(61 days)
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No
The summary describes a standard turbidimetric immunoassay and clinical chemistry analyzer functionality. There is no mention of AI, ML, or related concepts in the device description, intended use, or performance studies. The analysis relies on a stored calibration curve and absorbance measurements, which are traditional methods.
No.
The device is an in vitro diagnostic (IVD) test intended to aid in the diagnosis of IgE-mediated allergic disorders by quantitatively determining Total Immunoglobulin E (IgE) concentration. It is used for diagnostic purposes and does not provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states, "The determination aids in the diagnosis of IgE-mediated allergic disorders in conjunction with other clinical findings."
No
The device is a reagent kit and calibrator set used with a clinical chemistry analyzer, which are physical components, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use Statement: The document explicitly states "For in vitro diagnostic use only." This is a clear indicator of the device's intended purpose.
- Function: The device is designed to quantitatively determine the concentration of Total Immunoglobulin E (IgE) in human serum and plasma. This analysis is performed in vitro (outside the living body) on biological samples.
- Clinical Purpose: The determination of IgE concentration aids in the diagnosis of IgE-mediated allergic disorders, which is a clinical application.
- Device Description: The description details a reagent kit and its use on clinical chemistry analyzers to measure an analyte in a biological sample using a turbidimetric immunoassay methodology. This is characteristic of an IVD.
- Performance Studies: The document describes various performance studies (Method Comparison, Precision, Analytical Range, Sensitivity, Specificity, Anticoagulant Studies, In-Use Stability) which are standard for validating the performance of an IVD.
- Predicate Device: The mention of a predicate device (K061970; Elecsys IgE II Immunoassay) indicates that this device is being compared to an existing, cleared IVD.
N/A
Intended Use / Indications for Use
The IgE assay is intended for use in the quantitative determination of Total Immunoglobulin E (IgE) concentration in human serum and plasma (lithium heparin, K2-EDTA, K3-EDTA, K3-EDTA) on Beckman Coulter AU/DxC AU clinical chemistry analyzers. The determination aids in the diagnosis of IgEmediated allergic disorders in conjunction with other clinical findings. For in vitro diagnostic use only.
Product codes (comma separated list FDA assigned to the subject device)
DGC
Device Description
The Total Immunoglobulin E (IgE) reagent kit is in a liquid ready-to-use format designed for optimal performance on Beckman Coulter's AU/DxC AU clinical chemistry analyzers. Each reagent kit contains one buffer reagent (R1), one antibody reagent (R2), and a six-level lot matched calibrator set. The IgE reagent test system utilizes a turbidimetric immunoassay methodology. The AU analyzer measures the change in absorbance at 800 nm to calculate and express the concentration of immunoglobulin E in the test sample based on a stored calibration curve. The IgE assay is traceable to the World Health Organization (WHO) 3rd International Standard 11/234.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Comparison testing: Comparative studies were conducted for the candidate IgE reagent test system on the DxC 700 AU Clinical Chemistry Analyzer. Equivalence was demonstrated through a method comparison study. Additional performance studies verified that the technological differences between the candidate and predicate devices did not adversely affect safety and effectiveness. Discussions of the following performance parameters are presented in this 510(k) Summary: Method Comparison, Imprecision, Linearity, Sensitivity, Reference Interval, Specificity, Anticoagulants, In-use (Reagent Onboard & Calibration) Stability.
Method Comparison Summary:
Study type: Method comparison and bias estimation experiments.
Sample size: 136 fresh serum samples.
Data source: Patient samples.
Protocol: CLSI Guideline EP09c "Measurement Procedure Comparison and Bias Estimation Using Patient Samples - Third Edition".
Key results: The study evaluated 136 fresh serum samples spanning the analytical measuring range of the candidate IgE assay, where test sample concentrations ranged from approximately 25 to 499 IU/mL IgE as measured by the predicate assay. Slope [95% C.I.]: 0.966 [0.950 - 0.981]. Intercept (IU/mL) [95% C.I.]: 1.0 [-1.0 - 3.0]. R: 0.996.
Precision:
Study type: Repeatability (within-run) and within-laboratory (total) precision studies.
Sample size: Not explicitly stated, but includes two levels of human serum-based quality control material and three patient pools. Experimental design used duplicate sample analysis twice daily over twenty working days (N=80).
Protocol: CLSI Guideline EP05-A3 "Evaluation of Quantitative Measurement Procedures; Approved Guideline - Third Edition".
