VITROS CHEMISTRY PRODUCTS C3 AND CR REAGENT, CALIBRATOR KIT 20, PROTEIN PERFORMANCE VERIFIERS I, II, AND III

K042494 · Ortho-Clinical Diagnostics · CZW · Oct 19, 2004 · Immunology

Device Facts

• Record ID: K042494
• Device Name: VITROS CHEMISTRY PRODUCTS C3 AND CR REAGENT, CALIBRATOR KIT 20, PROTEIN PERFORMANCE VERIFIERS I, II, AND III
• Applicant: Ortho-Clinical Diagnostics
• Product Code: CZW · Immunology
• Decision Date: Oct 19, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5240
• Device Class: Class 2

Intended Use

VITROS Chemistry Products C3 and C4 reagents are used to quantitatively measure C3 and C4 concentration in human serum and plasma. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components. VITROS Calibrator kit 20 is used to calibrate VITROS 5,1 FS Chemistry System for quantitative measurement of transferrin, C3, C4, IgA and IgM (multianalytes). VITROS Chemistry Products Protein Performance Verifiers I, II and III are assayed controls used to monitor the performance of Transferrin, C3, C4, IgA and IgM Reagents on the FS 5,1 Chemistry Systems.

Device Story

VITROS Chemistry Products C3 and C4 reagents are liquid-based assays for use on the VITROS 5,1 FS Chemistry System. The system, operated by laboratory personnel, automates the processing of human serum or plasma samples. The device utilizes immunoturbidimetry to measure C3 and C4 concentrations. The system also employs a dedicated Calibrator Kit 20 and Protein Performance Verifiers to ensure analytical accuracy and monitor performance. Output is a quantitative concentration value provided to the clinician, which assists in diagnosing immunologic disorders. The device benefits patients by providing rapid, automated diagnostic information regarding complement system status.

Clinical Evidence

Bench testing only. Performance validated via correlation studies comparing VITROS C3/C4 assays to predicate devices using patient samples. Results demonstrated strong linear correlation (C3: r=0.98, slope=0.95; C4: r=0.976, slope=0.93). Precision, analytical sensitivity, and specificity were evaluated to confirm performance equivalence.

Technological Characteristics

Thin-film, dry-reagent chemistry on polyester supports. Immunoturbidimetric sensing principle. Requires VITROS 5,1 FS Chemistry System. Calibrators and controls prepared from processed human serum with buffers, salts, and preservatives. Traceable to IRMM/IFCC CRM 470. Complies with NCCLS guidelines EP5-A, EP-7A, EP-9A, C28.

Indications for Use

Indicated for use as an aid in the diagnosis of immunologic disorders associated with complement component deficiencies in human serum and plasma. Prescription use only.

Regulatory Classification

Identification

A complement components immunological test system is a device that consists of the reagents used to measure by immunochemical techniques complement components C1q , C1r , C1s , C2 , C3 , C4 , C5 , C6 , C7 , C8 , and C9 , in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.

Predicate Devices

• IMMAGE Immunochemistry System Complement C3 Reagent (K964842)
• Dade Behring N Antisera to Human Complement C4 (K860894)
• VITROS Chemistry Products Performance Verifiers I and II (K041720)

Submission Summary (Full Text)

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## DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular emblem with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the top half of the circle. Inside the circle is a stylized image of an eagle with its wings outstretched. The eagle is depicted in a simple, abstract style, with only a few lines used to create its form.

### Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

# NOV 8 - 2004

Ms. Darlene Phillips Regulatory Affairs Associate Ortho-Clinical Diagnostics 100 Indigo Creek Drive Rochester, New York 14626-5101

Re: k042494

Trade/Device Name: VITROS Chemistry Products C3 Reagent VITROS Chemistry Products C4 Reagent VITROS Chemistry Products Calibrator Kit 20 VITROS Chemistry Products Protein Performance Verifiers I, II and III

Regulation Number: 21 CFR 866.5240 Regulation Name: Complement Components Immunological Test System Regulatory Class: Class II Product Code: CZW, DBI, JIT, JJY Dated: September 13, 2004 Received: September 14, 2004

Dear Ms Phillips:

This letter corrects our substantially equivalent letter of October 19, 2004 regarding the VITROS Chemistry Products C3 Reagent, VITROS Chemistry Products C4 Reagent, VITROS Chemistry Products Calibrator Kit 20 and VITROS Chemistry Products Protein Performance Verifiers I, II and III in which the VITROS Chemistry Products C4 Reagent was omitted from the listing of the trade name(s).

