VITROS CHEMISTRY PRODUCTS APOA1 AND APOB REAGENTS, CALIBRATOR KITS 21 AND 22 AND APOA1 AND APOB PERFORMANCE VERIFIERS

K042521 · Ortho-Clinical Diagnostics, Inc. · JIT · Nov 18, 2004 · Clinical Chemistry

Device Facts

• Record ID: K042521
• Device Name: VITROS CHEMISTRY PRODUCTS APOA1 AND APOB REAGENTS, CALIBRATOR KITS 21 AND 22 AND APOA1 AND APOB PERFORMANCE VERIFIERS
• Applicant: Ortho-Clinical Diagnostics, Inc.
• Product Code: JIT · Clinical Chemistry
• Decision Date: Nov 18, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1150
• Device Class: Class 2

Intended Use

For in vitro diagnostic use only. VITROS Chemistry Products ApoA1 Reagent is used to quantitatively measure apolipoprotein A1 (ApoA1) concentration in human serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 21 is used to calibrate VITROS 5.1 FS Chemistry Systems for the quantitative measurement of apolipoprotein A 1 (ApoA1). For in vitro diagnostic use only. VITROS Chemistry Products ApoA1 Performance Verifier I is an assayed controls used to monitor the performance of ApoA1 Reagent on VITROS 5,1 FS Chemistry Systems. For in vitro diagnostic use only. VITROS Chemistry Products ApoB Reagent is used to quantitatively measure apolipoprotein B (ApoB) concentration in human serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 22 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of apolipoprotein B (ApoB). For in vitro diagnostic use only. VITROS Chemistry Products ApoB Performance Verifier I is an assayed controls used to monitor the performance of ApoB Reagent on VITROS 5,1 FS Chemistry Systems.

Device Story

VITROS Chemistry Products ApoA1/ApoB reagents are liquid-based assays for use on the VITROS 5,1 FS Chemistry System; an automated clinical chemistry analyzer. System combines reagents with human serum/plasma samples to perform immunoturbidimetric assays. Instrumentation automates reagent handling and measurement. Results are provided to clinicians to aid in diagnosing/treating lipid disorders, atherosclerosis, and liver/renal diseases. Performance is monitored using assayed controls (Performance Verifiers I). System is intended for professional use in clinical laboratory settings.

Clinical Evidence

Bench testing only. Precision evaluated per NCCLS EP5-A (Within-Lab CV% 1.8-3.9%). Linearity/recovery evaluated per NCCLS EP6-A (recovery 91.3-108.8%). Analytical specificity confirmed for triglycerides, bilirubin, hemoglobin, and ascorbic acid. Method comparison (n=136-137) against predicate showed slopes of 0.98-1.00 and correlation coefficients of 0.985-0.987. Reference ranges established per NCCLS C28A using 121 healthy subjects.

Technological Characteristics

Immunoturbidimetric assay; dual-chambered liquid reagents; spectrophotometric detection at 340 nm. Calibrators/verifiers consist of processed human serum with buffers, salts, and bovine serum albumin. Standards referenced: NCCLS EP5-A, EP6-A, EP7-A, EP9-A2, C28. Automated on VITROS 5,1 FS Chemistry System.

Indications for Use

Indicated for quantitative measurement of ApoA1 and ApoB in human serum and plasma to assist in diagnosis and treatment of lipid disorders (e.g., diabetes mellitus), atherosclerosis, and liver/renal diseases.

Regulatory Classification

Identification

A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)

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.

Predicate Devices

• Dade Behring N Antisera to Human Apolipoprotein A1 and Apolipoprotein B Reagent (k860894)
• N Apolipoprotein Standard Serum (k041870)

Submission Summary (Full Text)

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# Chapter 1 - Summary Information

# 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: 长042521

- Ortho-Clinical Diagnostics, Inc. 1. Submitter 100 Indigo Creek Drive name, Rochester, New York 14626-5101 address, [phone] contact Contact Person: Marlene A. Hanna
- Date 510(k) prepared: September 15, 2004 2. Preparation Date
- Trade or Proprietary Name(s): 3. Device VITROS Chemistry Products ApoA1 Reagent name VITROS Chemistry Products Calibrator Kit 21 VITROS Chemistry Products ApoA1 Performance Verifier I

VITROS Chemistry Products ApoB Reagent VITROS Chemistry Products Calibrator Kit 22 VITROS Chemistry Products ApoB Performance Verifier I

Common Name(s): Apolipoprotein A1 (ApoAl) assay Apolipoprotein B (ApoB) assay

Classification Name(s): Lipoprotein test systems (862.1475): Class: I (general controls). Since these devices (ApoA1 and ApoB reagent) are used in assessing risk of artherosclerosis, they meet the reserved criteria under Section 510(1) of the Food, Drug, and Cosmetic Act.

