ARCHITECT SIROLIMUS ASSAY

K070822 · Fujirebio Diagnostics,Inc. · NRP · Sep 28, 2007 · Clinical Toxicology

Device Facts

• Record ID: K070822
• Device Name: ARCHITECT SIROLIMUS ASSAY
• Applicant: Fujirebio Diagnostics,Inc.
• Product Code: NRP · Clinical Toxicology
• Decision Date: Sep 28, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3840
• Device Class: Class 2

Indications for Use

The ARCHITECT Sirolimus assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sirolimus in human whole blood on the ARCHITECT i System. The ARCHITECT Sirolimus assay is to be used as an aid in the management of renal transplant patients receiving sirolimus therapy. The ARCHITECT Sirolimus Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of sirolimus in human whole blood. The ARCHITECT Sirolimus Whole Blood Precipitation Reagent is for the extraction of sirolimus from samples (human whole blood patient specimens, controls, and ARCHITECT Sirolimus Calibrators) to be tested on the ARCHITECT i System.

Device Story

The ARCHITECT Sirolimus assay is an in vitro diagnostic test for measuring sirolimus levels in human whole blood. The process begins with a manual pretreatment step where whole blood is extracted using a precipitation reagent, heated, and centrifuged. The resulting supernatant is loaded onto the ARCHITECT i System. The system performs a chemiluminescent microparticle immunoassay (CMIA) where sirolimus in the sample competes with acridinium-labeled conjugate for binding sites on anti-sirolimus coated paramagnetic microparticles. The system measures the resulting chemiluminescent reaction as relative light units (RLUs), which are inversely proportional to the sirolimus concentration. Used in clinical and hospital laboratories by trained personnel, the assay provides quantitative results to assist healthcare providers in managing immunosuppressive therapy for renal transplant patients, helping to optimize dosing and monitor patient safety.

Clinical Evidence

Clinical performance was evaluated using human whole blood specimens from renal transplant patients. Regression analysis (Passing-Bablok) comparing ARCHITECT Sirolimus to the IMx predicate (n=168) showed a slope of 1.05 and correlation coefficient of 0.94. Comparison against LC/MS/MS (n=167) showed a slope of 1.18 and correlation coefficient of 0.91. Precision studies (CLSI EP5-A2) demonstrated total CV ≤ 10%. Linearity, analytical sensitivity (LOD 0.3 ng/mL), and interference testing were performed to validate assay performance within the 2-30 ng/mL reportable range.

Technological Characteristics

CMIA technology using anti-sirolimus mouse monoclonal antibody-coated paramagnetic microparticles in MES buffer. Conjugate consists of sirolimus-acridinium in citrate buffer. Precipitation reagent contains zinc sulfate, DMSO, and ethylene glycol. System is an automated, networked clinical laboratory analyzer. Software performs automated RLU measurement and concentration calculation via calibration curve.

Indications for Use

Indicated for quantitative determination of sirolimus in human whole blood as an aid in the management of renal transplant patients receiving sirolimus therapy.

Regulatory Classification

Identification

A sirolimus test system is a device intended to quantitatively determine sirolimus concentrations in whole blood. Measurements are used as an aid in management of transplant patients receiving therapy with sirolimus.

Special Controls

*Classification.* Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Sirolimus Test Systems.” See § 862.1(d) for the availability of this guidance document.

Predicate Devices

• ABBOTT IMx® Sirolimus Microparticle Enzyme Immunoassay (K042411)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized graphic on the left and the company name on the right. The graphic is a black and white abstract shape. The text "FUJIREBIO" is in bold, black letters, and the text "Diagnostics, Inc" is in a smaller, regular font below the company name.

# 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: k070822

SEF 2 8 2007

# Submitter Information

| Address: | Fujirebio Diagnostics, Inc.<br>201 Great Valley Parkway<br>Malvern, PA 19355 |
|----------|------------------------------------------------------------------------------|
|----------|------------------------------------------------------------------------------|

| Contact person: | Diana L. Dickson |
|-----------------|------------------|
| | [phone] |
| | [e-mail] |

Summary preparation date: September 28, 2007

## Name of Device

| Trade/Proprietary Name: | ARCHITECT Sirolimus Assay |
|-------------------------|---------------------------------|
| | ARCHITECT Sirolimus Calibrators |

NRP

DLJ

Common/Usual Name: Sirolimus Test Systems Calibrator

21 CFR 862.3840 Regulation Number: 21 CFR 862.3200

Requlatory Class: Class II

Product Code:

# Predicate Device

ABBOTT IMx® Sirolimus Microparticle Enzyme Immunoassay (K042411)

## Device Description

The ARCHITECT Sirolimus assay is a delayed one-step immunoassay for the quantitative determination of sirolimus in human whole blood using CMIA technology with flexible assay protocols, referred to as Chemiflex.

