VITROS CHEMISTRY PRODUCTS HCY 2 REAGENT, CALIBRATOR KIT 27, HCY 2 PERFORMANCE VERIFIERS I, II AND III

K123930 · Ortho-Clinical Diagnostics, Inc. · LPS · May 15, 2013 · Clinical Chemistry

Device Facts

• Record ID: K123930
• Device Name: VITROS CHEMISTRY PRODUCTS HCY 2 REAGENT, CALIBRATOR KIT 27, HCY 2 PERFORMANCE VERIFIERS I, II AND III
• Applicant: Ortho-Clinical Diagnostics, Inc.
• Product Code: LPS · Clinical Chemistry
• Decision Date: May 15, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1377
• Device Class: Class 2

Intended Use

VITROS Chemistry Products HCY 2 Reagent: For in vitro diagnostic use only. VITROS Chemistry Products HCY 2 Reagent is used on VITROS Systems to quantitatively measure total homocysteine concentration in human serum and plasma. Serum and plasma homocysteine levels can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia and homocystinuria. VITROS Chemistry Products HCY 2 Performance Verifiers I, II & III: For in vitro diagnostic use only. VITROS Chemistry Products HCY 2 Performance Verifiers are assayed controls used to monitor performance of VITROS Chemistry Products HCY and VITROS Chemistry Products HCY 2 Reagents on VITROS 5,1 FS Chemistry Systems, VITROS 4600 Chemistry Systems and VITROS 5600 Integrated Systems.

Device Story

VITROS® Chemistry Products HCY 2 Reagent is an in vitro diagnostic assay for measuring total homocysteine in human serum and plasma. The device uses a dual-chambered reagent pack containing TCEP to reduce oxidized homocysteine, followed by enzymatic conversion via cystathionine β-synthase (CBS) and cystathionine β-lyase (CBL) to produce ammonia, pyruvate, and homocysteine. Pyruvate is subsequently reduced to lactate by lactate dehydrogenase (LDH) using NADH as a coenzyme. The concentration of homocysteine is determined spectrophotometrically at 340 nm, where NADH consumption is directly proportional to homocysteine levels. The assay is performed on automated VITROS® Chemistry Systems (5.1 FS, 4600, 5600) by laboratory professionals. Results assist clinicians in diagnosing and managing hyperhomocysteinemia and homocystinuria. Performance verifiers (I, II, III) are processed human serum controls used to monitor assay accuracy and precision.

Clinical Evidence

Bench testing only. Precision studies (n ≥ 80 per level) showed within-lab CVs of 1.7-3.5%. Linearity was confirmed across 0.3–74.9 μmol/L, supporting a reportable range of 2–50 μmol/L. Method comparison against the predicate (n ≥ 110) showed high correlation (r ≥ 0.993) and slopes near 1.0. Interference testing identified potential positive bias from cystathionine and L-cysteine. Reference intervals were validated via transference and confirmed with 40 healthy adults.

Technological Characteristics

Quantitative enzymatic assay. Reagents: LDH, Serine, NADH, TCEP, Cystathionine beta-synthase, Cystathionine beta-lyase. Instrumentation: VITROS 5,1 FS, 4600, and 5600 Chemistry Systems. Measurement: Spectrophotometric at 340 nm. Connectivity: Integrated with VITROS chemistry platforms. Storage: 2-8°C.

Indications for Use

Indicated for quantitative measurement of total homocysteine in human serum and plasma to assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia and homocystinuria. Prescription use only.

Regulatory Classification

Identification

A urinary homocystine (nonquantitative) test system is a device intended to identify homocystine (an analogue of the amino acid cystine) in urine. The identification of urinary homocystine is used in the diagnosis and treatment of homocystinuria (homosystine in urine), a heritable metabolic disorder which may cause mental retardation.

Predicate Devices

• VITROS® Chemistry Products HCY Reagent (K061588)
• VITROS® Chemistry Products HCY Performance Verifiers (K061588)

Submission Summary (Full Text)

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#### 5.0 510(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: _ K123930

- Ortho-Clinical Diagnostics, Inc. 1. Submitter 100 Indigo Creek Drive name, address, Rochester, New York 14626-5101. [phone] contact Contact Person: Michael Byrne
- December 19, 2012 2. Preparation Date
- Trade or Proprietary Names: 3. Device name VITROS® Chemistry Products HCY 2 Reagent VITROS® Chemistry Products HCY 2 Performance Verifiers I, II & III

Common Names: HCY assay and controls

#### Classification Names:

Urinary homocystine (nonquantitative) test system (21 CFR 862.1377) Class II

Quality Control material (assayed and unassayed) (21 CFR 862.1660) Class I (reserved). Since these devices (VITROS® HCY 2 Performance Verifiers I, II & III) are assayed controls, they meet the reserved criteria under Section 510(1) of the Food, Drug, and Cosmetic Act.

