VIDAS B.R.A.H.M.S. PCT ASSAY

K071146 · bioMerieux, Inc. · NTM · Oct 11, 2007 · Microbiology

Device Facts

• Record ID: K071146
• Device Name: VIDAS B.R.A.H.M.S. PCT ASSAY
• Applicant: bioMerieux, Inc.
• Product Code: NTM · Microbiology
• Decision Date: Oct 11, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3210
• Device Class: Class 2

Intended Use

VIDAS® BRAHMS PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma (lithium heparin) using the ELFA (Enzyme-Linked Fluorescent Assay). VIDAS BRAHMS PCT is intended for use in conjunction with othe laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of ICU admission, for progression to severe sepsis and septic shock.

Device Story

The VIDAS BRAHMS PCT is an automated enzyme-linked fluorescent immunoassay (ELFA) performed on VIDAS instruments. It measures procalcitonin (PCT) concentration in human serum or plasma. The device uses a Solid Phase Receptacle (SPR) as both a solid phase and pipetting device. The assay follows a one-step sandwich immunoassay principle: sample and alkaline phosphatase-labeled anti-PCT antibodies are cycled in the SPR; antigen binds to immunoglobulins on the SPR wall and conjugate; unbound compounds are washed away. A substrate (4-Methylumbelliferyl phosphate) is added; the enzyme catalyzes hydrolysis into a fluorescent product (4-Methyl-umbelliferone) measured at 450 nm. Fluorescence intensity is proportional to PCT concentration. Results are automatically calculated via calibration curves and printed. Used in clinical laboratory settings by trained personnel to assist clinicians in assessing the risk of severe sepsis or septic shock in critically ill patients upon ICU admission.

Clinical Evidence

Clinical study of 232 ICU patients (143 male, 89 female; age 18-92). Patients categorized by ACCP/SCCM criteria. Sensitivity/specificity evaluated at 0.5 ng/mL and 2.0 ng/mL cut-offs. At 0.5 ng/mL: 86/104 severe sepsis/septic shock patients correctly identified. At 2.0 ng/mL: 67/104 severe sepsis/septic shock patients correctly identified. Method comparison with predicate (n=204) showed 97.1% concordance at 0.5 ng/mL and 94.1% at 2.0 ng/mL.

Technological Characteristics

Enzyme-Linked Fluorescent Assay (ELFA). Materials: mouse monoclonal anti-human PCT immunoglobulins coated on SPR. Energy: automated instrument-based fluorescence detection at 450nm. Connectivity: standalone VIDAS/miniVIDAS instruments. Calibration: Master Lot Entry (MLE) card for lot-specific master curve, plus two-point recalibration. Sample volume: 200 μL. Assay time: ~20 minutes.

Indications for Use

Indicated for the determination of human procalcitonin in human serum or plasma (lithium heparin) to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock.

Regulatory Classification

Identification

An endotoxin assay is a device that uses serological techniques in whole blood. The device is intended for use in conjunction with other laboratory findings and clinical assessment of the patient to aid in the risk assessment of critically ill patients for progression to severe sepsis.

Special Controls

*Classification.* Class II (special controls). The special control for this device is the FDA guidance entitled “Class II Special Controls Guidance Document: Endotoxin Assay.” See § 866.1(e) for the availability of this guidance document.

Predicate Devices

• BRAHMS PCT LIA Assay

Submission Summary (Full Text)

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K071146

J 1 2007

## 510(k) SUMMARY

# VIDAS® B-R.A.H.M.S PCT Assay

| | A. Submitter Information |
|----------------------|----------------------------------------------------------------------------------|
| Submitter's Name: | bioMérieux, Inc. |
| Address: | 595 Anglum Road<br>Hazelwood, MO 63042 |
| Contact Person: | Nikita S. Mapp |
| Phone Number: | 314-731-7474 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | March 1, 2007 |
| | B. Device Name |
| Trade Name: | VIDAS® BRAHMS PCT |
| Common Name: | Endotoxin Assay |
| Classification Name: | 21 CFR 866.3210, Product Code NTM<br>Antigen, Inflammatory Response Marker, Seps |
| | C. Predicate Device Name |
| Trade Name: | BRAHMS PCT LIA Assay |

### D. Device Description

The VIDAS BRAHMS PCT Assay is an enzyme-linked fluorescent immunoassay (ELFA) performed in an automated VIDAS® instrument.

