Atellica IM Folate Assay

K172201 · Siemens Healthcare Diagnostics, Inc. · CGN · Apr 12, 2018 · Clinical Chemistry

Device Facts

• Record ID: K172201
• Device Name: Atellica IM Folate Assay
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: CGN · Clinical Chemistry
• Decision Date: Apr 12, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1295
• Device Class: Class 2

Intended Use

The Atellica™ Folate assay is for in vitro diagnostic use in the quantitative determination of folate in serum or red blood cells using the Atellica IM Analyzer. Folic acid measurements are used in the diagnosis and treatment of anemias.

Device Story

The Atellica IM Folate assay is an in vitro diagnostic test for quantitative folate measurement in human serum or red blood cells. It utilizes a competitive chemiluminescent immunoassay protocol on the Atellica IM Analyzer. The assay uses folate labeled with acridinium ester, paramagnetic particles coated with avidin, and biotin-coupled folate binding protein. The system processes patient samples to produce a quantitative result, which is used by clinicians to diagnose and manage anemias. The device is intended for use in clinical laboratory settings by trained laboratory personnel. The output provides a numerical concentration value, assisting healthcare providers in assessing patient folate status and guiding clinical decision-making regarding anemia treatment.

Clinical Evidence

Bench testing only. Precision study (20-day, CLSI EP5-A3) evaluated 4 serum and 5 whole blood samples across 3 reagent lots, showing CVs generally <8%. Linearity confirmed across claimed ranges (serum 0.56–24 ng/mL; RBC 0.98–17.51 ng/mL). Method comparison (n=105 serum, n=100 RBC) against predicate showed high correlation (r=0.99 for serum, r=0.93 for RBC). Interference testing evaluated endogenous substances and biotin; cross-reactivity evaluated for amethopterin, aminopterin, and folinic acid.

Technological Characteristics

Competitive chemiluminescent immunoassay. Reagents: acridinium-ester-labeled folate, avidin-coupled paramagnetic particles, biotin-labeled folate binding protein. Form factor: liquid reagents for automated analyzer. Connectivity: integrated with Atellica IM Analyzer. Standards: CLSI EP06-A, EP05-A3, EP07-A2, EP17-A2, EP28-A3.

Indications for Use

Indicated for the quantitative determination of folate in serum or red blood cells to aid in the diagnosis and treatment of anemias in patients.

Regulatory Classification

Identification

A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow.

Predicate Devices

• ADVIA Centaur Folate Assay (k010050)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the logo for the U.S. Food & Drug Administration (FDA). The logo consists of two parts: on the left is the Department of Health & Human Services logo, and on the right is the FDA logo. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

April 12, 2018

Siemens Healthcare Diagnostics Inc. Darius Daruwala Senior Specialist, Regulatory Affairs 511 Benedict Avenue Tarrytown, NY 10591

Re: K172201

Trade/Device Name: Atellica IM Folate Assay Regulation Number: 21 CFR 862.1295 Regulation Name: Folic acid test system Regulatory Class: Class II Product Code: CGN Dated: February 28, 2018 Received: March 1, 2018

## Dear Darius Daruwala:

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 and Part 809); medical device 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

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Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Kellie B. Kelm -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) K172201

Device Name Atellica™ IM Folate Assay

Indications for Use (Describe)

The Atellica™ Folate assay is for in vitro diagnostic use in the quantitative determination of folate in serum or red blood cells using the Atellica IM Analyzer. Folic acid measurements are used in the diagnosis and treatment of anemias.

Type of Use (Select one or both, as applicable)

| Prescription Use (Part 21 CFR 801 Subpart D) | <span> <svg height="12" width="12"> <path d="M1 1 L11 11 M1 11 L11 1" stroke="black"></path> </svg> </span> |
|----------------------------------------------|-------------------------------------------------------------------------------------------------------------|
| Over-The-Counter Use (21 CFR 801 Subpart C) | <span>☐</span> |

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This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92 and the Safe Medical Device Act of 1990.

