VITROS CHEMISTRY PRODUCTS DLDL REAGENT, CALIBRATOR KIT 19, FS CALIBRATOR 1 AND PERFORMANCE VERIFIERS I AND II

K041720 · Ortho-Clinical Diagnostics, Inc. · MRR · Aug 25, 2004 · Clinical Chemistry

Device Facts

• Record ID: K041720
• Device Name: VITROS CHEMISTRY PRODUCTS DLDL REAGENT, CALIBRATOR KIT 19, FS CALIBRATOR 1 AND PERFORMANCE VERIFIERS I AND II
• Applicant: Ortho-Clinical Diagnostics, Inc.
• Product Code: MRR · Clinical Chemistry
• Decision Date: Aug 25, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1475
• Device Class: Class 1

Intended Use

For in vitro diagnostic use only. VITROS Chemistry Products dLDL Reagent is used to quantitatively measure LDL Cholesterol (LDLC) concentration in serum and plasma. Low Density Lipoprotein (LDL) cholesterol is used to evaluate the risk of developing coronary heart disease (CHD). The risk of CHD increases with higher LDL cholesterol concentrations. For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 19 is used in conjunction with VITROS FS Calibrator 1 to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of HDL and LDL cholesterol using VITROS dHDL and dLDL Reagents. For in vitro diagnostic use only. VITROS Chemistry Products Performance Verifiers I and II are assayed controls used to monitor performance on VITROS Chemistry Systems.

Device Story

VITROS dLDL Reagent is a dual-chambered, ready-to-use liquid reagent system for quantitative measurement of LDL cholesterol. Used on VITROS 5,1 FS Chemistry Systems in clinical laboratory settings. Operation involves a two-step enzymatic reaction: step one selectively eliminates non-LDL cholesterol (HDL, VLDL, chylomicrons) using cholesterol esterase/oxidase and catalase; step two inactivates catalase with sodium azide, then dissociates LDL cholesterol using surfactants for enzymatic reaction with TOOS and 4-aminoantipyrine. Resulting quinone dye is measured spectrophotometrically at 600 nm. Output is a quantitative LDL concentration value used by clinicians to assess CHD risk based on NCEP ATP III guidelines. System includes calibrators and assayed controls to ensure performance accuracy.

Clinical Evidence

Bench testing only. Performance evaluated via precision (ANOVA, CV% 2.22-3.50%), linearity (21-402 mg/dL), and method comparison (n=165, slope 1.03, r=0.991). Interference studies confirmed no significant bias for triglycerides up to ~750 mg/dL or common endogenous/exogenous substances. No clinical prospective/retrospective studies performed.

Technological Characteristics

Elimination enzymatic assay; liquid ready-to-use reagents. Instrumentation: VITROS 5,1 FS Chemistry System. Reaction steps: elimination followed by measurement at 37°C. Sample types: serum and plasma (heparin). Performance Verifiers: freeze-dried human serum matrix with added enzymes, electrolytes, stabilizers, and preservatives.

Indications for Use

Indicated for quantitative measurement of LDL cholesterol in serum and plasma to evaluate coronary heart disease (CHD) risk in patients. No specific age or gender restrictions noted.

Regulatory Classification

Identification

A lipoprotein test system is a device intended to measure lipoprotein in 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.

Predicate Devices

• Polymedco Lipi+Plus Direct LDL assay (K020852)
• VITROS Chemistry Products Performance Verifiers (K904768)

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: KOY 1720

- Ortho-Clinical Diagnostics, Inc. Submitter 1. name, 100 Indigo Creek Drive address, Rochester, New York 14626-5101 [phone] contact
Contact Person: Marlene A. Hanna

- Date 510(k) prepared: June 23, 2004 2. Preparation date
- Trade or Proprietary Name: 3. Device VITROS Chemistry Products dLDL Reagent name VITROS Chemistry Products Calibrator Kit 19 VITROS Chemistry Products FS Calibrator 1 VITROS Chemistry Products Performance Verifiers I and II

Common Name: Direct LDL assay

Classification Name: Lipoprotein test system (862.1475): Class: I: The Clinical Chemistry and Toxicology Panel of the FDA has placed lipoprotein test systems in Class I. Since this device is an in vitro device intended for use in assessing the risk of cardiovascular diseases, it meets the reserved criteria under Section 510(1) of the Food, Drug, and Cosmetic Act.

