K Number
K051292
Date Cleared
2005-06-17

(30 days)

Product Code
Regulation Number
862.1295
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

Elecsys RBC Folate Hemolyzing Reagent is used together with the Elecsys Folate II assay for the quantitative determination of folate in erythrocytes (RBC folate).

Binding assay for the in vitro quantitative determination of folate in human serum. Measurements obtained by this devices are used in the diagnosis and treatment of anemias.

The binding assay is intended for use on the Roche Elecsys 2010 and MODULAR ANALYTICS E170 (Elecsys module) immunoassay analyzers.

Device Description

The Elecsys RBC Folate Hemolyzing Reagent is an ascorbic acid solution with which whole blood treated with anticoagulants (heparin or EDTA) is diluted. After incubation the erythrocytes are lysed and intracellular folate is liberated and stabilized. The hemolysate is then used as a prediluted sample for subsequent measurement in the Elecsys Folate II assay.

AI/ML Overview

The provided document describes the Elecsys RBC Folate Hemolyzing Reagent. However, it does not include detailed acceptance criteria or a study designed to explicitly prove the device meets specific acceptance criteria in the way a diagnostic accuracy or comparative effectiveness study would.

Instead, this 510(k) summary focuses on demonstrating substantial equivalence to a predicate device (Elecsys Red Blood Cell Folate Lysing Reagent, K981931). The "Device Comparison" table highlights similarities and differences, implying that the modified device's performance characteristics (like precision and stability) are considered acceptable by being comparable to or improved over the predicate.

Given the information provided, I will construct a response based on the comparisons made in the document rather than a formal acceptance criteria study.


Here's an analysis based on the provided text, addressing your questions where possible:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in the format of a clinical trial's pre-defined thresholds for success. Instead, the performance is reported as a comparison to a predicate device, implying that the modified device's performance is deemed acceptable if it is similar to or improved over the predicate.

Performance MetricPredicate Device (Elecsys Red Blood Cell Folate Lysing Reagent, K981931)Modified Device (Elecsys RBC Folate Hemolyzing Reagent)Implied "Acceptance"
Intended UseQuantitative determination of folate in human red blood cells.Same (Quantitative determination of folate in erythrocytes [RBC folate]).Same, ensuring clinical utility is maintained.
Test PrincipleCompetitive chemiluminescenceSameNo change in underlying analytical methodology.
Sample TypeWhole blood, heparinized or EDTASameCompatibility with standard blood collection methods.
Sample / Lysing1:31SameConsistent sample preparation protocol.
Reagent Ratio
Measuring RangeNot providedUp to 1407 nmol/L (620 ng/mL) without considering hematocrit.The modified device provides a specified measuring range, which implies it's within clinically relevant levels.
Pretreatment Incubation90 minutes ± 15SameConsistent workflow and stability during sample preparation.
Stability - Ascorbic Acid7 days14 daysImprovement: Extended stability simplifies usage and potentially reduces waste.
Stability - Whole blood at room temp4 hours, 1 day (additional text unclear, potentially referring to refrigerated)2 hours (room temp), Same (for 1 day, likely refrigerated interpretation).Potential change: Room temperature stability for whole blood is 2 hours, compared to 4 hours. This is a functional difference to note.
Stability - Hemolysate at room tempNot recommended3.5 hoursImprovement: Hemolysate stability at room temperature adds flexibility for sample handling.
Expected ValuesN=111, 342 - 786 ng/ml(US) N=105, 342 - 786 ng/ml; (Europe) N=282, 176 - 589 ng/ml.Reference ranges are established for different populations, consistent with clinical practice.
Precision (2010 Analyzer)6.5% CV @ 469 ng/ml; 4.8% CV @ 850 ng/ml6.8% CV @ 478 ng/ml; 6.6% CV @ 573 ng/ml; 5.5% CV @ 623 ng/ml.Comparable precision at different concentrations, demonstrating analytical reliability.
Precision (E170 Analyzer)Not applicable (not tested or reported for predicate)9.5% CV @ 188 ng/ml; 6.1% CV @ 312 ng/ml; 3.6% CV @ 410 ng/ml.Demonstrates performance on an additional analyzer, expanding utility.

Study to Prove Acceptance Criteria:

The document describes a substantial equivalence comparison study rather than a study designed to meet specific acceptance criteria for a novel device. The goal was to show the new "Elecsys RBC Folate Hemolyzing Reagent" is as safe and effective as the previously cleared "Elecsys Red Blood Cell Folate Lysing Reagent (K981931)".

2. Sample Size Used for the Test Set and Data Provenance

  • Expected Values:
    • US Population: N=105
    • European Population: N=282
  • Precision (2010 Analyzer): N=63 (Whole blood)
  • Precision (E170 Analyzer): N/A (Number of samples for E170 precision is not explicitly stated, only resultant CVs across multiple concentrations.)
  • Data Provenance: Not explicitly stated, but the mention of both "US" and "Europe" for expected values suggests multinational data collection. The study is implicitly retrospective, as it compares the new device's performance to existing predicate data and uses samples to generate new performance characteristics.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts

This type of information is not applicable to this submission. The device is a diagnostic assay for measuring folate levels. "Ground truth" in this context would refer to the true folate concentration in a sample, which is determined by the analytical method itself or by a reference method. It does not involve expert interpretation or consensus in the way an imaging or pathology study would.

4. Adjudication Method for the Test Set

Not applicable. See point 3.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This device is a laboratory reagent, not an AI-assisted diagnostic tool that involves human readers/interpreters.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

The "standalone" performance for such an assay refers to its analytical performance characteristics (like precision, accuracy, measuring range, stability). These are precisely what are reported in the comparison table, such as:

  • Measuring range of up to 1407 nmol/L.
  • Precision (CV%) values on both Elecsys 2010 and E170 analyzers.
  • Stability data for ascorbic acid, whole blood, and hemolysate.