The assigned 510(k) Number is: K172201

### Date Prepared 1.

April 12, 2018

### 2. Applicant Information

| Contact: | Darius Daruwala<br>Regulatory Affairs Senior Specialist |
|----------|-----------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics Inc.<br>511 Benedict Avenue<br>Tarrytown, NY 10591 |
| Phone: | 914-524-2812 |

914-524-3579 Fax:

Email: [e-mail]

### Regulatory Information 3.

## Table 1. Regulatory Information for Atellica™ IM Folate Assay

| Trade Name | Atellica™ IM Folate Assay |
|---------------------|--------------------------------------|
| Model Numbers | 10995572 (1-pack); 10995573 (5-pack) |
| Common Name | Immunoassay, Folate |
| Classification Name | Folic Acid Test System |
| FDA Classification | Class II |
| Review Panel | Clinical Chemistry (75) |
| Product Code | CGN |
| Regulation Number | 862.1295 |

### Predicate Device Information 4.

## ADVIA Centaur Folate

Predicate Device Name: ADVIA Centaur Folate 510(k) Number: K010050

### 5. Intended Use / Indications for Use

## Atellica™ IM Folate

The Atellica™ IM Folate assay is for in vitro diagnostic use in the quantitative determination of folate in serum or red blood cells using the Atellica™ IM Analyzer. Folic acid measurements are used in the diagnosis and treatment of anemias.

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### Device Description 6.

## Table 3. Summary of Ingredients of the Atellica™ IM Folate Assay Components

| Component | Volume | Ingredients |
|-----------------------------------------------------------------------|--------------|-----------------------------------------------------------------------------------------------------------------------------------------------|
| Atellica™ IM Folate Primary Reagent ReadyPack (included in assay kit) | | |
| Atellica™ IM Folate Lite Reagent | 10.0 mL/pack | Folate labeled with acridinium ester (~9.8 ng/mL) in buffer; bovine serum albumin; sodium azide (0.1%); preservatives |
| Atellica™ IM Folate Solid Phase Reagent | 20.0 mL/pack | Purified avidin (~20 µg/mL) covalently coupled to paramagnetic particles in buffer; human serum albumin; preservatives |
| Atellica™ IM Folate Binding Protein | 10.0 mL/pack | Purified folate binding protein (~1.0 µg/mL) covalently coupled to biotin in buffer; bovine serum albumin; preservatives |
| Atellica™ IM Folate Calibrator (included in assay kit) | | |
| Atellica™ IM Folate Low and High Calibrators | 3.0 mL/vial | After reconstitution, low or high levels of N-5-methyltetrahydrofolic acid; buffer; human serum albumin; sodium azide (< 0.1%); preservatives |
| Atellica IM Folate DTT/Releasing Agent (sold separately) | | |
| Atellica IM Folate DTT | 8.0 mL/vial | Dithiothreitol (~95 mg/mL in liquid form) |
| Atellica IM Folate Releasing Agent | 4.0 mL/vial | Sodium hydroxide (~1.1 N) |
| Atellica IM RBC Folate (sold separately) | | |
| RBC Folate Ascorbic Acid | ~0.30 g/vial | Lyophilized ascorbic acid |
| RBC Folate Ascorbic Acid Diluent | 30.0 mL/vial | Bovine serum albumin; buffer; sodium azide (<0.1%) |

### Purpose of the Submission 7.

The purpose of this submission is a premarket notification for a new device: Atellica™ IM Folate assay.

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### 8. Substantial Equivalence Information