Prior to the initiation of the automated ARCHITECT sequence, a manual pretreatment step is performed in which the whole blood sample is extracted with a precipitation reagent, heated,

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Image /page/1/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized graphic on the left, followed by the company name in two lines of text. The first line reads "FUJIREBIO" in bold, sans-serif font, and the second line reads "Diagnostics, Inc" in a smaller, regular font.

and centrifuged. The supernatant is decanted into a Transplant Pretreatment Tube, which is placed onto the ARCHITECT i System.

Sample, assay diluent, and anti-sirolimus coated paramagnetic microparticles are combined to create a reaction mixture. Sirolimus present in the sample binds to the anti-sirolimus coated microparticles. After a delay, sirolimus acridinium-labeled conjugate is added to the reaction mixture. The sirolimus acridinium-labeled conjucate competes for the available binding sites on the anti-sirolimus coated paramagnetic microparticles. Following an incubation, the microparticles are washed, and pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs),

An indirect relationship exists between the amount of sirolimus in the RLUs detected by the ARCHITECT i System optics.

## Reportable Range

The reportable range for the ARCHITECT Sirolimus assay is 2 ng/mL (minimum reportable value based on Functional Sensitivity) to 30 ng/mL.

## Intended Use

## Reagent Kit

The ARCHITECT Sirolimus assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sirolimus in human whole blood on the ARCHITECT i System. The ARCHITECT Sirolimus assay is to be used as an aid in the management of renal transplant patients receiving sirolimus therapy.

# Calibrator Kit

The ARCHITECT Sirolimus Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of sirolimus in human whole blood.

## Whole Blood Precipitation Reagent

The ARCHITECT Sirolimus Whole Blood Precipitation Reagent is for the extraction of sirolimus from samples (human whole blood patient specimens, controls, and ARCHITECT Sirolimus Calibrators) to be tested on the ARCHITECT i System.

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Image /page/2/Picture/1 description: The image shows the logo for "FUJIREBIO Diagnostics, Inc". The logo consists of a stylized graphic on the left, followed by the company name in bold, sans-serif font. Below the company name, the words "Diagnostics, Inc" are written in a smaller, regular font.

# Statement of Substantial Equivalence

The ARCHITECT Sirolimus assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sirolimus in human whole blood on the ARCHITECT i System. The ARCHITECT Sirolimus assay is to be used as an aid in the management of renal transplant patients receiving sirolimus therapy.

The ARCHITECT Sirolimus assay is substantially equivalent to the IMx Sirolimus assay. Both of the devices are IVD products and are indicated for the quantitative determination of sirolimus in human whole blood and used as an aid in the management of renal transplant patients receiving sirolimus therapy.

A study was performed using human whole blood specimens from renal transplant patients receiving sirolimus therapy, where regression analysis was performed using the Passing-Bablok' method. Data from the study are summarized in the following table.

| ARCHITECT Sirolimus vs. IMx Sirolimus | | | |
|---------------------------------------|-------------------------|------------------------|----------------------------|
| Number of<br>Observations | Intercept<br>(95% CIa) | Slope<br>(95% CI) | Correlation<br>Coefficient |
| 168 | 0.12<br>(-0.38 to 0.47) | 1.05<br>(1.00 to 1.11) | 0.94 |

ª Confidence Interval Specimen Range (ARCHITECT): 2.1 ng/mL - 29.7 ng/mL Specimen Range (IMx): 1.8 ng/mL - 29.6 ng/mL

Additional testing of the above sample was completed with LC/MS/MS, where regression analysis was performed using the Passing-Bablok1 method. Data from the study are summarized in the following table.

| ARCHITECT Sirolimus vs. LC/MS/MS | | | |
|----------------------------------|--------------------------|------------------------|----------------------------|
| Number of<br>Observations | Intercept<br>(95% CI) | Slope<br>(95% CI) | Correlation<br>Coefficient |
| 167 | -0.37<br>(-0.89 to 0.12) | 1.18<br>(1.11 to 1.27) | 0.91 |

Specimen Range (ARCHITECT): 2.1 nq/mL - 29.7 ng/mL Specimen Range (LC/MS/MS): 1.65 ng/mL - 29.1 ng/mL

^&#x27; Passing H, Bablok W. A new biometrical procedure for testing the equality of measurements from two different analytical methods. J Clin Chem Clin Biochem 1983; 21(11)709-20.