Classification Name: Quality Control material (assayed and unassayed) (862.1660): Class I: The Clinical Chemistry and Toxicology Panel of the FDA has placed Quality Control material (assayed and unassayed) for clinical chemistry in Class I. Since this device is an assayed control, it meets the reserved criteria under Section 510(1) of the Food, Drug, and Cosmetic Act.

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# 510(k) Summary, Continued

- a. The VITROS Chemistry Products dLDL assay is substantially equivalent to the 4. Predicate Polymedco Lipi+Plus Direct LDL assay. Device
b. The VITROS Chemistry Products Performance Verifiers I and II are substantially equivalent to the VITROS Chemistry Products Performance Verifiers I and II.

- The VITROS 5.1 FS Chemistry System is a fully automated clinical chemistry 5. Device 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 dLDL Reagent, VITROS Chemistry Products Calibrator Kit 19 and VITROS Chemistry Products FS Calibrator 1, VITROS Chemistry Products Performance Verifiers I and II), which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS dLDL assay.
- 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 there 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 2 and VITROS Chemistry Products FS Reconstitution Diluent).

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 dLDL Reagent: For in vitro diagnostic use only. 6. Device intended The VITROS Chemistry Products dLDL Reagent is used to quantitatively measure LDL Cholesterol (LDLC) concentration in serum and plasma. Low Density use Lipoprotein (LDL) cholesterol is used to evaluate the risk of developing coronary heart disease (CHD). The risk of CHD increases with higher LDL cholesterol concentration.

> b. VITROS Chemistry Products Calibrator Kit 19 and VITROS Chemistry Products FS Calibrator 1: For in vitro diagnostic use only. The VITROS Chemistry Products Calibrator Kit 19 is used in conjunction with VITROS FS Calibrator 1 to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of HDL and LDL cholesterol using VITROS dHDL and dLDL Reagents.

c. VITROS Chemistry Products Performance Verifiers I and II: For in vitro diagnostic use only. The VITROS Chemistry Products Performance Verifiers I and II are assayed controls used to monitor performance on VITROS Chemistry Systems.

# 7. Comparison to predicate device(s):

#### Reagent Pack and Calibrators

The VITROS Chemistry Products dLDL Reagent and VITROS Chemistry Products Calibrator Kit 19 and FS Calibrator 1 are substantially equivalent to the Polymedco Lipi+Plus Direct LDL assay (predicate device) which was cleared by the FDA (K020852) for IVD use.

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

VITROS dLDL = 1.031 x X - 3.81 (mg/dL), with a correlation coefficient of 0.9908, where X is the Polymedco Lipi+Plus Direct LDL assay on a Dade Dimension clinical chemistry analyzer.

In addition to the above mentioned correlation study, studies were performed to determine the precision, specificity, linearity, and expected values of the VITROS dLDL assay, (refer to the VITROS dLDL Reagent Instructions for Use for summaries of the results of these studies).

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# 510(k) Summary, Continued

Table 1 lists the characteristics of the assays performed using the VITROS dLDL assay and the Polymedco Lipi+Plus Direct LDL assay.

| Device<br>Characteristic | VITROS dLDL<br>(New device) | dLDL<br>(Predicate device) |
|---------------------------|--------------------------------------------|---------------------------------------------|
| Reportable Range | 30 - 350 mg/ dL | 0 - 1000 mg/dL |
| Specimen Pretreatment | None Required:<br>Homogeneous assay | None Required:<br>Homogeneous assay |
| Basic Principle | Elimination enzymatic test | Elimination enzymatic test |
| Reagents | Liquid ready to use | Liquid ready to use |
| Instrumentation | VITROS 5,1 FS Chemistry<br>System | Dade Dimension clinical<br>chemistry system |
| Sample Type | Serum and Plasma (heparin) | Serum and Plasma (heparin<br>and EDTA) |
| Reaction steps | Step 1: Elimination<br>Step 2: Measurement | Step 1: Elimination<br>Step 2: Measurement |
| Incubation<br>Temperature | 37 °C | 37 °C |

