← Product Code [DEM](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEM) · K052819

# VITROS CHEMISTRY PRODUCTS AAT REAGENT, CALIBRATOR KIT 99 AND AAT PERFORMANCE VERIFIERS I, II AND III (K052819)

_Ortho-Clinical Diagnostics, Inc. · DEM · Dec 23, 2005 · Immunology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEM/K052819

## Device Facts

- **Applicant:** Ortho-Clinical Diagnostics, Inc.
- **Product Code:** [DEM](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEM.md)
- **Decision Date:** Dec 23, 2005
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.5130
- **Device Class:** Class 2
- **Review Panel:** Immunology

## Indications for Use

VITROS Chemistry Products AAT Reagent is used to quantitatively measure α1-antitrypsin concentration in human serum. The measurement of α1-antitrypsin in serum aids in the diagnosis of cirrhosis of the liver and pulmonary emphysema. VITROS Chemistry Products Calibrator Kit 99 is used to calibrate VITROS 5, 1 FS Chemistry systems for the quantitative measurement of α1-Antitrypsin (AAT). VITROS Chemistry Products AAT Performance Verifiers are assayed controls used to monitor performance of VITROS AAT Reagents on VITROS 5, 1 FS Chemistry systems.

## Device Story

VITROS Chemistry Products AAT Reagent is an in vitro diagnostic assay for quantitative measurement of alpha-1 antitrypsin (AAT) in human serum. Used on VITROS 5, 1 FS Chemistry systems; device utilizes immunoturbidimetric methodology. System automatically dilutes samples, calibrators, and controls; mixes with polymer-containing buffer and goat antisera specific to human AAT. Resulting antigen/antibody complexes increase solution turbidity, measured spectrophotometrically at 340nm. Turbidity is proportional to AAT concentration. Calibration curve, generated via five-level calibrator kit, allows determination of unknown sample concentrations. Intended for clinical laboratory use to assist in diagnosing liver cirrhosis and pulmonary emphysema.

## Clinical Evidence

Bench testing only. Performance was validated through correlation studies comparing the VITROS AAT assay to the IMMAGE AAT assay using patient samples. Passing & Bablock linear regression analysis yielded y = 0.93x + 2.06 mg/dL. Additional bench testing included evaluation of precision, specificity, expected values, limit of detection, dilution, and specimen matrix effects.

## Technological Characteristics

Quantitative immunoturbidimetric assay. Reagents: dual-chambered liquid (buffer with polymer; goat anti-human AAT antisera). Measurement: spectrophotometric at 340nm. Calibration: 5-level liquid calibrator kit (36-360 mg/dL), traceable to ERM-DA 470. Controls: assayed performance verifiers. Platform: VITROS 5, 1 FS Chemistry systems. Sample matrix: serum.

## Regulatory Identification

An alpha-1-antitrypsin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the alpha-1-antitrypsin (a plasma protein) in serum, other body fluids, and tissues. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition, alpha-1-antitrypsin deficiency has been associated with pulmonary emphysema.

## Predicate Devices

- IMMAGE® Immunochemistry Systems AAT assay ([K964766](/device/K964766.md))
- IMMAGE® Immunochemistry Systems Calibrator 2 ([K973932](/device/K973932.md))
- VITROS Chemistry Products Protein Performance Verifiers I, II & III ([K042477](/device/K042477.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k052819

B. Purpose for Submission:
This is a new device.

C. Measurand:
Alpha-1 Antitrypsin

D. Type of Test:
Quantitative immunoturbidimetric assay

E. Applicant:
Ortho-Clinical Diagnostics, Inc.

F. Proprietary and Established Names:
VITROS Chemistry Products AAT Reagent
VITROS Chemistry Products Calibrator Kit 99
VITROS Chemistry Products AAT Performance Verifiers I, II, and III

G. Regulatory Information:

1. Regulation section:
21CFR§ 866.5130, Alpha-1-antitrypsin Immunological Test System.
21CFR§ 862.1660, Quality Control Material (Assayed and Unassayed)
21CFR§ 862.1150, Calibrator

2. Classification:
Device and calibrator - Class II
Quality control material - Class I

1. Product code:
DEM, Alpha-1-antitrypsin, Antigen, Antiserum, Control
JJX, Single (Specified) Analyte Controls (Assayed and Unassayed)
JIX, Calibrator, Multi-Analyte Mixture

4. Panel:
Immunology (82)
Chemistry (75)

H. Intended Use:

1. Intended use(s):
VITROS Chemistry Products AAT Reagent is used to quantitatively measure $\alpha 1$-antitrypsin concentration in human serum. The measurement of $\alpha 1$-antitrypsin in serum aids in the diagnosis of cirrhosis of the liver and pulmonary emphysema.

VITROS Chemistry Products Calibrator Kit 99 is used to calibrate VITROS 5, 1 FS Chemistry systems for the quantitative measurement of $\alpha 1$-Antitrypsin (AAT).