Product Code: LPS, JJX

Panel: Clinical Chemistry

Continued on next page

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- 4. Predicate The VITROS® Chemistry Products HCY 2 assay is substantially equivalent to the previously cleared VITROS® Chemistry Products HCY Reagent Devices (K061588).
The VITROS® Chemistry Products HCY 2 Performance Verifiers are substantially equivalent to the previously cleared VITROS® Chemistry Products HCY Performance Verifiers (K061588).

- The VITROS® Chemistry Products HCY 2 Reagent is used in conjunction 5. Device description with the VITROS® Chemistry Products Calibrator Kit 27 and VITROS® Chemistry Products FS Diluent Pack 2 (BSA/Saline) on VITROS® 5.1 FS Chemistry Systems, VITROS® 4600 Chemistry Systems, and the VITROS® 5600 Integrated Systems to quantitatively measure total homocysteine concentration in human serum and plasma.
The VITROS® Chemistry Products HCY 2 Reagent consists of one dual chambered reagent pack containing two ready-to-use liquid reagents, one in each chamber. Disulfide linked homocysteine (oxidized forms) in the sample is reduced by Tris (2-Carboxyethyl) Phosphine hydrochloride (TCEP) to form reduced homocysteine. Reduced homocysteine reacts with serine in the presence of cystathionine ß-synthase (CBS) to form Lcystathionine. L-cystathionine is broken down by cystathionine ß-lyase (CBL) to produce homocysteine, pyruvate and ammonia. Pyruvate is reduced to lactate by lactate dehydrogenase (LDH) using NADH as coenzyme. The concentration of homocysteine is directly proportional to the amount of NADH converted to NAD and is measured spectrophotometrically at 340 nm.

The VITROS® Chemistry Products Calibrator Kit 27 is prepared from an aqueous solution containing amino acids and inorganic acid. These standards are used to calibrate the VITROS® 5.1 FS Chemistry Systems, VITROS® 4600 Chemistry Systems, and VITROS® 5600 Integrated Systems for the quantitative measurement of homocysteine.

The VITROS® Chemistry Products HCY 2 Performance Verifiers I, II and III are prepared from processed human serum to which amino acid and preservative have been added. These are assayed controls used to monitor performance of VITROS® Chemistry Products HCY and VITROS® Chemistry Products HCY 2 Reagents on VITROS® Systems.

The VITROS® Chemistry Products FS Diluent Pack 2 (Saline/BSA) is a common reagent that is used by multiple assays on VITROS® Systems. This is a dual chambered package containing two ready-to-use liquid diluents. Diluent 1 is prepared from processed water to which inorganic salt has been added. Diluent 2 is prepared from processed water to which bovine serum albumin, inorganic salts and preservatives have been added.

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- 6. Device intended
VITROS® Chemistry Products HCY 2 Reagent: For in vitro diagnostic use only. VITROS® Chemistry Products HCY 2 Reagent is used on VITROS® Systems to quantitatively measure total homocysteine concentration in human serum and plasma. Serum and plasma homocysteine levels can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia and homocystinuria.

VITROS® Chemistry Products HCY 2 Performance Verifiers I, II & III: For in vitro diagnostic use only. VITROS® Chemistry Products HCY 2 Performance Verifiers are assayed controls used to monitor performance of VITROS® Chemistry Products HCY and VITROS® Chemistry Products HCY® 2 Reagents on VITROS® Systems.

- 7. Compari-VITROS® Chemistry Products HCY 2 Reagent is substantially equivalent to the VITROS® Chemistry Products HCY Reagent (K061588) (predicate son to predicate device) which was cleared by the FDA for IVD use. devices:
A least squares linear regression analysis using an n=110, demonstrated the following relationship: y = 1.00 x + 0.42 (umol/L) with a correlation coefficient (r) of 0.997 where y = results obtained using the VITROS® Chemistry Products HCY 2 assay and x = results obtained with the commercially available VİTROS® Chemistry Products HCY Assay in conventional/SI units (umol/L) on the VITROS 5,1 FS Chemistry System.