Calibrator (862.1150): Calibrator Kits 21 and 22: Class II.

Quality Control material (assayed and unassayed) (862.1660): Class I (general controls). Since these devices (ApoA1 and ApoB Performance Verifiers I) are assayed controls, they meet the reserved criteria under Section 510(1) of the Food, Drug, and Cosmetic Act.

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- The VITROS Chemistry Products ApoA1 assay is substantially equivalent to 4. Predicate a. the Dade Behring N Antisera to Human Apolipoprotein A-1 Reagent and N Devices Apoliprotein Standard Serum.
- b. The VITROS Chemistry Products ApoB assay is substantially equivalent to the Dade Behring N Antisera to Human Apolipoprotein B Reagent and N Apoliprotein Standard Serum.
- The VITROS Chemistry Products ApoA1 and ApoB Performance Verifiers I ﻦ are substantially equivalent to the Dade Behring Apolipoprotein Control Serum CHD.
- 5. Device The VITROS 5,1 FS Chemistry System is a fully automated clinical chemistry analyzer intended for use in the in vitro determination of various analytes in human description specimens (serum, plasma, urine, and cerebrospinal fluid). The VITROS 5,1 FS is designed for use with VITROS Chemistry Products MicroTip and Thin Film assays.

The system is comprised of four main elements:

- 1. The VITROS 5,1 FS Chemistry System instrumentation, which provides automated use of the chemistry reagents. The VITROS 5,1 FS Chemistry System was cleared for market by a separate 510(k) premarket notification (K031924).
- 2. The VITROS Chemistry Products MicroTip range of liquid reagent products (in this case VITROS Chemistry Products ApoA1 Reagent and VITROS Chemistry Products Calibrator Kit 21, VITROS Chemistry Products ApoB Reagent and VITROS Chemistry Products Calibrator Kit 22, VITROS Chemistry Products ApoA1 Performance Verifier I and VITROS Chemistry Products ApoB Performance Verifier I ), which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS ApoA1 and ApoB assays.
- 3. The VITROS Chemistry Products Thin Film range of dry products, which are dry, multilayered, analytical elements, coated on polyester supports. The thin film products each have their own 510(k) clearance numbers and were cleared for market for use on the VITROS 5,1 FS Chemistry System through submission of information required by the ODE Guidance Document: "Data For Commercialization Of Original Equipment Manufacturer, Secondary and Generic Reagents For Automated Analyzers". The required information was provided in the VITROS 5,1 FS Chemistry System premarket notification (K031924).
- 4. Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 1).

The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

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- a. VITROS Chemistry Products ApoA1 Reagent: For in vitro diagnostic use only. 6. Device(s) VITROS Chemistry Products ApoA1 Reagent is used to quantitatively measure intended apolipoprotein A1 (ApoA1) concentration in human serum and plasma. use
b. VITROS Chemistry Products ApoB Reagent: For in vitro diagnostic use only. VITROS Chemistry Products ApoB Reagent is used to quantitatively measure apolipoprotein B (ApoB) concentration in human serum and plasma.

c. VITROS Chemistry Products Calibrator Kit 21: For in vitro diagnostic use only, VITROS Chemistry Products Calibrator Kit 21 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of apolipoprotein A1 (ApoA1).

d. VITROS Chemistry Products Calibrator Kit 22: For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 22 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of apolipoprotein B (ApoB).

e. VITROS Chemistry Products ApoA1 Performance Verifier I: For in vitro diagnostic use only. VITROS Chemistry Products ApoA1 Performance Verifier I is an assayed control used to monitor the performance of ApoA1 Reagent on VITROS 5,1 FS Chemistry Systems.

f. VITROS Chemistry Products ApoB Performance Verifier I: For in vitro diagnostic use only. VITROS Chemistry Products ApoB Performance Verifier I is an assaved control used to monitor the performance of ApoB Reagent on VITROS 5,1 FS Chemistry Systems.