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Image /page/3/Picture/1 description: The image shows the logo for "FUJIREBIO Diagnostics, Inc." The logo consists of a stylized graphic on the left, followed by the company name in bold, black letters. Below the company name, the words "Diagnostics, Inc" are written in a smaller, non-bold font. The graphic on the left appears to be a stylized representation of three overlapping shapes, with the left shape being solid black and the right shape being filled with vertical lines.

A comparison of the features of the ARCHITECT Sirolimus assay and the IMx Sirolimus assay are as follows:

| Similarities | | |
|------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | ARCHITECT Sirolimus<br>(Proposed Device) | IMx Sirolimus<br>(Predicate Device)<br>K042411 |
| Device Type | In vitro diagnostic | In vitro diagnostic |
| Classification and<br>Product Code | Class II, NRP | Class II, NRP |
| Product Usage | Clinical and Hospital laboratories | Clinical and Hospital laboratories |
| Intended Use | Quantitative determination of<br>sirolimus in human whole blood as<br>an aid in the management of renal<br>transplant patients receiving<br>sirolimus therapy. | Quantitative determination of<br>sirolimus in human whole blood as<br>an aid in the management of renal<br>transplant patients receiving<br>sirolimus therapy. |
| Type of Specimen | Human Whole Blood | Human Whole Blood |
| Specimen Collection<br>Method | EDTA Whole Blood Collection<br>Tubes | EDTA Whole Blood Collection<br>Tubes |
| Specimen Pretreatment<br>Step | Manual extraction of sirolimus in<br>human whole blood | Manual extraction of sirolimus in<br>human whole blood |
| Calibrators | 6 Levels (0 - 30 ng/mL) | 6 Levels (0 - 30 ng/mL) |
| Calibrator Matrix | Processed human whole blood | Processed human whole blood |
| Antibody | Mouse monoclonal (anti -<br>sirolimus) | Mouse monoclonal (anti -<br>sirolimus) |
| Interpretation of Results | Calibrator Curve<br>An indirect relationship exists<br>between the amount of sirolimus in<br>the sample and the light detected<br>by the instrument system | Calibrator Curve<br>An indirect relationship exists<br>between the amount of sirolimus in<br>the sample and the light detected<br>by the instrument system |

| | Differences | |
|------------------------|-------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------|
| | ARCHITECT Sirolimus<br>(Proposed Device) | IMx Sirolimus<br>(Predicate Device)<br>K042411 |
| Instrument System | ARCHITECT System | IMx System |
| Principle of Operation | Chemiluminscent Microparticle<br>Immunoassay (CMIA) | Microparticle Enzyme<br>Immunoassay (MEIA) |
| Conjugate | Sirolimus-Acridinium Conjugate in<br>citrate buffer | Sirolimus-alkaline phosphatase in<br>TRIS buffer with protein stabilizers |
| Microparticles | Anti-sirolimus (mouse,<br>monoclonal) coated paramagnetic<br>microparticles in MES buffer | Anti-sirolimus (mouse monoclonal)<br>coated polystyrene latex<br>microparticles in TRIS buffer |
| Precipitation Reagent | Zinc sulfate solution in DMSO and<br>Ethylene glycol | Zinc sulfate solution in methanol<br>and Ethylene glycol |

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Image /page/4/Picture/1 description: The image contains the logo for "FUJIREBIO Diagnostics, Inc". The logo consists of a stylized graphic to the left of the text. The graphic is a combination of black and white shapes, with a pattern of vertical lines on the right side. The text "FUJIREBIO" is in bold, and "Diagnostics, Inc" is in a smaller font size below it.

## Performance Characteristics

## Precision:

A study was performed with the ARCHITECT Sirolimus assay based on guidance from the Clinical and Laboratory Standards Institute, document (CLSI, formerly NCCLS) Protocol EP5-A2. Abbott Immunosuppressent-MCC (levels 1, 2) and five whole blood panels were assayed, using two lots of reagents, on two instruments, in replicates of two at two separate times per day for 20 days. Each reagent lot used a single calibration curve throughout the study.