Predicate Device Name: ADVIA Centaur Folate Assay 510(k) Number: K010050

## Table 4. Comparison of Atellica™ IM Folate Assay to Predicate

| <b>Item</b> | Atellica™ IM Folate Assay<br>(Candidate Device) | ADVIA Centaur Folate Assay<br>(Predicate Device)<br>(K010050) |
|-----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For <i>in vitro</i> diagnostic use in the<br>quantitative determination of folate in<br>serum or red blood cells using the<br>Atellica™ IM analyzer. Folic acid<br>measurements are used in the<br>diagnosis and treatment of anemias. | For <i>in vitro</i> diagnostic use in the<br>quantitative determination of folate<br>in serum or red blood cells using the<br>ADVIA Centaur system. |
| Instrument | Atellica IM | ADVIA Centaur |
| Measurement | Quantitative | Same |
| Methodology | Chemiluminescence | Same |
| Assay Protocol | Competitive immunoassay | Same |
| Traceability/<br>Standardization | Internal standards. Values have been<br>assigned to correlate to the Predicate<br>device. | Same |
| Specimen Type | Human Serum,<br>Red Blood Cells (RBC) | Same |
| Lower Limit of<br>Measuring Range | LoQ | Analytical Sensitivity |
| Sample Volume | 100 µL | 150 µL |
| Reagents | Lite Reagent: Folate labeled with<br>acridinium ester (~9.8 ng/mL) in Buffer;<br>bovine serum albumin; sodium azide<br>(0,1%) and preservatives.<br>Solid Phase Reagent: Buffered avidin<br>(~20 µg/mL) covalently coupled to<br>paramagnetic particles in buffer;<br>human serum albumin and<br>preservatives.<br>Folate Binding Protein: Purified folate<br>binding protein (~1.0 µg/mL) covalently<br>coupled to biotin in buffer; bovine<br>serum albumin and preservatives | Same |
| Measuring Range | Serum: 0.56 – 24 ng/mL | 0.35 - 24 ng/mL |
| | RBC: 0.98 – 17.51 ng/mL | 0.35 - 24 ng/mL |
| Calibration | 2-point calibration | Same |

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### Standard/Guidance Document References 9.

The following recognized standards from Clinical Laboratory Standards Institute (CLSI) were used as a basis of the study procedures described in this submission:

- Evaluation of Precision of Quantitative Measurement Procedures: Approved S Guideline - Third Edition (CLSI EP05-A3, 2014; Recognition Number 7-251)
- S Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline (CLSI EP06-A, 2003; Recognition Number 7-193)
- S Interference Testing in Clinical Chemistry: Approved Guideline - Second Edition (CLSI EP07-A2, 2005; Recognition Number 7-127)
- S Measurement Procedure Comparison And Bias Estimation Using Patient Samples --Third Edition (CLSI EP9-A3, 2013; Recognition Number 7-245)
- S Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline -- Second Edition (CLSI EP17-A2, 2013; Recognition Number 7-233)
- S Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory: Approved Guideline - Third Edition (CLSI EP28-A3c - formerly C28-A3c, 2010; Recognition Number 7-224)
- S Medical devices – Application of risk management to medical devices (ANSI/AAMI/ISO 14971:2007/(R)2010; Recognition Number 5-70)

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### 10. Performance Characteristics

### 10.1 Precision

A 20-day precision study was performed according to CLSI EP5-A3. Four human serum and five whole blood samples and two levels of controls were tested.