### 7. Comparison to predicate

device(s): Apo A1 Reagent Pack and Calibrators

> The VITROS Chemistry Products ApoA1 Reagent and VITROS Chemistry Products Calibrator Kit 21 are substantially equivalent to the Dade Behring N Antisera to Human Apolipoprotein A-1 Reagent (K860894) and N Apoliprotein Standard Serum (K041870) (predicate devices) which were cleared by the FDA for IVD use.

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The relationship between the VITROS ApoA1 and the predicate device, determined by least squares linear regression, is:

VITROS ApoA1 = 0.98 X - 13.04 (mg/dL),

with a correlation coefficient of 0.987,

where X is Dade Behring N Antisera to Human Apolipoprotein A-1 Reagent assay.

### Apo B Reagent Pack and Calibrators

The VITROS Chemistry Products ApoB Reagent and VITROS Chemistry Products Calibrator Kit 22 are substantially equivalent to the Dade Behring N Antisera to Human Apolipoprotein B Reagent (K860894) and N Apoliprotein Standard Serum (K041870) (predicate devices) which were cleared by the FDA for IVD use.

The relationship between the VITROS ApoB and the predicate device, determined by least squares linear regression, is:

VITROS ApoB = 1.00 X - 3.88 (mg/dL),

with a correlation coefficient of 0.985, where X is Dade Behring N Antisera to Human Apolipoprotein B Reagent assay.

In addition to the above mentioned correlation study, studies were performed to determine the precision, specificity, linearity, antigen excess, lower limit of detection, and expected values of the VITROS ApoA1 and ApoB assays, (refer to the VITROS ApoA1 and ApoB Reagent's Instructions for Use for summaries of the results of these studies).

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Table 1 lists the characteristics of the assays performed using the VITROS ApoA1 andApoB assays and the Dade Behring N Antisera to Human Apolipoprotein A-1 Reagent and the Dade Behring N Antisera to Human Apolipoprotein B Reagent assays.

- Table 1 lists the characteristics of the VITROS ApoA1 and ApoB (new devices) Table 1 and the DADE Apo A-1 and Apo B (predicate device).

| Device<br>Characteristic | VITROS ApoA1 and ApoB<br>(New device) | DADE Apo A-1 and ApoB<br>(Predicate device) |
|-----------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For in vitro diagnostic use<br>only. VITROS Chemistry<br>Products ApoA1 and ApoB<br>Reagents are used to<br>quantitatively measure<br>apolipoprotein A1 (ApoA1)<br>and apolipoprotein B (ApoB)<br>concentration in human serum<br>and plasma. | In vitro diagnostic reagents for<br>the quantitative determination<br>of apolipoprotein A-1 (Apo A-<br>1) and apolipoprotein B (Apo<br>B) in human serum. |
| Method | Immunoturbidimetric | Immunoturbidimetric |
| Reportable Range:<br>ApoA1:<br>ApoB: | 30.00-240.00 mg/dL<br>35.00-300.00 mg/dL | 19-600 mg/dL<br>25-400 mg/dL |
| Sample Type | Human Serum | Human Serum |
| Reactive Ingredients<br>ApoA1:<br>ApoB: | Goat antisera to human<br>apolipoprotein A1<br>Goat antisera to human<br>apolipoprotein B | Rabbit antisera to Human<br>ApoA-1<br>Rabbit antisera to Human<br>ApoB |
| Instrumentation | VITROS 5,1 FS Chemistry<br>System | DADE BN ProSpec |

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### Performance Verifiers

The VITROS Chemistry Products ApoA1 and ApoB Performance Verifiers I are substantially equivalent to the Dade Behring Apolipoprotein Control Serum CHD (predicate device) which was cleared by the FDA (K993310) for IVD use.

Table 2 lists the similarities and differences of the device characteristics between the VITROS ApoA1 and ApoB Performance Verifiers I with the predicate device, the Dade Behring Apolipoprotein Control Serum CHD.

