(47 days)
Assay for the in vitro quantitative determination of folate in human serum. The visual "ECLIA" is intended for use on the Boehringer Mannheim Elecsys assay analyzers.
The Elecsys® test principle is based on the sandwich principle. Total duration of assay: 18 minutes.
● 1st Incubation (9 min.): By incubating the sample (15 µl) with the folate pretreatment 1 (15 µl) and pretreatment 2 (10 µl), bound folate is liberated into the serum.
● 2nd Incubation (9 min.): By incubating the pretreated sample with the Ruthenylated folate binding protein (80 µl), an FBP-folate complex is formed, the amount of which is dependent upon the analyte concentration in the sample.
● 3rd incubation (9 min.): after the addition of streptavidin-coated microparticles (30 µl) and folate labeled with biotin (50 µl), the unbound sites of the Ruthenylated folate binding protein become occupied, with formation of a Ruthenylated folate binding protein-folate biotin complex. The entire complex becomes bound to the solid phase via interaction of biotin and streptavidin.
The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed by washing with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame). Results are determined via a calibration curve which is instrument-specific generated by 2-point calibration and a master curve provided via the reagent bar code.
The Boehringer Mannheim Elecsys® FOLATE device is an electrochemiluminescent assay for the in vitro quantitative determination of folate in human serum. The study conducted to demonstrate its substantial equivalence focused on various performance aspects compared to a predicate device, the Bio-Rad Quantaphase II® B12/FOLATE Radioassay (K935286).
Here's a breakdown of the requested information:
Acceptance Criteria and Reported Device Performance
The provided 510(k) summary describes the types of studies performed but does not explicitly list numerical acceptance criteria or specific quantitative performance values for each criterion. It broadly states that studies were performed to evaluate precision, lower detection limit, linearity, correlation, and interference.
If this were a more detailed submission, the table below would contain specific targets (acceptance criteria) and the actual results from the Elecsys® FOLATE device. Based on the provided text, we can infer the categories of acceptance criteria that were likely in place, which would be met if the results were comparable or better than the predicate.
| Acceptance Criteria Category (Inferred) | Reported Device Performance (General Statement from 510(k)) |
|---|---|
| Precision (e.g., CV% within certain limits) | Evaluated according to NCCLS recommendations. |
| Lower Detection Limit (e.g., specific concentration) | Determined. |
| Linearity (e.g., R² value or range of linearity) | Demonstrated. |
| Correlation with Predicate Device (e.g., regression coefficient, R-value) | Correlation study performed with the predicate device. |
| Interference (e.g., % recovery with interferents) | Evaluation of the effect of various endogenous substances (biotin, triglyceride, lipemia, and rheumatoid factor) and commonly used pharmaceutical compounds. |
| Serum Sample Comparison | Performed. |
| Stability (e.g., shelf life, open-vial stability) | Studies performed. |
Study Information
The 510(k) summary provides limited detail on specific study parameters beyond the types of studies conducted.
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Sample sizes used for the test set and the data provenance: The document does not specify the sample sizes used for the various studies (precision, linearity, correlation, interference, stability). The provenance of the data (country of origin, retrospective or prospective) is also not explicitly stated. However, given it's an in vitro diagnostic device for use in human serum, it is highly likely that human serum samples were used, and such studies are typically performed prospectively or with carefully selected retrospective samples.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts: This device is an in vitro diagnostic for quantitative determination of a biomarker (folate). For such devices, the "ground truth" is typically established by reference assays or methods, often highly accurate laboratory methods, rather than clinical expert consensus on diagnostic images or patient presentations. Therefore, the concept of "experts establishing ground truth" in the way it applies to image recognition or clinical diagnosis by human interpretation is not directly applicable here. The "experts" would be laboratory scientists or technicians qualified to perform the reference assays. The document does not specify the number or qualifications of individuals involved in generating reference values.
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Adjudication method for the test set: Not applicable for this type of in vitro diagnostic device, as ground truth is established by laboratory measurement, not by human interpretation requiring adjudication.
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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: This is not applicable. The Elecsys® FOLATE device is an automated in vitro diagnostic assay, not an AI-assisted diagnostic tool that aids human readers in interpreting clinical cases.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Yes, in essence, the Elecsys® FOLATE assay is a standalone algorithm/device in that it provides a quantitative result without direct human interpretation being part of the primary output. The device itself performs the electrochemical detection and provides a numerical folate concentration. The "performance" evaluated in the studies (precision, linearity, correlation) would represent this standalone performance.
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The type of ground truth used:
- For precision, lower detection limit, linearity, and stability, the "ground truth" is typically derived from internal laboratory standards, known concentrations, and repeated measurements to assess the device's inherent analytical performance.