Key results: All test samples (Control 1, Control 2, Pool 1, Pool 2, Pool 3) passed both repeatability and total precision criteria.
Analytical Range (Linearity):
Study type: Analytical range (linearity) studies.
Sample size: 15-level linearity test set.
Protocol: CLSI guideline EP06-A "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline".
Key results: The assay was deemed linear. Linear Range (IU/mL): 20 – 500. Linear From: 13.2. Linear To: 575.5. Weighted Linear Regression: y = 1.01273x + 0.630, R2 = 0.99990. All samples passed linearity criteria.
Sensitivity (Detection Capability):
Study type: Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) studies.
Sample size: Two lots of candidate IgE reagent.
Protocol: CLSI guideline EP17-A2 "Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures Approved Guideline - Second Edition" using the Classical Approach.
Key results: All lots passed LoB, LoD, and LoQ claims. LoB Result for Lot 1: 5.9; LoB Claim: ≤10.0. LoD Result for Lot 1: 13.8; LoD Claim: ≤15.0. LoQ Result for Lot 1: 19.6 at 11.9% CV; LoQ Claim: ≤20.0 at ≤35% CV. Similar results for Lot 2.
Analytical Specificity:
Study type: Interference studies.
Protocol: CLSI Guidelines EP07 "Interference Testing in Clinical Chemistry - Third Edition" and EP37 "Supplemental Tables for Interference Testing in Clinical Chemistry".
Key results: Hemoglobin, unconjugated Bilirubin, Lipemia, RF, and 21 common drugs and concentrations showed No Significant Interference (NSI). Antibody specificity studies showed no cross-reactivity with human IgA, IgD, IgG, or IgM. Omalizumab is a known interferent and was not tested.
Anticoagulant Studies (Serum vs. Plasma):
Study type: Methods comparison studies (plasma as equivalent sample type).
Sample size: 55 samples for Na Heparin, Li Heparin, K2 EDTA; 53 samples for K3 EDTA.
Protocol: CLSI Guideline EP09c "Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Third Edition".
Key results: All plasma types (Na Heparin, Li Heparin, K2 EDTA, K3 EDTA) passed the acceptance criteria for Slope, Intercept, and R, demonstrating equivalency.
In-Use Stability:
Study type: In-Use Stability studies.
Protocol: CLSI EP25-A guideline "Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline".
Key results: Reagent open bottle, calibration interval, and calibrator open bottle stability claims passed for 29 months shelf life and tested beyond claimed days.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Linear Range (IgE): 20 - 500 IU/mL
Limit of Detection (IgE): 15 IU/mL
Limit of Quantitation (IgE): 20 IU/mL with ≤ 35% CV
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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§ 866.5510 Immunoglobulins A, G, M, D, and E immunological test system.
(a)
Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.(b)
Classification. Class II (performance standards).
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
March 23, 2022
Beckman Coulter, Inc. Veronica Colinayo Staff Regulatory Affairs 250 S. Kraemer Boulevard, Mail Stop B1.SE.03 Brea, California 92821
Re: K220178
Trade/Device Name: Total Immunoglobulin E (IgE) Regulation Number: 21 CFR 866.5510 Regulation Name: Immunoglobulins A, G, M, D, And E Immunological Test System Regulatory Class: Class II Product Code: DGC Dated: January 20, 2022 Received: January 21, 2022
Dear Veronica Colinayo:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
1
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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ying Mao. Ph.D. Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
Submission Number (if known)
Device Name
Total Immunoglobulin E (IgE)
Indications for Use (Describe)
The IgE assay is intended for use in the quantitative determination of Total Immunoglobulin E (lgE) concentration in human serum and plasma (lithium heparin, K2-EDTA, K3-EDTA, K3-EDTA) on Beckman Coulter AU/DxC AU clinical chemistry analyzers. The determination aids in the diagnosis of IgEmediated allergic disorders in conjunction with other clinical findings. For in vitro diagnostic use only.
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)
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Image /page/3/Picture/0 description: The image contains the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, resembling a stylized eye or a wave pattern. To the right of the oval is the company name, "BECKMAN COULTER," written in bold, black capital letters, with "BECKMAN" on the top line and "COULTER" on the bottom line.