We have reviewed your Section 510(k) premarket notification of intent to market the devices referenced above and have determined the devices are 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 (PMA). You may, therefore, market the devices, 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.

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## Page 2

If your devices are classified (see above) into either class II (Special Controls) or class III (PMA), they may be subject to additional controls. Existing major regulations affecting your devices can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your devices 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 devices comply 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (sections 531-542 of the Act); 21 CFR 1000-1050.

This letter will allow you to continue marketing your devices as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your devices to legally marketed predicate devices results in a classification for your devices and thus, permits your devices to proceed to the market.

If you desire specific advice for your devices on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance 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 vours.

Robert Beckerh

Robert L. Becker, Jr., M.D., PhD DIRECTOR Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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### 1.0 Indications for Use for VITROS C3 assay

| 510(k) Number (if known): | K042494 |
|-----------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name: | VITROS Chemistry Products C3 Reagent<br>VITROS Chemistry Products Calibrator Kit 20<br>VITROS Chemistry Products Protein Performance Verifiers I, II and III |
| Indications for Use: | For <i>in vitro</i> diagnostic use only. VITROS Chemistry Products C3 Reagent is used to quantitatively measure complement C3 (C3) concentration in human serum and plasma. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.<br><br>For <i>in vitro</i> diagnostic use. VITROS Chemistry Products Calibrator Kit 20 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of transferrin, C3, C4, IgA, IgG and IgM.<br><br>For <i>in vitro</i> diagnostic use only. VITROS Chemistry Products Protein Performance Verifiers are assayed controls used to monitor the performance of TRFRN, C3, C4, IgA, IgG and IgM Reagents on VITROS 5,1 FS Chemistry Systems. |
| Prescription Use | <div style="display:inline-block; width:20px; height:20px; border:1px solid black;"> <span style="position:relative; top:-2px; left:2px;">X</span> </div> |
| (Part 21 CFR 801 Subpart D) | |
| | AND/OR |
| Over-The-Counter Use | |
| (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)

Mara In Chan

---

**Division Sign-Off**

Office of In Vitro Diagn

Office of In Vitro Diagnostic
Device Evaluation and Safety

510(k) K042494

Page 1 of 2

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### Indications for Use for VITROS C4 assay 2.0

| 510(k) Number (if known): | KO42494 |
|-------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name: | VITROS Chemistry Products C4 Reagent<br>VITROS Chemistry Products Calibrator Kit 20<br>VITROS Chemistry Products Protein Performance Verifiers I, II and III |
| Indications for Use: | For <i>in vitro</i> diagnostic use only. VITROS Chemistry Products C4 Reagent is used to quantitatively measure complement C4 (C4) concentration in human serum and plasma. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.<br>For <i>in vitro</i> diagnostic use. VITROS Chemistry Products Calibrator Kit 20 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of transferrin, C3, C4, IgA, IgG and IgM.<br>For <i>in vitro</i> diagnostic use only. VITROS Chemistry Products Protein Performance Verifiers are assayed controls used to monitor the performance of TRFRN, C3, C4, IgA, IgG and IgM Reagents on VITROS 5,1 FS Chemistry Systems. |
| Prescription Use<br>(Part 21 CFR 801 Subpart D) | <div> <span> ✓ </span> <span>AND/OR</span> <span>Over-The-Counter Use<br/>(21 CFR 807 Subpart C)</span> </div> |
| (PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF<br>NEEDED) | |

Concurrence of CDRH, Office of Device Evaluation (ODE)

Mana M. Clan

**Division Sign-Off**

Office of in Vitro Diagnosilic Device Evaluation and Safety

510(k) K042494

Page 2 of 2

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# OCT 1 9 2004

## 4.0 510(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: KOYA 494

#### 4.1 Submitter name, address, contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 Phone: [phone] Fax: [phone]

Contact Person: Darlene J. Phillips

#### 4.2 Date of Preparation:

September 13, 2004

#### 4.3 Device Proprietary Names:

VITROS Chemistry Products C3 Reagent Trade Names VITROS Chemistry Products C4 Reagent VITROS Chemistry Products Calibrator Kit 20 VITROS Chemistry Products Protein Performance Verifiers I. II and III

Common Name Complement C3 and C4 assays

#### 4.4 Classification Names

Classification Name: Complement components immunological test systems (866.5240): Class: II (Performance standards)

Classification Name: Calibrator (862.1150): Class II The Clinical Chemistry and Toxicology Panel of the FDA has placed calibrators in Class II.