- For correlation with the predicate device, the "ground truth" for the comparative performance would be the results obtained from the Bio-Rad Quantaphase II® B12/FOLATE Radioassay (K935286) when analyzing the same samples.
- For interference studies, the ground truth would be the expected result of the folate measurement in the absence of the interfering substance, or the recovery of a known amount of folate in the presence of the interferent.
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The sample size for the training set: The 510(k) summary does not provide information on a training set sample size. For in vitro diagnostic assays as described, the concept of a "training set" in the context of machine learning (where an algorithm learns from data) is not directly applicable. The device's operating characteristics (algorithms for signal processing, calibration curves) are typically established during development and validated through the performance studies mentioned, rather than 'training' on a dataset in the AI sense.
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How the ground truth for the training set was established: As the device doesn't involve a machine learning "training set" in the conventional sense, this question is not applicable. The analytical methods and parameters are developed and optimized by the manufacturer using internal validation processes.
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DUPLICATE
510(k) Summary
NOV 1 2 1997
| According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. | |
|---|---|
| -- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
BOEHRINGER MANNHEIM CORPORATIONinduction
| 1) Submitter name, address, contact | Boehringer Mannheim Corporation4300 Hacienda DrivePleasanton, CA 94588-2722(510) 730-8215Contact Person: Patricia M. KlimleyDate Prepared: September 24, 1997 |
|---|---|
| 2) Device name | Proprietary name: Elecsys® FOLATECommon name: Electrochemiluminescent assay for the determination of FOLATE.Classification name: Folate Test System. |
| 3) Predicate device | We claim substantial equivalence to the Bio-Rad Quantaphase II® B12/FOLATE Radioassay (K935286). |
| 4) Device Description | The Elecsys® test principle is based on the sandwich principle. Total duration of assay: 18 minutes.● 1st Incubation (9 min.): By incubating the sample (15 µl) with the folate pretreatment 1 (15 µl) and pretreatment 2 (10 µl), bound folate is liberated into the serum.● 2nd Incubation (9 min.): By incubating the pretreated sample with the Ruthenylated folate binding protein (80 µl), an FBP-folate complex is formed, the amount of which is dependent upon the analyte concentration in the sample.● 3rd incubation (9 min.): after the addition of streptavidin-coated microparticles (30 µl) and folate labeled with biotin (50 µl), the unbound sites of the Ruthenylated folate binding protein become occupied, with formation of a Ruthenylated folate binding protein-folate biotin complex. The entire complex becomes bound to the solid phase via interaction of biotin and streptavidin. |
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510(k) Summary, Continued
| 510(k) Summary, Continued | |
|---|---|
| BOEHRINGERMANNHEIMCORPORATION | Image: boehringer logo |
| 4) DeviceDescription,cont. | The reaction mixture is aspirated into the measuring cell where themicroparticles are magnetically captured onto the surface of the electrode.Unbound substances are then removed by washing with ProCell.Application of a voltage to the electrode then induces chemiluminescentemission which is measured by a photomultiplier (0.4 second read frame). Results are determined via a calibration curve which is instrument-specificgenerated by 2-point calibration and a master curve provided via thereagent bar code. |
| 5) Intended use | Assay for the in vitro quantitative determination of folate in human serum. |
| 6) Comparisonto predicatedevice | The Boehringer Mannheim Elecsys FOLATE is substantially equivalent toother products in commercial distribution intended for similar use. Mostnotably it is substantially equivalent to the currently marketed Bio-RadQuantaphase II® B12/FOLATE Radioassay (K935286).Studies performed include: evaluation of assay precision according to NCCLS recommendations determination of the lower detection limit demonstration of linearity correlation with the predicate device evaluation of the effect of various endogenous substances (biotin,triglyceride, lipemia, and rheumatoid factor), and commonly usedpharmaceutical compounds and serum sample comparisons, and stability studies. |
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Image /page/2/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes representing the agency's mission to protect the health of all Americans and provide essential human services. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Patricia M. Klimley Head, Elecsys Regulatory Program Boehringer Mannheim Corporation 4300 Hacienda Drive Pleasanton, California 94588-2722
NOV 1 2 1997
Re: K973674 Trade Name: Elecsys® FOLATE Regulatory Class: II Product Code: CDD Dated: September 24, 1997 Received: September 26, 1997
Dear Ms. Klimley:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General requlation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Requlations.
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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the requlation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Autman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known): Device Name: Elecsys® FOLATE Indications for Use:
Assay for the in vitro quantitative determination of folate in human serum. Fisody for are in The visual "ECLIA" is intended for use on the Boehringer Mannheim Elecsys assay analyzers.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. KC973674
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________
(Optional Format 1-2-96)
§ 862.1810 Vitamin B
12 test system.(a)
Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.(b)
Classification. Class II.