(265 days)
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.
The Atellica™ IM Folate Assay is an immunoassay with the following components: Atellica™ IM Folate Primary Reagent ReadyPack (including Lite Reagent, Solid Phase Reagent, and Folate Binding Protein), Atellica™ IM Folate Calibrator (including Low and High Calibrators), Atellica IM Folate DTT/Releasing Agent (sold separately, including Dithiothreitol and Sodium hydroxide), and Atellica IM RBC Folate (sold separately, including Lyophilized ascorbic acid and RBC Folate Ascorbic Acid Diluent).
The provided text is a 510(k) summary for an in vitro diagnostic device (Atellica™ IM Folate Assay), not an AI/ML medical device. Therefore, much of the requested information regarding AI/ML device acceptance criteria and study design (such as multi-reader multi-case studies, expert adjudication, training set ground truth, etc.) is not applicable to this document.
However, I can extract information related to the acceptance criteria for this diagnostic assay and how its performance was proven.
Here's a summary based on the provided document, addressing the applicable points:
Device Name: Atellica™ IM Folate Assay
Indications for Use: 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.
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a singular table, but rather presents performance characteristics of the device, implying that the observed performance met internal or regulatory (CLSI) standards. The predicate device (ADVIA Centaur Folate Assay, K010050) serves as the benchmark for substantial equivalence.
Here's a compilation of key performance characteristics, acting as de-facto acceptance criteria for a new in vitro diagnostic assay, and the reported performance. The "Acceptance Criteria" here are implicitly derived from CLSI guidelines and comparison to the predicate.
| Performance Characteristic | Implicit/Stated Acceptance Criteria (often based on CLSI guidelines or predicate performance) | Reported Device Performance (Atellica™ IM Folate Assay) |
|---|---|---|
| Precision (Repeatability CV) | Acceptable Coefficient of Variation (CV) for different analyte levels (e.g., typically <10% for low concentrations, <5% for higher) | Serum Control 1: 3.3% Serum Control 2: 2.5% Serum 1: N/A Serum 2: 2.4% Serum 3: 2.9% Serum 4: 2.6% (Similar data for Whole Blood samples) |
| Precision (Within-Lab CV) | Acceptable Coefficient of Variation (CV) | Serum Control 1: 6.1% Serum Control 2: 6.4% Serum 1: N/A Serum 2: 5.9% Serum 3: 5.9% Serum 4: 6.5% (Similar data for Whole Blood samples) |
| Linearity (Serum) | Bias from linear fit estimate <10% across the measuring range. | Bias from linear fit estimate <10% (except sample E with 10.44% and G with -8.27% but still within reasonable limits for biological assays). Assay linear from 0.56 to 24 ng/mL. |
| Linearity (RBC) | Linear relationship with previously cleared device's values. | Linear relationship between 0.98 to 17.51 ng/mL. |
| Dilution Recovery | Recoveries generally close to 100% (e.g., 90-110%). | Recoveries ranged from 102.6%-110.0% (mean 105.4%). |
| Spiking Recovery | Recoveries generally close to 100% (e.g., 90-110%). | Recoveries ranged from 87%-116% (mean 104%). |
Method Comparison (Correlation r) | High correlation coefficient (e.g., r > 0.95) with predicate device. | Serum: r = 0.99 RBC hemolysate: r = 0.93 |
| Method Comparison (Regression Equation) | Slope and intercept close to 1 and 0, respectively, when compared to predicate. | Serum: y = 0.94x - 0.01 ng/mL RBC hemolysate: y = 1.06x – 2.52 ng/mL |
| Detection Limits (LoB, LoD, LoQ) | Values demonstrated to be fit for clinical purpose. | Serum: LoB 0.19 ng/mL, LoD 0.38 ng/mL, LoQ 0.56 ng/mL RBC: LoB 0.00 ng/mL, LoD 0.21 ng/mL, LoQ 0.56 ng/mL |
| Interference | No significant interference (<10% effect) from common endogenous and exogenous substances at specified concentrations. | No indication of interference (< 10% effect) up to the claimed interferent levels for all tested substances. |
| Cross-Reactivity | Low cross-reactivity (e.g., ≤ 5%) with related compounds. | Amethopterin: ≤2% Aminopterin: ≤1% Folinic Acid: <4% |
| Shelf-life Stability | Stable until expiration date under specified storage. | Stable until expiration date printed on carton @ 2-8 °C. |
| On-board Stability | Stable for specified duration on the analyzer. | 14 days; pack calibration interval of 7 days, lot calibration interval of 14 days. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Study:
- Serum: 4 human serum samples + 2 control levels. Tested 80 times each (N=80).