1.0 Submitted By
Veronica V. Colinayo Staff Regulatory Affairs Beckman Coulter, Inc. 250 S. Kraemer Blvd. Mail Stop: B1.SE.03 Brea, CA 92821 Telephone: (714) 961-6515 Fax: (714) 961-4234 Email: vvcolinayo@beckman.com
2.0 Date Submitted
January 20, 2022
3.0 Device Name(s)
3.1 Proprietary Names
Total Immunoglobulin E (IgE)
3.2 Classification Name
Immunoglobulins A, G, M, D, and E immunological test system [866.5510, Product Code DGC]
4.0 Predicate Device
| Candidate Device | Predicate Device | Manufacturer | Docket
Number |
|---------------------------------|-------------------------------|-------------------|------------------|
| Total Immunoglobulin E
(IgE) | Elecsys IgE II
Immunoassay | Roche Diagnostics | K061970 |
5.0 Device Description
The Total Immunoglobulin E (IgE) reagent kit is in a liquid ready-to-use format designed for optimal performance on Beckman Coulter's AU/DxC AU clinical chemistry analyzers. Each reagent kit contains one buffer reagent (R1), one antibody reagent (R2), and a six-level lot matched calibrator set. The IgE reagent test system utilizes a turbidimetric immunoassay methodology. The AU analyzer measures the change in absorbance at 800 nm to calculate and express the concentration of immunoglobulin E in the test sample based on a stored calibration curve. The IgE assay is traceable to the World Health Organization (WHO) 3rd International Standard 11/234.
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6.0 Intended Use
The IgE assay is intended for use in the quantitative determination of Total Immunoglobulin E (IgE) concentration in human serum and plasma (lithium heparin, sodium heparin, K2 EDTA, K3 EDTA) on Beckman Coulter AU/DxC AU clinical chemistry analyzers. The determination aids in the diagnosis of IgE-mediated allergic disorders in conjunction with other clinical findings. For in vitro diagnostic use only.
7.0 Comparison to the Predicate
The following table describes the similarities and differences between the candidate device and the predicate device identified in Section 4.0 of this summary:
| Device | Similarities | |
|---|---|---|
| Intended Use: quantitative determination of total IgE for IVD use | ||
| Sample types: serum, plasma (heparin & EDTA) | ||
| Format: liquid, ready-to-use | ||
| Antibody: monoclonal, mouse | ||
| Storage conditions: 2-8°C | Same as Roche's | |
| IgE II assay on the Cobas Immunoassay System | ||
| Differences | ||
| Beckman | ||
| Coulter IgE | ||
| assay for | ||
| AU/DxC AU | ||
| Clinical | ||
| Chemistry | ||
| Analyzers | Operating Principle | |
| Assay Format | ||
| Calibrator scheme | ||
| Calibration Stability | IgE: 14 days | |
| IgE II: 7 days | ||
| Traceability | IgE: WHO 3rd IRP 11/234 | |
| IgE II: WHO 2nd IRP 75/502 | ||
| Analytical Measuring Range | IgE: 20 - 500 IU/mL | |
| IgE II: 0.100 - 2500 IU/mL | ||
| Extended Measuring Range | ||
| (manual or auto-dilution) | IgE: 500 - 1,000 IU/mL | |
| IgE II: >2,500 up to 50,000 IU/mL | ||
| Limit of Detection | IgE: 15 IU/mL | |
| IgE II: 0.100 IU/mL | ||
| Limit of Quantitation | IgE: 20 IU/mL with ≤ 35% CV | |
| IgE II: 0.500 IU/mL with 71.4 IU/mL; total precision criteria is 7.0 IU/mL for mean recovery values ≤ 93.3 IU/mL, and 7.5% CV for mean recovery values > 93.3 IU/mL. |
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9.3 Analytical Range (Linearity)
Analytical range (linearity) studies were designed in accordance with the CLSI guideline EP06-A "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline". The study used a 15-level linearity test set of inter-diluted patient pools that spanned the claimed analytical measuring range of the candidate IgE assay. The initial assessment of the study data in accordance with the EP06-A document found the modelled non-linearity to be not statistically significant, and the assay was deemed linear; as such, no further evaluation of non-linear models against a bias criterion was required. Table 9.3.1 provides the linearity study summary that supports the analytical measuring range claim for the candidate IgE assay, and Table 9.3.2 provides the linearity test results.