VITROS Chemistry Products AAT Performance Verifiers are assayed controls used to monitor performance of VITROS AAT Reagents on

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VITROS 5, 1 FS Chemistry systems.

2. Indication(s) for use:
Same as above

3. Special conditions for use statement(s):
For prescription use only.

4. Special instrument requirements:
For use in VITROS 5, 1 FS Chemistry systems (k031924).

I. Device Description:

The VITROS Chemistry Products AAT Reagent is used in conjunction with the VITROS Chemistry Products Calibrator Kit 99 and VITROS Chemistry Products FS Diluent Pack 2 (BSA/Saline) on VITROS 5, 1 FS Chemistry Systems. The VITROS is a dual chambered package containing ready to use liquid reagents: Reagent 1 buffer containing a polymer, and Reagent 2 containing goat antisera to human alpha 1-antitrypsin.

The VITROS Chemistry Products Calibrator Kit 99 is prepared from processed human serum to which inorganic salts, buffers, and preservatives have been added. These standards are used to calibrate VITROS 5, 1 FS Chemistry Systems for the quantitative measurement of AAT. They consist of 5 levels ranging in concentration from 36 to 360 mg/dL.

The VITROS Chemistry Products AAT Performance Verifiers I, II, and III are prepared from processed human serum to which inorganic salts, buffers, and preservatives have been added. These are assayed controls used to monitor the performance of VITROS Chemistry Products AAT Reagent on VITROS 5, 1 FS Chemistry Systems.

The controls and standards are sold separately.

J. Substantial Equivalence Information:

1. Predicate device name(s):
IMMAGE® Immunochemistry Systems AAT Reagent
IMMAGE® Immunochemistry Systems Calibrator 2
VITROS Chemistry Products Protein Performance Verifiers

2. Predicate 510(k) number(s):
k964766
k973932
k042477

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|   | VITROS AAT Assay | IMMAGE AAT Assay  |
|  Intended Use | Quantitative in vitro diagnostic determination of alpha1-antitrypsin | Same  |
|  Sample type | Serum | Same  |

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|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Antibody source | Goat | Same  |
|  Matrix | Performance verifiers prepared from processed human serum to which salts, buffers and preservatives have been added | Same  |
|  Components | Controls and standards are sold separately. | Same  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Methodology | Immunoturbidimetry | Nephelometry  |
|  Calibrator levels | Five levels | Single level  |
|  Calibrator format | Liquid | Lyophilized  |
|  Standardization | BAM-IRMM-LGC (Institute for reference Methods and Materials/Laboratory of the Gov’t Chemist) ERM-DA 470 | International Reference Preparation for Plasma Proteins CRM 470  |
|  QC Material | VITROS AAT Performance verifiers | Two levels of any control material  |

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

None referenced.

# L. Test Principle:

The VITROS AAT Reagent is a dual chambered package containing ready to use liquids. Samples, calibrators, and controls are automatically diluted in saline from VITROS FS Diluent Pack 2 and mixed with Reagent 1 containing a polymer. Addition of antisera specific for human alpha 1-antitrypsin (Reagent 2) produces an immunochemical reaction yielding antigen/antibody complexes. The light scattering properties of the antigen/antibody complexes increase solution turbidity proportional to AAT concentration in the sample. The turbidity is measured spectrophotometrically at  $340\mathrm{nm}$ . Once a calibration has been performed for each reagent lot, the AAT concentration in each unknown sample can be determined using the sorted calibration curve and the measured absorbance obtained in the assay of the sample

# M. Performance Characteristics (if/when applicable):

# 1. Analytical performance:

# a. Precision/Reproducibility:

Within-Day precision was determined using two runs per day with 2 replicates per run. Runs within-day were separated by at least two hours. Within-Lab precision was determined using a single lot of reagents with

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one analyzer and four calibrators.

Additional testing around the low end of the analytical range was performed with 6 replicates per run for 3 days.

|  N | Mean (mg/dL) | Within Day %CV | Within Lab %CV | No. of days | Reps per run  |
| --- | --- | --- | --- | --- | --- |
|  18 | 36.08 | 1.47 | 3.16 | 3 | 6  |
|  18 | 37.56 | 2.66 | 2.66 | 3 | 6  |
|  18 | 29.98 | 1.07 | 2.67 | 3 | 6  |
|  88 | 53.22 | 1.11 | 3.06 | 22 | 2  |
|  88 | 114.75 | 1.18 | 1.34 | 22 | 2  |
|  88 | 262.98 | 1.44 | 3.07 | 22 | 2  |
|  88 | 387.29 | 1.82 | 2.90 | 22 | 2  |

b. Linearity/assay reportable range:

Linearity testing was performed by comparison of the measured with calculated analyte concentration of mixed pools, prepared at concentrations covering the entire assay range. The low pool had an estimated concentration of 25.8 mg/dL. The high pool had an estimated concentration of 499.6 mg/dL. Fifteen levels spanning the assay reportable range were created. Four determinations of each level and each of the three AAT Performance Verifiers were made. Results are shown below. Linearity was set at 30 to 450 mg/dL.

