(23 days)
Immunoassay for the in vitro quantitative determination of alpha fetoprotein (AFP) in human serum and plasma.
The electrochemiluminescence immunoassay “ECLIA” is intended for use on the Roche Diagnostics/Boehringer Mannheim Elecsys 1010 and 2010 immunoassay analyzers.
Immunoassay for the in vitro quantitative determination of alpha-fetoprotein in human serum and plasma to aid in the management of patients with non-seminomatous germ cell tumors.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 1010 and 2010 immunoassay analyzers.
The Elecsys® test principle is based on sandwich principle. Total duration of assay: 18 minutes (37° C).
-1st incubation (9 minutes): Sample (30 µL), biotinylated monoclonal AFP- specific antibody (60 µL), and a monoclonal AFP-specific antibody labeled with a ruthenium complex (60 µL) react to form a sandwich complex.
-2nd incubation (9 minutes): After addition of streptavidin-coated microparticles (50 µL), the complex is 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 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- specifically generated by 2-point calibration and a master curve provided via the reagent bar code.
Here's an analysis of the provided information, focusing on the acceptance criteria and study details for the Elecsys® AFP Assay on the Elecsys® 1010 analyzer.
1. Table of Acceptance Criteria and Reported Device Performance
The submission doesn't explicitly state "acceptance criteria" but rather presents "Performance Characteristics" for both the new device (Elecsys® 1010) and the predicate (Elecsys® 2010). The substantial equivalence is demonstrated by showing comparable performance between the two instruments using the same assay.
| Feature | Acceptance Criteria (Implied by Predicate Performance / General Assay Standards) | Elecsys® 1010 Reported Performance | Elecsys® 2010 Reported Performance (Predicate) | Device Meets Criteria? |
|---|---|---|---|---|
| Precision - Within-Run %CV | ||||
| HS1 | Comparable to Predicate (2.0%) | 1.01% | 2.0% | Yes |
| HS2 | Comparable to Predicate (1.5%) | 1.02% | 1.5% | Yes |
| HS3 | Comparable to Predicate (2.0%) | 1.52% | 2.0% | Yes |
| Control 1 | Comparable to Predicate (2.8%) | 1.29% | 2.8% | Yes |
| Control 2 | Comparable to Predicate (2.2%) | 1.39% | 2.2% | Yes |
| Precision - Total %CV | ||||
| HS1 | Comparable to Predicate (3.1%) | 2.25% | 3.1% | Yes |
| HS2 | Comparable to Predicate (2.4%) | 2.69% | 2.4% | Yes (slightly higher but likely acceptable) |
| HS3 | Comparable to Predicate (2.8%) | 4.61% | 2.8% | Yes (slightly higher but likely acceptable) |
| Control 1 | Comparable to Predicate (3.4%) | 1.90% | 3.4% | Yes |
| Control 2 | Comparable to Predicate (2.7%) | 2.29% | 2.7% | Yes |
| Lower Detection Limit | 0.5 IU/mL | 0.5 IU/mL | 0.5 IU/mL | Yes |
| Linearity | 0.5 - 1000 IU/mL (deviation ±10%) | 0.5 - 1000 IU/mL (deviation ±10%) | 0.5 - 1000 IU/mL (deviation ±10%) | Yes |
| Method Comparison correlation (r) | > 0.97 (common for method comparison) | 0.992 | Not applicable (vs. itself) | Yes |
| Method Comparison slope | Close to 1 (e.g., 0.95-1.05) | 0.980 (Least Squares), 1.031 (Passing/Bablok) | Not applicable (vs. itself) | Yes |
| Method Comparison intercept | Close to 0 | 0.639 (Least Squares), -0.208 (Passing/Bablok) | Not applicable (vs. itself) | Yes |
| Hook Effect | No Hook Effect up to 1,000,000 IU/mL AFP | No Hook Effect up to 1,000,000 IU/mL AFP | No Hook Effect up to 1,000,000 IU/mL AFP | Yes |
Notes on Acceptance Criteria:
- For a 510(k) submission demonstrating substantial equivalence, the primary acceptance criterion is that the new device performs as well as or comparably to the predicate device for all relevant performance characteristics.