- Whole Blood: 5 whole blood samples + 2 control levels. Tested 80 times each (N=80).
- Provenance: Not explicitly stated, but typically clinical samples from a diverse patient population within the manufacturer's operational regions (often global or US/EU). Implied to be retrospective for the testing as the samples are "tested".
- Linearity Study:
- Serum: 9 samples (prepared from high and low human serum pools). Each tested in triplicate.
- RBC: 11 samples (prepared from previously cleared device's values).
- Dilution Recovery: 5 human serum samples. Each run in triplicate.
- Spiking Recovery: 5 samples (human serum pools with added folate stock).
- Method Comparison:
- Human Serum: 105 samples.
- Human Whole Blood: 100 samples.
- Provenance: Not explicitly stated, but clinical samples.
- Collection Tube Comparison: 90 samples (K2 EDTA Whole Blood vs. Lithium Heparin Whole Blood).
- Reference Intervals Verification:
- Serum: 30 serum samples from apparently healthy individuals.
- RBC: 25 RBC samples (whole blood with tested percent hematocrit) from apparently healthy individuals.
- Detection Limits: Not specified as a sample size, but uses CLSI EP17-A2 protocol, which involves multiple replicates of blank, low-concentration, and standard samples.
- Interference: Two human sample pools (one approx. 4.0 ng/mL Folate, second approx. 12.0 ng/mL Folate). Both spiked with potential interferents.
- Cross-Reactivity: Normal human serum sample and blank assay diluent for each test compound. Multiple replicates processed.
Data Provenance: Not explicitly stated as "country of origin," but given it's a Siemens Healthcare Diagnostics product, it's likely multi-site clinical samples, possibly from North America and/or Europe. The studies are described as lab-based performance studies using human samples, fitting a retrospective data collection model for the test set.
3. Number of Experts Used to Establish Ground Truth and Qualifications
This section is not applicable as this is an in vitro diagnostic assay for quantitative determination of an analyte (folate) using chemical/immunological reactions, not an AI/ML device requiring interpretation of complex images or data by human experts. The "ground truth" for this device is the actual concentration of folate in the samples, determined either by highly accurate reference methods or by comparison to an established, legally marketed predicate device (ADVIA Centaur Folate assay).
4. Adjudication Method for the Test Set
Not applicable. As a quantitative in vitro diagnostic device, there is no need for expert adjudication. The result is a numerical concentration.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
Not applicable. MRMC studies are specific to AI/ML devices that assist human readers in interpreting medical images or other complex data. This is a lab-based immunoassay.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Applicable, but in a different context. The "standalone" performance for this device refers to the ability of the Atellica IM Analyzer and reagents to accurately and precisely measure folate concentration without human intervention influencing the measurement itself (beyond loading samples and initiating tests). The performance characteristics listed (precision, linearity, detection limits, etc.) are all measures of the standalone analytical performance of the device.
7. The Type of Ground Truth Used
The ground truth for this in vitro diagnostic device is established using:
- Reference Methods/Internal Standards: Traceability is stated as being to an "internal standard manufactured using highly purified material (N-5-methyl tetrahydrofolate)." Calibrator values are traceable to this standardization.
- Comparison to a Legally Marketed Predicate Device: The primary method for demonstrating substantial equivalence is by comparing performance (method comparison studies) to the existing, FDA-cleared ADVIA Centaur Folate Assay (K010050). The predicate's results serve as a de-facto "ground truth" for demonstrating equivalence in clinical performance.
- Known Concentrations: For studies like linearity, dilution, spiking, and detection limits, samples with pre-defined or precisely measured concentrations are used as ground truth.
- Clinically Defined Samples: Healthy donor samples for reference interval verification.
