ ACE Calibrator is intended for the calibration of ACE assays. The product is for in vitro diagnostic use only. The Thermo Electron Infinity™ ACE Normal and Elevated Controls are intended for monitoring the accuracy and precision of ACE assays. The product is for in vitro diagnostic use only.

Device Story

The Thermo Electron Infinity™ ACE Reagent Kit is an in vitro diagnostic system used to measure ACE levels in human serum or plasma. The device is intended for use in clinical laboratory settings by trained laboratory personnel. It utilizes a reagent kit to facilitate the biochemical measurement of ACE, which assists clinicians in diagnosing and monitoring sarcoidosis and Gaucher's disease. The system includes a calibrator for assay standardization and normal/elevated controls to ensure analytical accuracy and precision. Results are provided to healthcare providers to inform clinical decision-making regarding patient disease status and treatment efficacy.

Clinical Evidence

Bench testing only. Precision evaluated per NCCLS EP-5 (N=80 per level; CV 2.3-10.8%). Linearity established 1-120 U/L. Analytical sensitivity 1.0 U/L. Interference testing showed no impact from hemoglobin, bilirubin, or triglycerides; EDTA inhibits assay. Method comparison (N=108) vs. predicate showed r=0.98, slope=0.961. Matrix equivalence confirmed for serum and heparinized plasma.

Technological Characteristics

Quantitative immunoassay; active ingredients: N-[3-(2-furyl)-acryloyl]-L-phenyl-alanylglyclglycine (>0.40 mmol/L) and Tris buffer (55 mmol/L). Liquid form. Requires 37°C incubation and 340 nm absorbance detection. Compatible with manual or automated clinical chemistry analyzers. Standard referenced: NCCLS EP5.

Indications for Use

Indicated for the quantitative determination of Angiotensin Converting Enzyme (ACE) in human serum or plasma to aid in the diagnosis and treatment of sarcoidosis and Gaucher's disease.

Regulatory Classification

Identification

An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of angiotensin converting enzyme in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of diseases such as sarcoidosis, a disease characterized by the formation of nodules in the lungs, bones, and skin, and Gaucher's disease, a hereditary disorder affecting the spleen.

Special Controls

*Classification.* Class II (special 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.

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k041657

B. Purpose for Submission:
New Device

C. Analyte:
Angiotensin Converting Enzyme (ACE)

D. Type of Test:
Quantitative Immunoassay

E. Applicant:
Thermo Electron Corporation

F. Proprietary and Established Names:
Thermo Electron Corporation Infinity™ ACE Liquid Stable Reagent (Angiotensin Converting Enzyme)

G. Regulatory Information:
1. Regulation section:
21 CFR § 862.1090 (Angiotensin converting enzyme (A.C.E.) test system.)
21 CFR § 862.1150 (Calibrator)
21 CFR § 862.1660 (Quality control material (assayed and unassayed)
2. Classification:
Class II
Class II
Class I
3. Product Code:
KQN
JIS
JJX

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4. Panel:
Clinical Chemistry

H. Intended Use:

1. Intended use / Indications for Use:

The Thermo Electron Infinity™ ACE Reagent Kit is intended for the quantitative determination of ACE in human serum or plasma. The product is for in vitro diagnostic use only.

Measurements obtained by this device are used in the diagnosis and treatment of diseases such as sarcoidosis, a disease characterized by the formation of nodules in the lungs, bones, and skin, and Gaucher's disease, a hereditary disorder affecting the spleen.

The Thermo Electron Infinity™ ACE Calibrator is intended for the calibration of ACE assays. The product is for in vitro diagnostic use only.

The Thermo Electron Infinity™ ACE Normal and Elevated Controls are intended for monitoring the accuracy and precision of ACE assays. The product is for in vitro diagnostic use only.

2. Special condition for use statement(s):
Prescription Use Only

3. Special instrument Requirements:
This reagent can be adapted for both manual and automated applications. Requirements include a temperature of 37° C and the ability to read the absorbance at 340 nm.