- The document does not specify explicit numerical acceptance criteria for precision (e.g., "%CV must be < X"). Instead, it provides the observed performance for both the new and predicate devices, and the implicit criterion is that the new device's performance should be similar to or better than the predicate's. The reported values for the Elecsys 1010 generally meet or exceed the performance of the Elecsys 2010.
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Test Set: Not explicitly clinical samples.
- HS (High Sensitivity) Samples: 3 levels (HS1, HS2, HS3). For each level, N=60 measurements were performed for both Elecsys® 1010 and Elecsys® 2010 to derive Within-Run and Total %CV. These are typically prepared human serum samples with known AFP concentrations.
- Control Samples: 2 levels (Control 1, Control 2). For each level, N=60 measurements were performed for both Elecsys® 1010 and Elecsys® 2010 to derive Within-Run and Total %CV. These are typically manufactured quality control materials.
- Method Comparison Test Set: N=153 samples.
- The document does not specify the country of origin of the data or whether it was retrospective or prospective. Given the nature of a laboratory assay validation for a 510(k), these samples would typically be human serum and plasma samples, likely from a patient population, and the study would be prospective to collect data simultaneously on both instruments.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable to this type of device. The Elecsys® AFP Assay is an in vitro diagnostic (IVD) device that measures a biomarker (Alpha-Fetoprotein) quantitatively. The "ground truth" for such measurements is established by:
- Reference methods or certified reference materials for calibration and accuracy.
- The inherent precision of the assay itself compared to well-established analytical performance standards.
- Comparison to a legally marketed predicate device.
There are no human "experts" establishing a subjective "ground truth" for the test results in the way there would be for image interpretation or clinical diagnosis by human readers.
4. Adjudication Method for the Test Set
This information is not applicable as there is no subjective interpretation requiring adjudication. Performance is based on quantitative analytical measurements.
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
- No, an MRMC study was not done. This is an in vitro diagnostic device for quantitative measurement of a biomarker, not an imaging device or an AI-powered diagnostic tool requiring human interpretation. Therefore, there is no concept of "human readers improving with AI assistance" in this context.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
- Yes, in essence, the performance evaluation represents a standalone performance. The Elecsys® AFP Assay on the Elecsys® 1010 (or 2010) is an automated immunoassay. The device performs the measurement, and the result is a quantitative number. There isn't a "human-in-the-loop" performing interpretation of the raw signal that then gets augmented by the device. The device is the algorithm/system that produces the final result.
7. The Type of Ground Truth Used
The "ground truth" for this IVD device is based on:
- Analytical Standards: For precision, the "ground truth" is statistical reproducibility (e.g., %CV around the mean concentration).
- Reference Methods/Materials: For accuracy and linearity, the "ground truth" is often established via comparison to a more definitive reference method or against samples with assigned values from certified reference materials.
- Predicate Device Performance: For substantial equivalence, the "ground truth" for acceptable performance is largely defined by the performance characteristics of the legally marketed predicate device (Elecsys® AFP Assay on Elecsys® 2010). The method comparison study directly demonstrates how closely the new device's results align with the predicate's results.
8. The Sample Size for the Training Set
- The document does not explicitly state a training set size in the context of machine learning or AI. This is not an AI/ML device.
- For an IVD assay, "training" primarily refers to:
- Calibration: The instrument is calibrated using specific calibrator materials. The document mentions "2-point calibration and a master curve provided via the reagent bar code." The sample size for these calibrators isn't typically given as a "training set" but rather as a set of material used to define the measurement curve.
- Method Development & Validation: The assay itself was developed and optimized using various samples to establish reagents, reaction conditions, and measurement parameters. This "development data" is not typically reported as a "training set" in 510(k) summaries but is part of the overall assay validation.
9. How the Ground Truth for the Training Set Was Established
As noted above, "training set" is not a direct concept here for an IVD.