| | | Repeatability | | | Within-Lab | | | | |
|-----------------------|----|---------------|----------|-----------------------------------|------------|---------------------------|-----------|--------|-----|
| Sample | Na | (ng/mL) | (nmol/L) | SDb<br>(ng/mL)<br>(nmol/L)<br>(%) | CVc<br>(%) | SD<br>(ng/mL)<br>(nmol/L) | CV<br>(%) | | |
| Serum Control 1 | 80 | 2.82 | 6.39 | 0.09 | 0.20 | 3.3 | 0.17 | 0.39 | 6.1 |
| Serum Control 2 | 80 | 5.43 | 12.30 | 0.14 | 0.32 | 2.5 | 0.35 | 0.79 | 6.4 |
| Serum 1 | 80 | 1.42 | 3.22 | 0.05 | 0.11 | N/Ad | 0.08 | 0.18 | N/A |
| Serum 2 | 80 | 4.13 | 9.35 | 0.10 | 0.23 | 2.4 | 0.24 | 0.54 | 5.9 |
| Serum 3 | 80 | 6.19 | 14.02 | 0.18 | 0.41 | 2.9 | 0.36 | 0.82 | 5.9 |
| Serum 4 | 80 | 9.23 | 20.91 | 0.24 | 0.54 | 2.6 | 0.60 | 1.36 | 6.5 |
| Whole Blood Sample 1 | 80 | 94.89 | 214.93 | 4.56 | 10.33 | N/A | 6.55 | 14.84 | N/A |
| Whole Blood Sample 2 | 80 | 153.11 | 346.79 | 4.40 | 9.97 | 2.9 | 11.21 | 25.39 | 7.3 |
| Whole Blood Sample 3 | 80 | 362.58 | 821.24 | 9.82 | 22.24 | 2.7 | 19.99 | 45.28 | 5.5 |
| Whole Blood Sample 4 | 80 | 563.94 | 1277.32 | 19.34 | 43.81 | 3.4 | 35.18 | 79.68 | 6.2 |
| Whole Blood Sample 5 | 80 | 899.24 | 2036.78 | 45.66 | 103.42 | 5.1 | 62.92 | 142.51 | 7.0 |
| Whole Blood Control 1 | 80 | 77.24 | 174.95 | 2.68 | 6.07 | N/A | 5.48 | 12.41 | N/A |
| Whole Blood Control 2 | 80 | 257.52 | 583.28 | 6.51 | 14.75 | 2.5 | 16.84 | 38.14 | 6.5 |

a Number of samples tested

b Standard deviation

c Coefficient of variation

d Not applicable; there is no CV requirement at these concentrations

### 10.2 Linearity

## Serum:

A linearity study was performed according to CLSI EP06-A using 9 samples spanning the assay range, which were prepared using high and low human serum pools. The mean was taken from each sample tested in triplicate. As presented below, the bias from the linear fit estimate was <10%. The assay is linear from 0.56 to 24 ng/mL.

| Sample | Expected<br>Dose<br>(ng/mL) | Observed<br>Dose<br>(ng/mL) | Recovery<br>(Observed vs<br>Expected) | Linear Fit<br>Estimate | Deviation<br>from Linear<br>Fit<br>(%) | Deviation<br>from Linear<br>Fit<br>(ng/mL) |
|--------|-----------------------------|-----------------------------|---------------------------------------|------------------------|----------------------------------------|--------------------------------------------|
| A | 0.46 | 0.46 | 100% | 0.21 | 116.71 | 0.25 |
| B | 1.26 | 1.12 | 89% | 0.98 | 13.93 | 0.14 |
| C | 2.05 | 1.81 | 88% | 1.75 | 3.38 | 0.06 |
| D | 2.84 | 2.57 | 90% | 2.52 | 1.99 | 0.05 |
| E | 3.63 | 3.63 | 100% | 3.29 | 10.44 | 0.34 |
| F | 8.83 | 7.99 | 90% | 8.34 | -4.17 | -0.35 |
| G | 14.03 | 12.28 | 87% | 13.38 | -8.27 | -1.11 |
| H | 19.24 | 18.09 | 94% | 18.43 | -1.85 | -0.34 |
| I | 24.44 | 24.44 | 100% | 23.48 | 4.07 | 0.96 |

The weighted linear regression equation is presented below.

Observed = 0.971(Expected) - 0.237 ng/mL

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# 510(k) Summary

## RBC:

A linearity study was performed according to CLSI EP06-A using 11 samples spanning the assay range. Using a previously cleared red blood cell Folate device's values as expected values when analyzing the results obtained from the Atellica IM rFOL method results in a linear relationship between the measuring interval 0.98 to 17.51 ng/mL.