I. Device Description:

The reagent comes in a ready to use liquid form. The active ingredients are N-[3-(2-furyl)-acryloyl]-L-phenyl-alanylglyclglycine (FAPGG) at greater than 0.40 mmol/L and Tris buffer at 55 mmol/L. The reagent also contains non-reactive fillers and stabilizers.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Sigma Diagnostics Angiotensin Converting Enzyme (ACE) Reagent

2. Predicate k number(s):
k854245

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3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Indications for Use | Same | Quantitative Determination of ACE in serum or plasma |
| Methodology | Same | Immunoassay: FAPGG hydrolyzed to FAP (furylacryloylphenylalanine) and glycylglycone |
| Upper Reportable Concentration | Same | 120 U/L |
| Differences | | |
| Item | Device | Predicate |
| Reagent Form | Liquid Ready to Use | Lyophilized |

K. Standard/Guidance Document Referenced (if applicable):

The sponsor referenced NCCLS EP5: Evaluation of Precision Performance of Clinical Chemistry Devices

L. Test Principle:

The assay reaction is based on the method of Holmquist et al. In this method the direct substrate N-[3-(2-furyl)-acryloyl]-L-phenyl-alanylglyclglycine is hydrolyzed to N-[3-(2-furyl)-acryloyl]-L-phenyl-alanine and glycylglycine:

$$
\text{FAPGG} \xrightarrow{\text{ACE}} \text{FAP} + \text{glycylglycine}
$$

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

The sponsor presented the following precision data for the Cobas Mira using NCCLS EP-5 protocol:

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| | | Level I | Level II |
| --- | --- | --- | --- |
| Within run precision | N | 80 | 80 |
| | Mean (U/L) | 35 | 90 |
| | SD (U/L) | 2.4 | 2.0 |
| | CV (%) | 6.9 | 2.3 |
| Total precision | N | 80 | 80 |
| | Mean (U/L) | 35 | 90 |
| | SD (U/L) | 3.7 | 5.1 |
| | CV (%) | 10.8 | 5.7 |

**b. Linearity/assay reportable range:**

Linearity was assessed by preparing a stock solution with an ACE concentration of at least 10% greater than the claimed upper reportable concentration. Dilutions of the stock solution from 0 to 100% are made with saline and analyzed as unknowns and plotted vs. the target concentration. This plot is examined visually for a linear relationship. In addition, the straight line of best fit is drawn through the data points and compared against a polynomial regression curve of best fit. The deviation of the polynomial regression line from the straight line of best fit must be less than 5%. The upper limit of linearity is defined as the concentration at which the polynomial regression curve deviates from the straight line of best fit by 5%. The reportable range was determined to be 1 to 120 U/L.

**c. Traceability, Stability, Expected values (controls, calibrators, or method):**

Calibrators and controls were previously cleared under K930477 and K860453, respectively, and preparation, storage, stability and traceability were addressed in those submissions. In the current submission, the sponsor is relabeling the previously cleared calibrators and controls and reassigning ACE values using the Thermo ACE reagent.

**d. Detection limit:**

The analytical sensitivity of 1.0 U/L was calculated by multiple measurements of a zero concentration sample. The mean and standard deviation of the dataset were calculated, and the analytical sensitivity was defined as the mean concentration plus two standard deviations.

**e. Analytical specificity:**

The sponsor evaluated the effects of hemoglobin, conjugated and unconjugated bilirubin, and triglycerides (Intralipid). No interference was defined as less than +/- 10% deviation from a neat sample. The following compounds showed no interference up to the concentration listed:

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Hemoglobin: 725 mg/dL
Unconjugated Bilirubin: 13 mg/dL
Conjugated Bilirubin: 20 mg/dL
Triglycerides: 1000 mg/dL

EDTA was shown to inhibit ACE. Users are informed in the
Package Insert that EDTA plasma is not an acceptable specimen.

f. Assay cut-off:
N/A

2. Comparison studies:
a. Method comparison with predicate device:
The sponsor compared 108 serum samples using the predicate device and the Thermo ACE reagent. Concentrations ranged from 1 to 114 U/L as measured by the Thermo ACE reagent. Linear regression analysis produced the following data:
Thermo ACE = 0.961 Predicate – 3.3
Correlation Coefficient (r) = 0.98
b. Matrix comparison:
This assay can measure ACE in either serum or heparinized plasma. The sponsor demonstrated equivalence between the two matrices by assaying six paired serum and heparinized samples, ranging in concentration from approximately 20 to 120 U/L. The heparinized samples had a mean % recovery of serum values of 96%.

3. Clinical studies:
a. Clinical sensitivity:
NA
b. Clinical specificity:
NA
c. Other clinical supportive data (when a and b are not applicable):

4. Clinical cut-off:
N/A

5. Expected values/Reference range:
8 – 52 U/L (at 37° C)

N. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.