| Sample
Type | Acceptance Criterion | | Results | | Pass/
Fail |
|----------------------------|-------------------------|---------------------------------------|--------------------------------------|-----------|---------------|
| | Linear Range
(IU/mL) | Allowable Difference
Specification | Linear From | Linear To | |
| Serum | 20 – 500 | 10.0 IU/mL or 10.0%* | 13.2 | 575.5 | Pass |
| Weighted Linear Regression | | | y = 1.01273x + 0.630
R2 = 0.99990 | | |
Table 9.3.1 IgE Linearity Study Summary
*Values ≤100 IU/mL use the unit specification, and > 100 IU/mL use the percent specification.
| Sample | Target | Average | Predicted
Order 1 | Predicted
Nonlinear | COV | Bias | Bias
Spec | %Bias | %Bias
Spec | Pass/
Fail |
|--------|--------|---------|----------------------|------------------------|-------|------|--------------|-------|---------------|---------------|
| LIN_01 | 13.2 | 13.2 | 14.0 | N/A* | 100.0 | N/A* | 10.0 | N/A* | - | Pass |
| LIN_02 | 15.1 | 16.4 | 15.9 | N/A* | 100.0 | N/A* | 10.0 | N/A* | - | Pass |
| LIN_03 | 24.5 | 25.2 | 25.4 | N/A* | 100.0 | N/A* | 10.0 | N/A* | - | Pass |
| LIN_04 | 50.7 | 52.1 | 52.0 | N/A* | 100.0 | N/A* | 10.0 | N/A* | - | Pass |
| LIN_05 | 88.2 | 90.9 | 90.0 | N/A* | 100.0 | N/A* | 10.0 | N/A* | - | Pass |
| LIN_06 | 155.7 | 157.6 | 158.3 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
| LIN_07 | 215.6 | 220.0 | 219.0 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
| LIN_08 | 266.2 | 269.2 | 270.2 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
| LIN_09 | 331.8 | 335.3 | 336.7 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
| LIN_10 | 388.1 | 392.2 | 393.7 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
| LIN_11 | 425.6 | 428.7 | 431.6 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
| LIN_12 | 463 | 473.8 | 469.5 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
| LIN_13 | 511.8 | 520.9 | 518.9 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
| LIN_14 | 530.5 | 542.6 | 537.9 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
| LIN_15 | 575.5 | 575.5 | 583.5 | N/A* | 100.0 | N/A* | - | N/A* | 10.0 | Pass |
Table 9.3.2 IgE Linearity Study Degree of Non-Linearity Test Results
*Not Applicable: The non-linearity was deemed not statistically significant, therefore no additional bias assessment between the non-linear and linear models was required.
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9.4 Sensitivity (Detection Capability)
Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) studies were designed from the CLSI guideline EP17-A2 "Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures Approved Guideline - Second Edition" using the Classical Approach. The EP17 study evaluated two lots of candidate lgE reagent on one DxC 700 AU analyzer. The LoB evaluation assessed four unique lots of Immunoglobulin (Ig)-depleted human serum as the individual blank samples, and the LoD and LoQ evaluations used native patient pools diluted with Ig-depleted serum to achieve the low analyte levels. The results of the Detection Capability Study are shown in Table 9.4.1.
| Reagent Lot | LoB Result | LoB Claim | LoD Result | LoD Claim | LoQ Result | LoQ Claim | Pass/Fail |
|---|---|---|---|---|---|---|---|
| (IU/mL) | |||||||
| 1 | 5.9 | ≤10.0 | 13.8 | ≤15.0 | 19.6 at 11.9% CV | ≤20.0 at ≤35% CV | Pass |
| 2 | 7.5 | 12.5 | 17.8 at 7.8% CV | Pass |
| Table 9.4.1 IqE Detection Limit Study Summary (LoB, LoD & LoQ) | ||
|---|---|---|
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9.5 Reference Interval (Expected values)
IgE reference intervals are significantly influenced by age, sex, geographic location, microflora of the gastrointestinal tract, diet of the population, as well as environmental factors such as climate change.1 As such, Beckman Coulter recommends that each clinical laboratory establish a range of expected values for its own local population, as dictated by good laboratory practices. The reference intervals presented in Table 7.5.1 were taken from literature.2
| Analyte | Sample Type | Condition (age) | Levels (kIU/L)* |
|---|---|---|---|
| IgE | Serum | 0 - 100 IU/mL (sample containing no interferent). |
The interference study results are presented in Tables 9.6.1 and 9.6.2. The drug omalizumab is a known interferent with the IgE assay methodology1 and was not tested; falsely decreased results may occur in patients being treated with the drug. Antibody specificity studies were performed externally by the supplier of the monoclonal antibody component and showed no cross-reactivity with human IgA, IqD, IgG, or IgM.