| Sample | Expected<br>Dose<br>(ng/mL) | Observed<br>Dose (ng/mL) | Recovery<br>(Observed vs<br>Expected) | Linear Fit<br>Estimate | Deviation<br>from Linear<br>Fit<br>(%) | Deviation<br>from Linear<br>Fit<br>(ng/mL) |
|--------|-----------------------------|--------------------------|---------------------------------------|------------------------|----------------------------------------|--------------------------------------------|
| P01 | 0.98 | 1.37 | 139% | 1.50 | -8.7% | 0.13 |
| P02 | 6.73 | 7.38 | 110% | 6.77 | 9.0% | -0.61 |
| P03 | 9.58 | 9.82 | 103% | 9.38 | 4.7% | -0.44 |
| P04 | 11.49 | 11.06 | 96% | 11.13 | -0.6% | 0.07 |
| P05 | 12.81 | 11.60 | 91% | 12.34 | -6.0% | 0.74 |
| P06 | 13.82 | 12.07 | 87% | 13.27 | -9.1% | 1.21 |
| P07 | 14.96 | 14.03 | 94% | 14.32 | -2.0% | 0.29 |
| P08 | 15.28 | 14.99 | 98% | 14.61 | 2.6% | -0.39 |
| P09 | 16.05 | 15.46 | 96% | 15.31 | 1.0% | -0.15 |
| P10 | 16.63 | 15.89 | 96% | 15.85 | 0.3% | -0.04 |
| P11 | 17.51 | 17.45 | 100% | 16.65 | 4.8% | -0.80 |

The linear regression equation is presented below.

Observed = 0.917(Expected) - 0.596 ng/mL

### 10.3 Dilution Recovery

Five human serum samples were diluted 1:2 using Atellica IM Folate diluent and assayed for recovery. All samples were run in triplicate. The recoveries ranged from 102.6%-110.0% with a mean of 105.4%.

#### Spiking Recovery 10.4

Five samples were created by adding a fixed volume of Folate stock solution into human serum pools. Five control samples were created by pipetting an equal volume of DI H2O into each of the patient sample control for dilution. The percent recovery was calculated with Observed concentration vs. Expected concentration. The recoveries ranged from 87%-116% with a mean of 104%.

### 10.5 Method Comparison

Method Comparison studies were done with 105 human serum and 100 human whole blood samples distributed over the assay range to demonstrate equivalence to the Predicate (ADVIA Centaur Folate). The Atellica IM Folate assay shows good correlation in sample results compared to the Predicate. The regression equations from the analysis are presented below.

Atellica IM FOL (y) vs ADVIA Centaur FOL (x) (Weighted Deming regression):

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# 510(k) Summary

| Specimen Type | Comparison<br>Assay (x) | N | r | Regression Equation | Sample Range |
|-------------------|-------------------------|-----|------|--------------------------|----------------------|
| Serum | ADVIA Centaur<br>FOL | 105 | 0.99 | $y = 0.94x - 0.01$ ng/mL | 0.64–22.78 ng/mL |
| RBC<br>hemolysate | ADVIA Centaur<br>FOL | 100 | 0.93 | $y = 1.06x – 2.52$ ng/mL | 229.66-2264.56 ng/mL |

### 10.6 Collection Tube Comparison

Specimen equivalency was determined using weighted Deming linear regression in accordance to CLSI Document EP09-A3. The following results were obtained:

| Specimen (y) | Reference Specimen (x) | Regression Equation | Sample Interval | N |
|-------------------------|-----------------------------|---------------------------|------------------------|----|
| K2 EDTA, Whole<br>Blood | Lithium Heparin Whole Blood | $y = 1.02x – 32.86$ ng/mL | 432.70 - 1103.69 ng/mL | 90 |

### 10.7 Reference Intervals

Reference intervals for the Atellica IM Folate assay were verified to confirm the already established ranges on ADVIA Centaur Assay according to CLSI EP28-A3c. A total of 30 serum and 25 RBC (whole blood with tested percent hematocrit) samples from apparently healthy individuals were analyzed. Based on a 95% confidence interval, the following reference intervals were verified.

| Category | N | Median (ng/mL) | 95th Percentile Range (ng/mL) |
|--------------|-----|----------------|-------------------------------|
| Serum folate | | | |
| Normal | 305 | 12.51 | > 5.38 |
| RBC folate | | | |
| Normal | 286 | 425 | 280 - 791 |

As with all in vitro diagnostic assays, each laboratory should determine its own reference interval for the diagnostic evaluation of patient results.