Table 2

| Device<br>Characteristic | VITROS ApoA1 and ApoB<br>(New Device) | DADE ApoA1 and ApoB<br>(Predicate Device) |
|--------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For in vitro diagnostic use<br>only. VITROS Chemistry<br>Products ApoA1 and ApoB<br>Performance Verifiers I are<br>assayed controls used to<br>monitor the performance of<br>ApoA1 and ApoB Reagent on<br>VITROS 5,1 FS Chemistry<br>Systems. | Apolipoprotein Control<br>Serum CHD is used as an<br>assayed control for<br>accuracy and precision in<br>the quantitative<br>immunochemical<br>determination of<br>apolipoprotein A-1 and B<br>with the Behring<br>Nephelometer Systems. |
| Matrix | Prepared from processed<br>human serum to which<br>inorganic salts, buffers,<br>organic compounds, bovine<br>serum albumin, and<br>preservatives have been<br>added. | Stabilized reagent from<br>human serum. |
| Form | Liquid | Lyophilized |
| Volume | 0.5 mL per vial | 0.5 mL per vial |

Conclusions The data presented in the premarket notification provide a reasonable assurance that the VITROS ApoAl and ApoB assays and the VITROS Chemistry Products ApoA1 and ApoB Performance Verifiers are safe and effective for the stated intended uses and are substantially equivalent to the cleared predicate devices.

> Equivalence to predicate(s) was demonstrated using commercially available reagents along with patient samples.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/12 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the symbol. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Marlene A Hanna, RAC Regulatory Affairs Associate Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101

NOV 1 8 2004

Re: k042521

> Trade/Device Name: VITROS Chemistry Products ApoA1 Reagent VITROS Chemistry Products Calibrator Kit 21 VITROS Chemistry Products ApoA1 Performance Verifier I VITROS Chemistry Products ApoB Reagent VITROS Chemistry Products Calibrator Kit 22 VITROS Chemistry Products ApoB Performance Verifier I Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIT, MSJ, JJX Dated: September 15, 2004 Received: September 16, 2004

Dear Ms. Hanna:

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 http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sincerely yours,

Cornelia B. Parks

Cornelia B. Rooks, MA Acting 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 for the ApoA1 assay

510(k) Number (if known):

VITROS Chemistry Products ApoA1 Reagent Device Name(s): VITROS Chemistry Products Calibrator Kit 21 VITROS Chemistry Products ApoA1 Performance Verifier I Indications for Use: For in vitro diagnostic use only. VITROS Chemistry Products ApoA1 Reagent is used to quantitatively measure apolipoprotein A1 (ApoA1) concentration in human serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 21 is used to calibrate VITROS 5.1 FS Chemistry Systems for the quantitative measurement of apolipoprotein A 1 (ApoA1). For in vitro diagnostic use only. VITROS Chemistry Products ApoA1 Performance Verifier I is an assayed controls used to monitor the performance of ApoA1 Reagent on VITROS 5,1 FS Chemistry Systems. ﺳﺎ

Prescription Use _ (Per 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use _ (Per 21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Page 1 of

Carol Benn
Division Sign-Off

Office of in Vitro Diagnostic Devina Evaluation and Safety

510(k) K042521

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# Indications for Use for the ApoB assay

510(k) Number (if known):

| Device Name(s): | VITROS Chemistry Products ApoB Reagent |
|----------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | VITROS Chemistry Products Calibrator Kit 22 |
| | VITROS Chemistry Products ApoB Performance Verifier I |
| Indications for Use: | For in vitro diagnostic use only. VITROS Chemistry Products ApoB Reagent is used to quantitatively measure apolipoprotein B (ApoB) concentration in human serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. |
| | For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 22 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of apolipoprotein B (ApoB). |
| | For in vitro diagnostic use only. VITROS Chemistry Products ApoB Performance Verifier I is an assayed controls used to monitor the performance of ApoB Reagent on VITROS 5,1 FS Chemistry Systems. |

Prescription Use
(Per 21 CFR 801 Subpart D)

AND/OR

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Over-The-Counter Use _ (Per 21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Page 2 of 2 - 1

Carol Benner
Division Sign Off

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

EiO(k) K04252