The assay principle combines a one-step immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), serves as the solid phase as well as the pipetting device for the assay. Reagents for the assay are ready-to-use and pre-dispensed in the sealed reagent strips.

All of the assay steps are performed automatically by the instrument. The sample is transferred into the wells containing anti-procalcitorin antibodies labeled with alkaline phosphatase (conjugate). The sample/conjugate mixture is cycled in and out of the SPR several times. This operation enables the antigen to bind with the immunoglobulins fixed to the interior wall of the SPR and the conjugate to form a sandwich. Unbound compounds are eliminated during washing steps.

Two detection steps are performed successively. During each step, the substrate (4-Methylumbellifery| phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the

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hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the concentration of antigen present in the sample.

At the end of the assay, results are automatically calculated by the instrument in relation to two calibration curves corresponding to the two revelation steps and stored in memory, and then printed out.

### E. Intended Use

VIDAS BRAHMS PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma (lithium heparin) using the ELFA (Enzyme-Linked Fluorescent Assay). VIDAS BRAHMS PCT is intended for use in conjunction with othe laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of ICU admission, for progression to severe sepsis and septic shock.

## F. Technological Characteristics Summary

A comparison of the similarities and differences of the assays is presented in the table below.

| | IDAS BRAHMS PCT | BRAHMS POWER |
|------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Determination of human procalcitonin in<br>human serum or plasma (lithium heparin) | Same |
| Indications for Use | For use in conjunction with other laboratory<br>findings and clinical assessments to aid in<br>the risk assessment of critically ill patients<br>on their first day of ICU admission, for<br>progression to severe sepsis and septic<br>shock | Same |
| Specimen | Human serum or plasma (lithium heparin) | Same |
| Analyte | Measures procalcitonin concentration | Same |
| Antibody | Anti-PCT antibody (monoclonal mouse) | Same |
| Assay Principle | Immunoassay based on sandwich principle | Immunoluminometric assay based<br>on sandwich principle |
| Automated | Automated assay | Non-automated assay |
| Final Detection of PCT<br>antigen | Fluorescence (ELFA) of 4-methyl-<br>umbelliferyl measured at 450 nm | Luminescence signal<br>measurement via luminometer |
| Assay Technique | Enzyme-Linked Fluorescent Assay(ELFA) | Immunoluminometric assay (ILMA) |
| Special instrument<br>requirements | None | Luminometer required |
| Sample Volume | 200 µl | 20 pl |
| Assay Time | ~20 minutes | ~90 minutes |
| Measurement range | 0.05 to 200 ng/ml | 0.3 - 500 ng/ml |
| | Device<br>[VIDAS BRAHMS PCT] | Predicate<br>[BRAHMS PCT LIA] |
| | Non-clinical (Analytical) Comparison | |
| Matrix Comparison | Serum similar to Plasma<br>For a given patient, the same type of<br>sample tube must be performed for each<br>patient | Same |
| Precision/<br>Reproducibility | 6 samples tested in duplicate over 20 days<br>total precision: 6.17 - 15.31% CV<br>intra-run precision: 1.93 - 4.61% CV<br>inter-run precision: 3.57 - 7.04% CV<br>inter-site precision: 4.21 - 11.40% CV | 14 samples tested in duplicate<br>over 20 days<br>total precision: 5.3 - 16.6% CV<br>within run precision: 2.4-10% CV |
| Analytical Detection<br>Limit | <0.05 ng/ml | 1.0 ng/ml |
| Functional Detection<br>Limit | 0.09 ng/ml | 0.3 ng/ml |
| Interfering Substances | No significant interference | No significant interference |
| Bilirubin | 574 µmol/l | 40 mg/dl |
| Hemoglobin | 347 µmol/l | 500 mg/dl |
| Triglycerides | 30 g/l | 634 mg/dl |
| Analytical Specificity | No significant interference | No significant interference |
| Protein (albumin) | 4 g/dl | 1 g/dl |
| Human calcitonin | 60 ng/ml | 8 ng/ml |
| Human katacalcin | 10 ng/ml | 30 ng/ml |
| Human alpha-CGRP | 10 µg/ml | 30 ng/ml |
| Human beta-CGRP | 10 µg/ml | 30 ng/ml |
| Drug Interference | No significant interference | No significant interference |
| Imipenem | 0.5 mg/ml | 1.18 mg/ml |
| Cefotaxime | 180 mg/dl | 90 mg/dl |
| Vancomycin | 3 mg/ml | 3.5 mg/ml |
| Dopamine | 26 mg/dl | 13 mg/dl |
| Noradrenalin | 4 µg/ml | 2 µg/ml |
| Dobutamine | 22.4 µg/ml | 11.2 µg/ml |
| Heparin | 16,000 U/L | 8000 U/I |
| Furosemide | 4 mg/dl | 2 mg/dl |
| Hook Effect | No hook effect found up to concentrations<br>of 2600 ng/ml | No hook effect found up to<br>concentrations of 4000 µg/L |
| | Clinical Comparison | |
| Cut-off | >2 ng/ml = high risk of severe sepsis<br>and/or septic shock<br><0.5 ng/ml = low risk of severe sepsis<br>and/or septic shock | Same |
| | Clinical Sensitivity/Specificity Studies | |
| Number of patients | 232 patients | 179 patients |
| Study Site(s) | US and Europe | Europe |
| Results | → In 92 patients with PCT level ≤0.5<br>ng/ml, 18 patients had severe sepsis or<br>septic shock<br>→ In 104 patients with severe sepsis or<br>septic shock, 37 patients had PCT | → In 44 patients with PCT<br><0.5 ng/ml, no patient had<br>severe sepsis or septic shock<br>→ In 77 patients with severe<br>sepsis or septic shock, one |
| Test | Device<br>[VIDAS BRAHMS PCT] | Predicate<br>[BRAHMS PCT LIA] |
| | | ng/ml |
| | Clinical Specificity Study on U.S. Healthy Subjects (normal values) | |
| Number of patients | 200 healthy subjects | 144 healthy subjects |
| Study Site(s) | US | US |
| Results | 200 healthy subjects;<br>95th percentile: <0.05 ng/ml cut-off<br>99th percentile: 0.09 ng/ml | 143 out of 144 healthy subjects<br>had PCT values of <0.3 ng/ml |