### 10.8 Detection Limits

The limit of blank (LoB), limit of detection (LoD), and the limit of quantitation (LoQ) were determined as described in CLSI protocol EP17-A2. The LoB is defined as the highest measurement result that is likely to be observed for a blank sample. The LoD is defined as the lowest concentration of Folate that can be detected with 95% probability. The LoQ is defined as the lowest concentration of Folate that can be detected at a total CV of 20%.

The Atellica IM Folate assay has an LoB of 0.19 ng/mL, an LoD of 0.38 ng/mL, and an LoQ of 0.56 ng/mL for serum and an LoB of 0.00 ng/mL, an LoD of 0.21 ng/mL, and an LoQ of 0.56 ng/mL for RBC hemolysate.

#### 10.9 Interference

Interference studies were performed according to CLSI EP07-A2 to evaluate the performance of the Atellica IM Folate assay in the presence of endogenous and other interfering substances. Two human sample pools were tested. One sample pool had approximately 4.0 ng/mL Folate. The second sample pool had approximately 12.0 ng/mL Folate. These sample pools were spiked with potential interferents. There was no indication

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## 510(k) Summary

of interference (< 10% effect) up to the interferent levels claimed. Results are presented below.

| | Interferent | Concentrations Showing no<br>Significant Interference |
|------------|------------------------|-------------------------------------------------------|
| Endogenous | Conjugated Bilirubin | 20 mg/dL |
| | Lipemia (intralipid) | 2000 mg/dL |
| | Unconjugated Bilirubin | 20 mg/dL |
| | Biotin, serum | 50 ng/mL |
| | Biotin, whole blood | 75 ng/mL |
| Exogenous | Acetaminophen | 200 mg/dL |
| | Acetylsalicylic Acid | 1000 mg/dL |
| | Ibuprofen | 50 mg/dL |
| | Acetylcysteine | 566 mg/dL |
| | Ampicillin-Na | 1000 mg/dL |
| | Cefoxitin | 660 mg/dL |
| | Cyclosporine | 5 mg/dL |
| | Doxycyclin | 50 mg/dL |
| | Levodopa | 20 mg/dL |
| | Methyldopa | 20 mg/dL |
| | Metronidazole | 200 mg/dL |
| | Phenylbutazone | 40 mg/dL |
| | Rifampicin | 60 mg/dL |
| | Theophylline | 10 mg/dL |
| | Ascorbic Acid | 44 mg/dL |

### Cross-Reactivity 10.10

Cross reactivity was evaluated in the Atellica IM Folate immunoassay using a normal human serum sample and blank assay diluent for each test compound. An aliquot of each sample was spiked with test compound so that the final test sample contained the compound at the required concentration. A second aliquot of the base pool is spiked with just the diluent to serve as a control sample. Multiple replicates of the test and control samples were processed. Cross-reactivity was calculated as the % difference between the mean test and control sample results, with respect to the test compound concentration. Results are presented below.

| Cross-Reactant | Cross-Reactant Concentration<br>(ng/mL) | Maximum Observed<br>Cross-Reactivity (%) |
|----------------|-----------------------------------------|------------------------------------------|
| Amethopterin | 150 | ≤2% |
| Aminopterin | 75 | ≤1% |
| Folinic Acid | 25 | <4% |

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### 10.11 Traceability and Stability

## Traceability

The Atellica IM Fol assay is traceable to an internal standard manufactured using highly purified material (N-5-methyl tetrahydrofolate). Assigned values for calibrators are traceable to this standardization.

### Stability

## Shelf-life:

Unopened Atellica IM Folate reagents and calibrators are stable until expiration date printed on the carton when stored at 2-8 °C.

## On-board:

The onboard stability of the Atellica IM Folate reagents is 14 days with a pack calibration interval of 7 days, and a lot calibration interval of 14 days.

#### 10.12 Proposed Labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

### Conclusion 11.

Based on the results of comparative testing, the new Atellica IM Folate assay is substantially equivalent in principle and performance to the currently-marketed predicate device, the ADVIA Centaur Folate assay, cleared under 510(k) k010050.