8. The Sample Size for the Training Set
Not applicable in the AI/ML context. This is not an AI/ML device that undergoes a "training" phase with a dataset. The "training" for such an in vitro diagnostic device involves the manufacturer's internal development and optimization of the assay formulation, reagents, and instrument parameters to achieve desired performance, not data-driven model training.
9. How the Ground Truth for the Training Set was Established
Not applicable for an AI/ML training set. For the development of the assay itself, the ground truth for optimizing the assay would involve various analytical chemistry techniques and reference materials to ensure the assay accurately measures folate, coupled with comparison to existing validated methods or the predicate device during development phases.
{0}------------------------------------------------
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
{1}------------------------------------------------
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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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
{2}------------------------------------------------
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) | |
|---|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) | ☐ |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
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 DaruwalaRegulatory Affairs Senior Specialist |
|---|---|
| Address: | Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591 |
| Phone: | 914-524-2812 |
914-524-3579 Fax:
Email: darius.daruwala@siemens.com
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.
{4}------------------------------------------------
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.
{5}------------------------------------------------
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
| Item | Atellica™ IM Folate Assay(Candidate Device) | ADVIA Centaur Folate Assay(Predicate Device)(K010050) |
|---|---|---|
| Intended Use | For in vitro diagnostic use in thequantitative determination of folate inserum or red blood cells using theAtellica™ IM analyzer. Folic acidmeasurements are used in thediagnosis and treatment of anemias. | For in vitro diagnostic use in thequantitative determination of folatein serum or red blood cells using theADVIA Centaur system. |
| Instrument | Atellica IM | ADVIA Centaur |
| Measurement | Quantitative | Same |
| Methodology | Chemiluminescence | Same |
| Assay Protocol | Competitive immunoassay | Same |
| Traceability/Standardization | Internal standards. Values have beenassigned to correlate to the Predicatedevice. | Same |
| Specimen Type | Human Serum,Red Blood Cells (RBC) | Same |
| Lower Limit ofMeasuring Range | LoQ | Analytical Sensitivity |
| Sample Volume | 100 µL | 150 µL |
| Reagents | Lite Reagent: Folate labeled withacridinium ester (~9.8 ng/mL) in Buffer;bovine serum albumin; sodium azide(0,1%) and preservatives.Solid Phase Reagent: Buffered avidin(~20 µg/mL) covalently coupled toparamagnetic particles in buffer;human serum albumin andpreservatives.Folate Binding Protein: Purified folatebinding protein (~1.0 µg/mL) covalentlycoupled to biotin in buffer; bovineserum 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 |
{6}------------------------------------------------
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)
{7}------------------------------------------------
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(ng/mL)(nmol/L)(%) | CVc(%) | SD(ng/mL)(nmol/L) | CV(%) | ||
| 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 | ExpectedDose(ng/mL) | ObservedDose(ng/mL) | Recovery(Observed vsExpected) | Linear FitEstimate | Deviationfrom LinearFit(%) | Deviationfrom LinearFit(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
{8}------------------------------------------------
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 | ExpectedDose(ng/mL) | ObservedDose (ng/mL) | Recovery(Observed vsExpected) | Linear FitEstimate | Deviationfrom LinearFit(%) | Deviationfrom LinearFit(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):
{9}------------------------------------------------
510(k) Summary
| Specimen Type | ComparisonAssay (x) | N | r | Regression Equation | Sample Range |
|---|---|---|---|---|---|
| Serum | ADVIA CentaurFOL | 105 | 0.99 | $y = 0.94x - 0.01$ ng/mL | 0.64–22.78 ng/mL |
| RBChemolysate | ADVIA CentaurFOL | 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, WholeBlood | 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
{10}------------------------------------------------
510(k) Summary
of interference (< 10% effect) up to the interferent levels claimed. Results are presented below.
| Interferent | Concentrations Showing noSignificant 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(ng/mL) | Maximum ObservedCross-Reactivity (%) |
|---|---|---|
| Amethopterin | 150 | ≤2% |
| Aminopterin | 75 | ≤1% |
| Folinic Acid | 25 | <4% |
{11}------------------------------------------------
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.
§ 862.1295 Folic acid test system.
(a)
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.(b)
Classification. Class II.