A least squares linear regression analysis using an n=123, demonstrated the following relationship: y = 0.98 x + 0.60 (umol/L) with a correlation coefficient (r) of 0.997 where y = results obtained using the VITROS® Chemistry Products HCY 2 assay on the VITROS® 4600 Chemistry System and x = results obtained with the commercially available VITROS® Chemistry Products HCY Assay in conventional/SI units (umol/L) on the VITROS 5,1 FS Chemistry System.

A least squares linear regression analysis using an n=111, demonstrated the following relationship: y = 0.99 x + 0.46 (umol/L) with a correlation coefficient (r) of 0.993 where y = results obtained using the VITROS® Chemistry Products HCY 2 assay on the VITROS® 5600 Integrated System and x = results obtained with the commercially available VITROS® Chemistry Products HCY Assay in conventional/SI units (umol/L) on the VITROS 5,1 FS Chemistry System.

The VITROS® Chemistry Products HCY 2 Performance Verifiers I, II & III are substantially equivalent to the VITROS® Chemistry Products HCY Performance Verifiers I, II & III (K061588) (predicate device) which was cleared by the FDA for IVD use.

In addition to correlation studies, bench testing was performed to determine assay precision, linearity, specificity, expected values, limit of detection, dilution and specimen matrix of the VITROS® Chemistry Products HCY 2 assay.

VITROS Chemistry Products HCY 2 assay and controls

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Table 1 Similarities and differences of the assays performed using the VITROS® Chemistry Products HCY 2 Reagent and the VITROS® Chemistry Products HCY Reagent.

| Device<br>Characteristic | VITROS® HCY 2 Reagent<br>(New device) | VITROS® HCY Reagent<br>(Predicate device) |
|-----------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For <i>in vitro</i> diagnostic use only.<br>VITROS Chemistry Products<br>HCY 2 Reagent is used on<br>VITROS® Systems to<br>quantitatively measure total<br>homocysteine concentration in<br>human serum and plasma. Serum<br>and plasma homocysteine levels<br>can assist in the diagnosis and<br>treatment of patients suspected of<br>having hyperhomocysteinemia<br>and homocystinuria. | Same, but specific to VITROS<br>Chemistry Products HCY Reagent |
| Reagent Packs | One dual chamber reagent pack<br>containing one reagent in each<br>chamber | Two dual chamber reagent packs<br>containing three reagents, one<br>reagent in each of three chambers |
| Tests per pack/set | 50 tests/reagent pack/ 6 reagent<br>packs/carton=300 tests/carton | 50 tests/ 2 reagent packs/ 6<br>reagent packs/carton=150<br>tests/carton |
| Reactive<br>ingredients | Lactate Dehydrogenase (LDH)=<br>37.9 KU/L<br>Serine=0.8 mmol/L (0.08% w/v)<br>Nicotinamide Adenine<br>Dinucleotide (NADH)=0.5<br>mmol/L (0.03% w/v)<br>Tris (2-Carboxyethyl) phosphine<br>hydrochloride (TCEP)=2.9<br>mmol/L (0.08% w/v)<br>Cystathionine β-lyase=16.4 KU/L<br>Cystathionine β-synthase=0.748<br>KU/L | Lactate Dehydrogenase (LDH)=<br>65 KU/L<br>Serine=1.3 mmol/L (0.01% w/v)<br>Nicotinamide Adenine<br>Dinucleotide (NADH)=0.56<br>mmol/L (0.04% w/v)<br>Tris (2-Carboxyethyl) phosphine<br>hydrochloride (TCEP)=26.3<br>mmol/L (0.8% w/v)<br>Cystathionine β-lyase=16 KU/L<br>Cystathionine β-synthase=22<br>KU/L |
| Analyte measured | Homocysteine | Same |
| Sample Type | Serum and plasma | Same |
| Measurement<br>Type | Quantitative | Same |
| Reportable Range | 2.0-50.0 µmol/L | 1.0-50.0 µmol/L |
| Device<br>Characteristic | VITROS® HCY 2 Reagent<br>(New device) | VITROS® HCY Reagent<br>(Predicate device) |
| Sensitivity (LoQ) | 1.29 µmol/L | 0.96 µmol/L |
| Calibrator levels | Two levels (0, 28 µmol/L) | Same |
| Calibrator format | Liquid | Same |
| Calibrator matrix | Aqueous solution containing<br>amino acids and inorganic acid | Same |
| Instrumentation | Automated clinical chemistry<br>analyzer | Same |
| Calibration<br>Traceability<br>Standard | NIST 1955 | Same |
| Reference Interval | Males: 6.6 – 14.8 µmol/L<br>Females: 4.7 – 12.6 µmol/L | Same |