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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#### 4.5 Predicate device

- 4.5.1 The VITROS Chemistry Products C3 Reagent and VITROS Chemistry Products Calibrator Kit 20 are substantially equivalent to the IMMAGE® Immunochemistry System Complement C3 Reagent assayed on the Beckman IMMAGE® Immunochemistry System.
- The VITROS Chemistry Products C4 Reagent and VITROS Chemistry Products 4.5.2 Calibrator Kit 20 are substantially equivalent to the Dade Behring N Antisera to Human Complement C4 assayed on the Dade Behring BN® ProSpec Nephelometer.
- 4.5.3 The VITROS Chemistry Products Protein Performance Verifiers 1, II and III are substantially equivalent to the VITROS Chemistry Products Performance Verifiers I and II.

#### 4.6 Device description

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 specimens (serum, plasma, urine, and cerebrospinal fluid). The VITROS 5,1 FS System is designed for use with VITROS Chemistry Products MicroTip and Thin Film assays.

The system is comprised of four main elements:

- l . 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 liguid reagent products (in this case VITROS Chemistry Products C3 Reagent, VITROS Chemistry Products C4 Reagent, VITROS Chemistry Products Calibrator Kit 20 and VITROS Chemistry Products Protein Performance Verifiers I, II and III), which are combined on the VITROS 5,1 FS Chemistry System to perform the VITROS C3 and C4 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, I FS Chemistry System premarket notification (K031924).

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- 4. Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 2).
The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

#### 4.7 Device intended use

#### 4.7.1 VITROS Chemistry Products C3 Reagent

For in vitro diagnostic use only. VITROS Chemistry Products C3 Reagent is used to quantitatively measure complement C3 (C3) concentration in human serum and plasma. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.

#### 4.7.2 VITROS Chemistry Products C4 Reagent

For in vitro diagnostic use only. VITROS Chemistry Products C4 Reagent is used to quantitatively measure complement C4 (C4) concentration in human serum and plasma. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.

#### 4.7.3 VITROS Chemistry Products Calibrator Kit 20

For in vitro diagnostic use. VITROS Chemistry Products Calibrator Kit 20 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of transferrin, C3, C4, IgA, IgG and IgM.

#### 4.7.4 VITROS Chemistry Products Protein Performance Verifiers I, II and III

For in vitro diagnostic use only. VITROS Chemistry Products Protein Performance Verifiers are assayed controls used to monitor the performance of TRFRN. C3. C4. IgA, IgG and IgM Reagents on VITROS 5,1 FS Chemistry Systems.

#### 4.8 Comparison to predicate device

- 4.8.1 The VITROS Chemistry Products C3 Reagent and VITROS Chemistry Products Calibrator Kit 20 are substantially equivalent to the IMMAGE® Immunochemistry System Complement C3 Reagent assayed on the Beckman IMMAGE® Immunochemistry System (predicate device #1) which was cleared by the FDA (K964842) for IVD use.
Continued on next page

The relationship between the VITROS C3 assay and the predicate device, determined by the least squares linear regression is:

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VITROS C3 assav = 0.95x X + 11 mg/dL.

with a correlation coefficient of 0.98.

where X is the IMMAGE® Immunochemistry System Complement C3 Reagent assayed on the Beckman IMMAGE® Immunochemistry System.

In addition to the above mentioned correlation studies were performed to determine the precision, analytical sensitivity, specificity and expected values of the VITROS C3 assay, (refer to VITROS C3 Reagent Instructions For Use for summaries of the results of these studies).

- The VITROS Chemistry Products C4 Reagent and VITROS Chemistry Products 4.8.2 Calibrator Kit 20 are substantially equivalent to the Dade Behring N Antisera to Human Complement C4 assayed on the Dade Behring BN® ProSpec Nephelometer (predicate device #2) which was cleared by the FDA (K860894) for IVD use,
The relationship between the VITROS C4 assay and the predicate device. determined by the least squares linear regression is:

VITROS C4 assay = 0.93x X + 3.0 mg/dL.

with a correlation coefficient of 0.976,

where X is the Dade Behring N Antisera to Human Complement C4 assayed on the Dade Behring BN® ProSpec Nephelometer.