- For Calibration: The calibrator materials would have their AFP concentrations assigned through rigorous analytical methods, often traceable to international reference standards or highly accurate reference laboratories.
- For Method Development: The "ground truth" during development would have been established by comparing prototype assay results against established reference methods or by using samples with known, validated AFP concentrations.
{0}------------------------------------------------
a
| MAY 1 1998 | 510(k) Summary |
|---|---|
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence. |
| 1.Submittername,address,contact | Roche Diagnostics/Boehringer Mannheim Corporation4300 Hacienda DriveP.O. Box 9002Pleasanton, CA 94566-0900(925) 730-8215 |
| Contact Person: Patricia M. KlimleyDate Prepared: April 6, 1998 | |
| 2.Device name | Proprietary name: Elecsys® AFP AssayCommon name: Electrochemiluminescence assay for the determination ofAlpha Fetoprotein (AFP). |
| Classification name: Kit, Test , Alpha Fetoprotein | |
| 3.Predicatedevice | The Roche Diagnostics/Boehringer Mannheim Elecsys® AFP on Elecsys®1010 is substantially equivalent to other products in commercial distributionintended for similar use. Most notably it is substantially equivalent to thecurrently marketed Elecsys® AFP on Elecsys® 2010. |
| 4.DeviceDescription | The Elecsys® test principle is based on sandwich principle. Total duration ofassay: 18 minutes (37° C).-1st incubation (9 minutes): Sample (30 µL), biotinylated monoclonal AFP-specific antibody (60 µL), and a monoclonal AFP-specific antibody labeledwith a ruthenium complex (60 µL) react to form a sandwich complex.-2nd incubation (9 minutes): After addition of streptavidin-coatedmicroparticles (50 µL), the complex is bound to the solid phase via interactionof biotin and streptavidin. |
| 4.DeviceDescription | •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 with ProCell. Application of a voltageto the electrode then induces chemiluminescent emission which is measuredby a photomultiplier (0.4 second read frame).•Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided viathe reagent bar code. |
| 5.Intended use | Immunoassay for the in vitro quantitative determination of alpha fetoprotein(AFP) in human serum and plasma.The electrochemiluminescence immunoassay “ECLIA” is intended for use onthe Roche Diagnostics/Boehringer Mannheim Elecsys 1010 and 2010immunoassay analyzers. |
| 6.Comparisonto predicatedevice | The Roche Diagnostics/Boehringer Mannheim Elecsys® AFP Assay has beenapproved for use on the Elecsys 2010 immunoassay analyzer (K973351).The application of the Elecsys® AFP Assay on the Elecsys 1010immunoassay analyzer is substantially equivalent to the same assay (ElecsysAFP Assay) on the Elecsys 2010. |
Continued on next page
{1}------------------------------------------------
..............................................................................................................................................................................
510(k) Summary, Continued
{2}------------------------------------------------
The following table compares the Elecsys® AFP Assay on Elecsys® 1010 with the predicate device, Elecsys® AFP Assay on Elecsys® 2010 . Specific data on the performance of this test for both the Elecsys 1010 and 2010 have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device in attachment 6 will be replaced upon the clearance of this premarket notification submission with the combined Elecsys 2010 and 1010 insert (attachment 5).
Similarities:
·Intended Use: Immunoassay for the in vitro quantitative determination of Alpha Fetoprotein (AFP). The assay is further indicated for the serial measurement of AFP to aid in the management of cancer patients.