#### VITROS Chemistry Products HCY 2 assay and controls

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- Table 2 Similarities and differences of the device characteristics between the VITROS® Chemistry Products HCY 2 Performance Verifiers I, II & III with the predicate device VITROS® Chemistry Products HCY Performance Verifiers 1, II & III =

| Device<br>Characteristic | VITROS® HCY 2 Performance<br>Verifiers<br>(New Device) | VITROS® HCY Performance<br>Verifiers<br>(Predicate Device) |
|---------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analytes Reported | Homocysteine in VITROS® HCY<br>and HCY 2 Reagents | Homocysteine in VITROS® HCY<br>Reagent |
| Vial Volume | 1.5 mL/vial | 5 mL/vial |
| Intended Use<br>Statement | For <i>in-vitro</i> diagnostic use only.<br>VITROS® Chemistry Products<br>HCY 2 Performance Verifiers are<br>assayed controls used to monitor<br>performance of VITROS® HCY<br>and VITROS® HCY 2 Reagents<br>on VITROS® Systems. | For <i>in-vitro</i> diagnostic use only.<br>VITROS® Chemistry Products<br>HCY Performance Verifiers are<br>assayed controls used to monitor<br>performance of VITROS® HCY<br>Reagents on VITROS® System. |
| Matrix | The Performance Verifiers are<br>prepared from processed human<br>serum with preservatives added. | Same |
| Product Type | Assayed Control | Same |
| Format | Liquid | Same |
| Number of levels | Three | Same |
| Nominal Values | 7.0, 12.5, and 25 µmol/L | 7.0, 12, and 46 µmol/L |

#### VITROS Chemistry Products HCY 2 assay and controls

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### Conclusions:

The data presented in this premarket notification provide a reasonable assurance that the VITROS® Chemistry Products HCY 2 Reagent and the VITROS® Chemistry Products HCY 2 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 a commercially available assay along with patient samples.

VITROS Chemistry Products HCY 2 assay and controls

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle.

#### Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

May 15, 2013

Ortho-Clinical Diagnostics, Inc. C/O Michael Byrne 100 Indigo Creek Drive ROCHESTER NY 14626-5101

Re: K123930

Trade/Device Name: VITROS® Chemistry Products HCY 2 Reagent, VITROS® Chemistry Products HCY 2 Performance Verifiers I, II & III Regulation Number: 21 CFR 862.1377 Regulation Name: Urinary homocystine (nonquantitative) test system Regulatory Class: II Product Code: LPS, JJX Dated: April 03, 2013 Received: April 04, 2013

Dear Mr. Byrne:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. 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 Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); 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.

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#### Page 2-Mr. Byrne

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

# Carol C. Benson -S for

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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## Indications for Use

| 510(k) Number (if known): | k123930 |
|-----------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name: | VITROS® Chemistry Products HCY 2 Reagent<br>VITROS® Chemistry Products HCY 2 Performance Verifiers I, II, and III |
| Indications for Use: | For <i>in vitro</i> diagnostic use only. VITROS® Chemistry Products HCY 2 Reagent is used on VITROS® Systems to quantitatively measure total homocysteine concentration in human serum and plasma. Serum and plasma homocysteine levels can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia and homocystinuria.<br>For <i>in vitro</i> diagnostic use only. VITROS® Chemistry Products HCY 2 Performance Verifiers are assayed controls used to monitor performance of VITROS® Chemistry Products HCY and VITROS® Chemistry Products HCY 2 Reagents on VITROS® Systems. |
| Prescription Use | X AND/OR Over-The-Counter Use _______ |
| (Part 21 CFR 801 Subpart D) | (21 CFR 807 Subpart C) |

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

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

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Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

| 510(k) | k123930 |
|--------|---------|
|--------|---------|

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