In addition to the above mentioned correlation study, studies were performed to determine the precision, analytical sensitivity, specificity and expected values of the VITROS C4 assay, (refer to VITROS C4 Reagent Instructions For Use for summaries of the results of these studies).

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| Device<br>Characteristic | VITROS C3 assay<br>(New Device #1) | Beckman C3 assay<br>(Predicate Device #1) |
|--------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For in vitro diagnostic use only.<br>VITROS Chemistry Products C3<br>Reagent is used to quantitatively<br>measure complement C3 (C3)<br>concentration in human serum.<br>Measurements of these proteins aids in<br>the diagnosis of immunologic disorders.<br>especially those associated with<br>deficiencies of complement components. | C3 Reagent, when used in<br>conjunction with IMMAGE<br>Immunochemistry Systems and<br>Calibrator 1, is intended for the<br>quantitative determination of<br>Complement C3 (C3) in human<br>serum by rate nephelometry. |
| Method | Immunoturbidimetry | Rate nephelometry |
| Reportable Range | 40 - 380 mg/dL | 35- 350 mg/dL |
| Instrumentation | VITROS 5,1 FS Chemistry Systems | IMMAGE Immunochemistry<br>Systems |
| Sample type | Serum and plasma | Serum |
| Reactive Ingredient | Goat anti-sera to human C3 | C3 Antibody (processed goat sera) |

Table 1 lists the characteristics of the VITROS C3 assay (new device #1) and the Beckman Table 1 C3 assay (predicate device #1).

Table 2 Table 2 lists the characteristics of the VITROS C4 assay (new device #2) and the Dade Behring C4 assay (predicate device #2).

| Device<br>Characteristic | VITROS C4 assay<br>(New Device #2) | Dade Behring C4 assay<br>(Predicate Device #2) |
|--------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For in vitro diagnostic use only.<br>VITROS Chemistry Products C4<br>Reagent is used to quantitatively<br>measure complement C4 (C4)<br>concentration in human serum.<br>Measurements of these proteins aids<br>in the diagnosis of immunologic<br>disorders, especially those associated<br>with deficiencies of complement<br>components. | In vitro diagnostic reagents for the<br>quantitative determination of<br>complement factor (C4) in human<br>serum using the BN Systems. |
| Method | Immunoturbidimetry | Rate nephelometry |
| Reportable Range | 8.0 - 60.0 mg/dL | 6 - 190 mg/dL |
| Instrumentation | VITROS 5,1 FS Chemistry Systems | Dade Behring Nephlometer |
| Sample type | Serum and plasma | Serum |
| Reactive Ingredient | Goat anti-sera to human C4 | Antiserum to human C4 |

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- The VITROS Chemistry Products Protein Performance Verifiers I, II and III are 4.8.3 substantially equivalent to the VITROS Chemistry Products Performance Verifiers (predicate device) which were cleared by the FDA (K041720) for IVD use.
Table 3 lists the similarities and differences of the device characteristics between the Table 3 VITROS Protein Performance Verifiers with the predicate device, VITROS Performance Verifiers I and II.

| Device<br>Characteristic | New device | Predicate device |
|--------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For in vitro diagnostic use only.<br>VITROS Chemistry Products Protein<br>Performance Verifiers are assayed<br>controls used to monitor the<br>performance of TRFRN, C3, C4,<br>IgA, IgG and IgM Reagents on<br>VITROS 5,1 FS Chemistry Systems. | For in vitro diagnostic use only.<br>VITROS Performance Verifiers<br>are assayed controls used to<br>monitor performance on VITROS<br>Chemistry Systems. |
| Fluid Matrix | A base matrix of human serum to<br>which inorganic salts, buffers and<br>preservatives have been added. | A base matrix of freeze-dried<br>human serum to which enzymes,<br>electrolytes, stabilizers,<br>preservatives and other organic<br>analytes have been added. |
| Analyte Levels | Low, Medium and High | Low and High |
| Analytes Monitored | TRFRN, C3, C4, IgA, IgG and IgM | Multiple analytes including ALB<br>ALT, AMYL, Bc, Bu, BUN, Ca,<br>Cl-, DGXN, ECO2, Fe, GLU,<br>K+, LDH, Li, Mg, Na+, PHOS,<br>TBIL, TP, URIC |

#### 4.9 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS C3 and C4 assays and the VITROS Chemistry Products Protein Performance Verifiers are safe and effective for the stated intended uses and are substantially equivalent to the cleared predicate devices. Equivalence to the predicates was demonstrated using commercially available reagents along with patient samples.