| Substance | Sample Type | Source | Level Tested | Observed Effect |
|---|---|---|---|---|
| Hemoglobin | Serum | Hemolysate (human) | 1,000 mg/dL | NSI |
| Unconjugated Bilirubin | Serum | Porcine | 60 mg/dL | NSI |
| Lipemia | Serum | Intralipid | 1,000 mg/dL | NSI |
| RF | Serum | Human | 250 IU/mL | NSI |
Table 9.6.1 IgE Endogenous Interferents Study Summary
NSI = No Significant Interference within ± 10.0 IU/mL or 10%
| Substances | Sample Type | Analyte Level
(IU/mL) | Range of
Observed
Mean % Bias | Observed
Effect |
|------------------------------------------|-------------|--------------------------|-------------------------------------|--------------------|
| 21 common
drugs and
concentrations | Serum | ~160 | -1.6% to 0.9% | NSI |
NSI = No Significant Interference within ± 10.0 IU/mL or 10%
1 Hamilton RG. Accuracy of Food and Drug Administration-cleared IgE antibody assays in the presence of anti-IgE (omalizumab). J Allergy Clin Immunol. 2006;117(4):759-766
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9.7 Anticoagulant Studies (Serum vs. Plasma)
Methods comparison studies were used to evaluate plasma as an equivalent sample type. The methods comparison and bias estimation experiments were designed using the CLSI Guideline EP09c "Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Third Edition". The study utilized freshly drawn serum and plasma from apparently healthy adult volunteer donors, where five specimen tubes were drawn from each donor: one serum tube and one tube of each type of anticoagulant. The acceptance criteria and study results are summarized in Table 9.7.1 based on Weighted Deming regression analysis.
| Plasma
Type | Level
Tested | N | Slope
[0.9 - 1.1] | Intercept
[± 20 IU/mL] | R
[≥ 0.97] | Pass/
Fail |
|----------------|-----------------|----|----------------------|---------------------------|---------------|---------------|
| Na Heparin | 17 Units/mL | 55 | 0.989 | 0.0 | 0.999 | Pass |
| Li Heparin | 17 Units/mL | 55 | 0.989 | -0.5 | 0.999 | Pass |
| K2 EDTA | 1.8 mg/mL | 55 | 0.986 | -1.7 | 0.997 | Pass |
| K3 EDTA | 1.8 mg/mL | 53 | 0.964 | -2.4 | 0.998 | Pass |
Table 9.7.1 IgE Anticoagulant Study Results Summary
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9.8 In-Use Stability
In-Use Stability studies were designed to verify the open-bottle stability claims for the candidate IqE kit components and the IqE assay calibration interval. Testing was designed in accordance with the CLSI EP25-A guideline "Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline" using a classical design for sampling, storage, and testing. The study design evaluated in-use metrics at both the start and end of the shelf stability period for reagent kits stored under normal conditions (2-8°C) and including reagent kits that were exposed to post-shipping stress conditions. Three levels of quality control material were evaluated through the duration of the test period, where the mean lgE recovery at the last time point must be within 10 IU/mL or 10% of the mean Day 0 recovery. Table 9.8.1 summarizes the study results for the prestressed reagent kits beyond the claimed shelf life of 24 months.
| Pre-stress
Condition | Shelf Life
(months) | Stability Parameter
(2-8°C storage) | Claim
(days) | Tested to
(days) | Pass/Fail |
|-------------------------|------------------------|----------------------------------------|-----------------|---------------------|-----------|
| Winter
Summer | 29 | Reagent open bottle* | 28 | 29 | Pass |
| Winter
Summer | 29 | Calibration interval† | 14 | 15 | Pass |
| Winter
Summer | 29 | Calibrator open bottle | 45 | 54 | Pass |
Table 9.8.1: IqE In-Use Stability Study Summary
*Reagent stored onboard (on instrument) for study duration
*For Calibration Cycle 1, the Day 15 test point uses the Day 0 calibration curve; for Calibration Cycle 2, the Day 15 test point uses a new calibration curve based on a Day 15 recalibration.
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10.0 Conclusion
Beckman Coulter's Total Immunoglobulin E (IgE) Reagent is substantially equivalent to the Roche Elecsys IgE II reagent test system (K061970) as demonstrated through methods comparison and precision studies. The performance testing presented in this submission provides evidence that the device is safe and effective in its intended use.
This 510(k) Summary is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.