![img-0.jpeg](img-0.jpeg)

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

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The values assigned to the VITROS Chemistry Products Calibrator Kit 99 for AAT are traceable to BAM-IRMM-LGC (Bundesanstalt für Materialforschung und-prüfung/Institute for Reference Methods and Materials/Laboratory of the Gov't Chemist) ERM-DA 470 Reference Material. A five level set of calibrators are prepared and are used to calibrate the Master Lot which is used to assign values to new product lots of the VITROS Chemistry Products AAT Reagent and VITROS Chemistry Products Calibrator Kit 99.

Control values are assigned by running five VITROS Chemistry Systems in five different laboratories. Data was collected over 10 days, 2 runs/day and 2 replicates per run for each performance verifier.

Calibrator Kit Stability – Unopened kit are stable for six months when stored refrigerated at 2°-8°C. Opened vials are stable at ≤3 days when stored capped between 2-8°C.

Performance Verifiers Stability – Unopened kit are stable for six months when stored refrigerated at 2°-8°C. The stability of opened vials stored capped between 2°-8°C is up to 4 weeks.

d. Detection limit:

Detection limit was calculated by running 3 AAT samples with concentrations of 13.1, 15.0, and 16.9 mg/dL. LOD was determined for three reagent lots, run twice per day with 5 replicates per run over 3 days on two VITROS Chemistry systems for a total of 60 replicates. The mean and the standard deviation were calculated. The Detection Limit was found to be 17.3 mg/dL.

The lower end of the linear range was used to determine Limit of quantitation since the limit of detection was determined to be less than the low end of the linear range for all three lots. A limit of quantification is the smallest concentration of unknown that can be reliably be quantified by the instrumental method. The limit of quantitation is established at 30.0 mg/dL.

e. Analytical specificity:

Interference: The substances listed below at the concentrations shown were tested and found not to interfere.

Substances Tested that do not Interfere

|  Compound | Concentration  |
| --- | --- |
|  Acetaminophen | 20 mg/dL  |
|  Acetyl-L-cysteine | 100 mg/dL  |
|  Amoxicillin | 20ug/mL  |
|  Ascorbic acid (L) | 3 mg/dL  |
|  Bilirubin | 60 mg/dL  |
|  Carbamazepine | 120 ug/mL  |
|  Dipyrone | 30 mg/dL  |
|  B-Estradiol | 2.7 mg/dL  |
|  Ethamsylate | 3 mg/dL  |
|  Gentamicin sulfate | 120 ug/mL  |
|  Hemoglobin | 1000 mg/dL  |

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|  Compound | Concentration  |
| --- | --- |
|  Ibuprofen | 400 ug/mL  |
|  Intralipid | 500 mg/dL  |
|  Lidocaine | 60 ug/mL  |
|  Methotrexate | 90.9 mg/dL  |
|  Procainamide | 100 ug/mL  |
|  Propanolol | 5 ug/mL  |
|  Rantidine | 200 ug/mL  |
|  Salicylic acid | 50 mg/dL  |
|  Simvastatin | 16 ug/mL  |
|  Theophylline | 25 mg/dL  |
|  Triglyceride | 1000 mg/dL  |
|  Valproic acid | 500 ug/mL  |

f. Assay cut-off:
Not provided.

2. Comparison studies:

a. Method comparison with predicate device:
A total of 175 human serum samples were assayed using the VITROS AAT assay and its predicate device, IMMAGE AAT assay. Each sample was measured in duplicate on each system. Testing was performed with two lots of VITROS AAT reagents on two VITROS 5, 1 FS Chemistry Systems. There were 97 female patient samples whose age ranged from 23 to 58 years. There were 77 male patient samples whose age ranged from 3 months to 66 years. The results are shown below.

|   | VITROS AAT vs. IMMAGE AAT  |
| --- | --- |
|  Slope | 0.9262 (95% CI: 0.906 to 0.952)  |
|  Intercept | 2.064 (95% CI: -1.698 to 5.37)  |
|  Range (mg/dL) | 30.0 to 450  |
|  r | 0.996  |
|  N | 175  |

b. Matrix comparison:
Serum is the only recommended matrix for this device

3. Clinical studies:

a. Clinical Sensitivity:
Not applicable

b. Clinical specificity:
Not applicable

c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
Reference intervals were determined by testing 145 random specimens from healthy adult subjects. Testing was performed on two VITROS 5, 1 FS

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Chemistry systems. The reference interval based on the study was determined to be 88 to 183 mg/dL.

Each laboratory should establish its own normal ranges since values may differ depending on the population studied.

**N. Proposed Labeling:**
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

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

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**Source:** [https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEM/K052819](https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DEM/K052819)

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