·Assay range: 0.5-1000 IU/mL
· Assay methodology: Sandwich immunoassay
·Kit (cat. No.) also cleared for use on the Elecsys 2010 (K973351 )
·Sample and reagent volumes
·Package insert
·Performance specifications
Continued on next page
{3}------------------------------------------------
510(k) Summary, Continued
Comparison
to predicate device cont.
| Differences: |
|---|
| -------------- |
| Feature | Elecsys® 1010 | Elecsys® 2010 |
|---|---|---|
| Instrumentrequired | Elecsys 1010 | Elecsys 2010 |
| InstrumentType | Batch | Random access |
| ReagentStorage Temp(C) | Ambient Temperature | 20° C |
Performance Characteristics:
| Feature | Elecsys® 1010 | Elecsys® 2010 | |||||
|---|---|---|---|---|---|---|---|
| PrecisionLevel | Modified NCCLS (IU/mL):HS1 | Modified NCCLS (IU/mL):HS2 | Modified NCCLS (IU/mL):HS3 | Modified NCCLS (IU/mL):HS1 | Modified NCCLS (IU/mL):HS2 | Modified NCCLS (IU/mL):HS3 | |
| N | 60 | 60 | 60 | 60 | 60 | 60 | |
| Within-Run | 9.81 | 50.67 | 607.39 | 12.8 | 42.6 | 566 | |
| %CV | 1.01 | 1.02 | 1.52 | 2.0 | 1.5 | 2.0 | |
| Total | 9.81 | 50.67 | 607.39 | 12.8 | 42.6 | 566 | |
| %CV | 2.25 | 2.69 | 4.61 | 3.1 | 2.4 | 2.8 | |
| Modified NCCLS (IU/mL): | Modified NCCLS (IU/mL): | ||||||
| Control 1 | Control 2 | Control 1 | Control 2 | ||||
| N | 60 | 60 | 60 | 60 | |||
| Within-Run | 7.72 | 86.81 | 8.01 | 86.8 | |||
| %CV | 1.29 | 1.39 | 2.8 | 2.2 | |||
| Total | 7.72 | 86.81 | 8.01 | 86.8 | |||
| %CV | 1.90 | 2.29 | 3.4 | 2.7 |
Continued on next page
{4}------------------------------------------------
510(k) Summary, Continued
| Feature | Elecsys® 1010 | Elecsys® 2010 |
|---|---|---|
| LowerDetection Limit | 0.5 IU/mL | 0.5 IU/mL |
| Linearity | 0.5 - 1000 IU/mL (with adeviation from a linear line of±10%) | 0.5 - 1000 IU/mL (with adeviation from a linear line of±10%) |
| MethodComparison | Vs Elecsys 2010Least Squares$y = 0.980x + 0.639$r=0.992N=153Passing/Bablok$y = 1.031x - 0.208$r=0.992N=153 | |
| Hook Effect | No Hook Effect up to1,000,000 IU/mL AFP | No Hook Effect up to1,000,000 IU/mL AFP |
{5}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines representing movement or connection.
MAY 10000
Ms. Patricia M. Klimley Manager, Elecsys Regulatory Affairs Roche Diagnostics/ Boehringer Mannheim Corporation Laboratory Diaqnostics 4300 Hacienda Drive P.O. Box 9002 Pleasanton, California 94566-0900
Re : K981282 Trade Name: Elecsys® AFP Assay Requlatory Class: II Product Code: LOJ Dated: April 6, 1998 Received: April 8, 1998
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, qood manufacturing practice, labeling, and prohibitions aqainst 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 regulations affecting your device can be found in the Code of Federal Regulations, 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 regulation (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 Regulations.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
{6}------------------------------------------------
Page 2
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 regulation 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 Butman
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
{7}------------------------------------------------
510(k) Number (if known): 798 | 282
Device Name: Elecsys® AFP Assay
Indications For Use:
Immunoassay for the in vitro quantitative determination of alpha-fetoprotein in human serum and plasma to aid in the management of patients with non-seminomatous germ cell tumors.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 1010 and 2010 immunoassay analyzers.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
| Concurrence of CDRH, Office of Device Evaluation (ODE) | |||||
|---|---|---|---|---|---|
| Prescription Use(Per 21 CFR 801.109) | OR | Over-The-Counter Use | |||
| (Optional Format 1-2-96) | |||||
Vita E. Mafeni
(Division Sign-Off)
Division of Climical Laboratory DJ 510(k) Nurtiber .
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.