#### G. Performance Data

A summary of the non-clinical and clinical test results is presented in the table below.

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## H. Conclusion

The VIDAS® BRAHMS PCT Assay is substantially equivalent to the BRAHMS PCT LIA Assay.

The 510(k) summary includes only information that is also covered in the body of the 510(k). The summary does not contain any puffery or unsubstantiated labeling claims. The summary does not contain any raw data, i.e., contains only summary data. The summary does not contain any trade secret or confidential commercial information. The summary does not contain any patient identification information.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like symbol with three curved lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the bird symbol. The text is in all capital letters and is evenly spaced around the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Nikita S. Mapp Senior Regulatory Affairs Specialist bioMérieux, Inc. 595 Anglum Road Hazelwood, MO 63042

OCT 1 1 2007

Re: k071146

> Trade/Device Name: VIDAS® BRAHMS PCT Regulation Number: 21 CFR 866.3210 Regulation Name: Endotoxin Assay Regulatory Class: Class II Product Code: NTM Dated: August 30, 2007 Received: September 4, 2007

Dear Ms. Mapp:

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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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 advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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/industry/support/index.html.

Sincerely yours.

Sally attym

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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VIDAS® B.R.A.H.M.S PCT Assay Traditional 510(k) Submission

## INDICATIONS FOR USE

510(k) Number (if known): K071146

Device Name: VIDAS BRAHMS PCT Assay

Indications for Use: VIDAS® BRAHMS PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma (lithium heparin) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. The VIDAS BRAHMS PCT assay is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of ICU admission, for progression to severe sepsis and septic shock.

Prescription Use_ × (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH. Office of Device Evaluation (ODE)

Kudith te Poole

**Division Sign-Off**

Office of In Vitro Diagnostic Device Evaluation and Safety