The total precision %CV of the ARCHITECT Sirolimus assay was determined to be less than or equal to 10%.

## Linearity:

A dilution linearity study was performed by diluting high concentration sirolimus whole blood specimens with the ARCHITECT Sirolimus Calibrator A. The concentration of sirolimus was determined for each dilution of sample and the mean percent (%) recovery was calculated.

The ARCHITECT Sirolimus assay was determined to have a mean recovery within 10% of the expected result for diluted samples.

#### Functional Sensitivity:

Whole blood specimens were spiked with sirolimus to achieve approximate concentrations from 0.1 to 5.3 ng/mL and tested in replicates of 10, twice a day, for five days. At the upper 95% confidence limit, the lowest ARCHITECT Sirolimus assay value exhibiting a 20% CV was calculated to be 0.7 ng/mL, which is below the reportable range of the ARCHITECT Sirolimus assay.

#### Analytical Sensitivity:

The limit of detection for the ARCHITECT Sirolimus assay, defined as the concentration at two standard deviations above the ARCHITECT Sirolimus Calibrator A (0.0 ng/mL) was calculated to be 0.3 ng/mL, which is below the reportable range of the ARCHITECT Sirolimus assay at 95% confidence (based on one study with n=24 runs, 10 replicates calibrator A and 4 replicates calibrator B per run).

#### Interference:

Whole blood specimens were supplemented with various drugs and potentially interfering compounds (triglycerides, hematocrit, bilirubin, total protein, cholesterol, uric acid, HAMA, and rheumatoid factor [RF]). The average recovery observed during the study ranged from 95 to 106%.

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Image /page/5/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized graphic on the left, followed by the company name in two lines of text. The graphic is a geometric shape with black and white sections, while the text is in a simple, sans-serif font.

# Specificity:

Aliquots of whole blood specimens were augmented with sirolimus, targeting values ranging from 5 to 22 ng/mL. These five specimens were spiked with cross-reactant solution. Data from this study are summarized in the following table.

| Metabolite | Amount<br>Added<br>(ng/mL) | Mean Excess<br>Concentration<br>Detected<br>(ng/mL, n=5) | % Cross<br>Reactivity |
|---------------------------------------------------------------------|----------------------------|----------------------------------------------------------|-----------------------|
| F2 (41-0-demethyl-hydroxyl-<br>sirolimus) | 10 | 0.87 | 8.7 |
| F3 (41-0-demethyl-hydroxyl<br>sirolimus; 7-0-demethyl<br>sirolimus) | 3 | 0.12 | 7.6 |
| F4 (11-hydroxy-sirolimus) | 10 | 3.7 | 36.8 |
| F5 (41-0-demethyl-sirolimus) | 10 | 2.0 | 20.3 |

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# DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle. The eagle is black, and the text is in a smaller font size.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 2 8 2007

Fujirebio Diagnostics, Inc c/o Ms. Diana Dickson 201 Great Valley Parkway Malvern, PA 19355

Re: k070822

Trade/Device Name: ARCHITECT Sirolimus Assay Regulation Number: 21 CFR 862.3840 Regulation Name: Sirolimus test system Regulatory Class: Class II Product Code: NRP, JIT Dated: September 14, 2007 Received: September 17, 2007

Dear Ms. Dickson:

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 af 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 your device 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 tolli the [phone] or [phone] or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Jean M. Coopes, M.S., D.V.M.

Yéan M. Cooper, M.S., 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): K070822

Device Name: ARCHITECT Sirolimus

Indications For Use:

#### Reagent Kit

The ARCHITECT Sirolimus assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sirolimus in human whole blood on the ARCHITECT i System. The ARCHITECT Sirolimus assay is to be used as an aid in the management of renal transplant patients receiving sirolimus therapy.

#### Calibrator Kit

The ARCHITECT Sirolimus Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of sirolimus in human whole blood.

#### Whole Blood Precipitation Reagent

The ARCHITECT Sirolimus Whole Blood Precipitation Reagent is for the extraction of sirolimus from samples (human whole blood patient specimens, controls, and ARCHITECT Sirolimus Calibrators) to be tested on the ARCHITECT i System.

Sean Cooper
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Satety

510(k) 070822

Prescription Use ﺮﺍ (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 In Vitro Diagnostic Devices (OIVD)

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