These are intrinsic analytical characteristics of the device itself.

7. The Type of Ground Truth Used

For folate assays, "ground truth" typically means the established, measured concentration of folate in a sample. This is not "expert consensus," "pathology," or "outcomes data." It's based on analytical measurement compared to a known standard or a reference method. The "expected values" are derived from healthy populations (reference ranges) rather than an individual "ground truth" for each sample.

8. The Sample Size for the Training Set

Not applicable. This device is an immunoassay reagent, not a machine learning or AI-based algorithm that requires a "training set" in the computational sense. The data presented are for performance validation.

9. How the Ground Truth for the Training Set Was Established

Not applicable. See point 8.

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Ko5/292

JUN 1 7 2005

510(k) Summary – Elecsys RBC Folate Hemolyzing Reagent


IntroductionAccording to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence
Submittername, address,contactRoche Diagnostics9115 Hague RdIndianapolis IN 46250(317) 521-3544
Contact person: Kay A. Taylor
Date prepared: May 17, 2005
Device NameProprietary name: Elecsys RBC Folate Hemolyzing Reagent
Common name: Folate Assay
Classification name: Acid, Folic, Radioimmunoassay
DevicedescriptionThe Elecsys RBC Folate Hemolyzing Reagent is an ascorbic acid solutionwith which whole blood treated with anticoagulants (heparin or EDTA) isdiluted. After incubation the erythrocytes are lysed and intracellular folate isliberated and stabilized. The hemolysate is then used as a prediluted samplefor subsequent measurement in the Elecsys Folate II assay.
Intended useElecsys RBC Folate Hemolyzing Reagent is used together with the ElecsysFolate II assay for the quantitative determination of folate in erythrocytes(RBC folate).
PredicateDeviceWe claim substantial equivalence to the Elecsys Red Blood Cell FolateLysing Reagent currently marketed on the Elecsys 2010 and MODULARANALYTICS E170. (K981931).

:

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510(k) Summary – Elecsys RBC Folate Hemolyzing Reagent, continued

Device Comparison The table below illustrates the similarities between the Elecsys Red Blood Cell Folate Lysing Reagent (K981931) and the Elecsys RBC Folate Hemolyzing Reagent (modified device).

TopicElecsys Red Blood Cell FolateLysing Reagent (K981931)Elecsys RBC Folate HemolyzingReagent (Modified Device)
Intended UseThe Elecsys Red Blood Cell FolateLysing Reagent to be used in combinationwith the Elecsys Folate Assay for thequanitation of folate in human red bloodcells.Elecsys RBC Folate Hemolyzing Reagentis used together with the Elecsys Folate IIassay for the quantitative determination offolate in erythrocytes (RBC folate).
Test PrincipleCompetitive chemiluminescenceSame
Sample TypeWhole blood, heparinized or EDTASame
Sample / LysingReagent Ratio1:31Same
Measuring rangeNot providedWithout considering the hematocrit value:up to 1407 nmol/L (620 ng/mL)
Pretreatmentincubation90 minutes ± 15Same
StabilityAscorbic Acid7 days14 days
Whole blood at -room temp4 hours1 day2 hoursSame
Hemolysate at- room tempnot recommended3.5 hours
Expected ValuesN=111, 342 - 786 ng/ml(US) N=105, 342 - 786 ng/ml(Europe) N=282, 176 - 589 ng/ml
PrecisionModified NCCLS (N=60) Whole blood2010 analyzer6.5% CV @ 469 ng/ml4.8% CV @ 850 ng/mlModified NCCLS (N=63) Whole blood2010 analyzer6.8% CV @ 478 ng/ml6.6% CV @ 573 ng/ml5.5% CV @ 623 ng/mlE170 analyzer9.5% CV @ 188 ng/ml6.1% CV @ 312 ng/ml3.6% CV @ 410 ng/ml

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/2/Picture/2 description: The image is a black and white seal for the Department of Health & Human Services USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. In the center of the seal is a stylized image of an eagle.

JUN 17 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Kay A. Taylor MT(ASCP), RAC Regulatory Affairs Principal Roche Diagnostics Corp. 9115 Hague Road Indianapolis, IN 46250

K051292 Re:

Trade/Device Name: Roche Elecsys Folate II Immunoassay Regulation Number: 21 CFR 862.1295 Regulation Name: Folic acid test system Regulatory Class: Class II Product Code: CGN Dated: May 17, 2005 Received: May 18, 2005

Dear Ms. Taylor:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becemined 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 conninered prior to may 20, 2011 accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). and Cosmetic (110. (110.) that as nevice, subject to the general controls provisions of the Act. The r ou may, dierelove, mains of the Act include requirements for annual registration, listing of general voltable provided ing, 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 it may be subject to back dational denal 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 I lease of acrised that I Drimination that your device complies with other requirements of the Act that I Dr Hab Intact and regulations administered by other Federal agencies. You must or any I each 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 CFR Part 807), tacemis 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) I me letter will and it your te 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 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 (240) 276-0484. 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 toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Carol C. Benson

Carol C. Benson, M.A. Acting 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

12051292 510(k) Number (if known):

Device Name: Roche Elecsys Folate II Immunoassay

Indications For Use:

Binding assay for the in vitro quantitative determination of folate in human serum. Dinding assurements obtained by this devices are used in the diagnosis and treatment of anemias.

The binding assay is intended for use on the Roche Elecsys 2010 and MODULAR ANALYTICS E170 (Elecsys module) immunoassay analyzers.

Prescription Use XX : (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)

signature

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Division Slan-C

Office of In Vitro Diaan Device Evaluation

510(k) K051292

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§ 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.