#### Table 1 lists the characteristics of the VITROS dLDL (new device) and the dLDL Table 1

## Performance Verifiers

The VITROS Chemistry Products Performance Verifiers I and II are substantially equivalent to the VITROS Chemistry Products Performance Verifiers (predicate device) which were cleared by the FDA (K904768) for IVD use.

#### Table 2

Table 2 lists the similarities and differences of the device characteristics between the VITROS Performance Verifiers with the predicate device, VITROS Performance Verifiers I and II.

| Device<br>Characteristic | VITROS dLDL (New device) | dLDL (Predicate device) |
|---------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | VITROS Performance Verifier is an assayed control used to monitor performance on VITROS Chemistry Systems. (New additional intended use: to monitor performance of LDL Cholesterol on the VITROS 5,1 FS Chemistry System.) | VITROS Performance Verifier is an assayed control used to monitor performance on VITROS Chemistry Systems. |
| Matrix of<br>Performance<br>Verifiers | A base matrix of freeze-dried human serum to which enzymes, electrolytes, stabilizers, preservatives and other organic analytes have been added. | A base matrix of freeze-dried human serum to which enzymes, electrolytes, stabilizers, preservatives and other organic analytes have been added. |
| Performance<br>Verifier Levels | Low and High | Low and High |

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# 510(k) Summary, Continued

The data presented in the premarket notification provide a reasonable assurance Conclusions that the VITROS dLDL assay and the VITROS Chemistry Products Performance Verifiers are safe and effective for the stated intended uses and are substantially equivalent to the cleared predicate devices. The data in this premarket notification demonstrate that the performance of the VITROS dLDL assay and Performance Verifiers are substantially equivalent to the cleared predicate device(s).

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

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Image /page/5/Picture/1 description: The image shows a logo for the Department of Health & Human Services. The logo consists of a symbol resembling a stylized human figure with three wavy lines extending from its head, all enclosed within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged around the perimeter of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

AUG 2 5 2004

k041720 Re:

Trade/Device Name: VIRTOS Chemistry Products dLDL Reagent VIRTOS Chemistry Products Calibrator Kit 19 VIRTOS Chemistry Products FS Calibrator 1 VIRTOS Chemistry Products Performance Verifiers I and II Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIT, JJX, MRR, Dated: June 23, 2004 Received: June 24, 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.

Jean M. Corgan, MS, DVM.

Jean M. Cooper, MS, D.V.M. 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): | K041720 |
| Device Name(s): | VITROS Chemistry Products dLDL Reagent<br>VITROS Chemistry Products Calibrator Kit 19<br>VITROS Chemistry Products FS Calibrator 1<br>VITROS Chemistry Products Performance Verifiers I and II |
| Indications for Use: | For <i>in vitro</i> diagnostic use only. VITROS Chemistry Products dLDL Reagent is used to quantitatively measure LDL Cholesterol (LDLC) concentration in serum and plasma. Low Density Lipoprotein (LDL) cholesterol is used to evaluate the risk of developing coronary heart disease (CHD). The risk of CHD increases with higher LDL cholesterol concentrations.<br><br>For <i>in vitro</i> diagnostic use only. VITROS Chemistry Products Calibrator Kit 19 is used in conjunction with VITROS FS Calibrator 1 to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of HDL and LDL cholesterol using VITROS dHDL and dLDL Reagents.<br><br>For <i>in vitro</i> diagnostic use only. VITROS Chemistry Products Performance Verifiers I and II are assayed controls used to monitor performance on VITROS Chemistry Systems. |
| Prescription Use<br>(Per 21 CFR 801 Subpart D) | AND/OR                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         &p> |

Concurrence of CDRH, Office of Device Evaluation (ODE)

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Caul Benson
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K041720

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