(74 days)
Not Found
No
The device description details a standard ELISA methodology for antibody detection, which relies on chemical reactions and optical density measurements, not AI/ML algorithms. The summary explicitly states "Mentions AI, DNN, or ML: Not Found".
No
This device is an in vitro diagnostic (IVD) device used to detect autoantibodies to cardiolipin in patient serum, aiding in the diagnosis of antiphospholipid syndrome. It does not treat or cure a disease, which would make it a therapeutic device.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay "is intended to be utilized as an aid in the diagnosis of antiphospholipid syndrome." This indicates its role in identifying or confirming a medical condition, which is the definition of a diagnostic device.
No
The device description clearly outlines a laboratory assay using ELISA methodology, involving physical reagents, microplates, and an ELISA plate reader, which are hardware components.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device is for "screening of patient serum for the presence of IgG, IgM, and IgA autoantibodies to cardiolipin" and is "intended to be utilized as an aid in the diagnosis of antiphospholipid syndrome." This clearly indicates that the device is used to examine specimens derived from the human body (serum) to provide information for diagnostic purposes.
- Device Description: The description details an ELISA methodology that analyzes components within patient serum (anticardiolipin antibodies). This process is performed in vitro (outside the body).
- Performance Studies: The performance studies involve testing "serum specimens from both disease state and normal patient panels," further confirming the use of human biological samples for diagnostic evaluation.
All of these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The device is intended for the qualitative detection of IqG. IgM, and IgA autoantibodies to cardiolipin in human serum.
The anti Cardiolipin Screen is indicated for the screening of patient serum for the presence of IgG, IgM, and IgA autoantibodies to cardiolipin . Autoantibodies to aCl are typically observed in patients with systemic lupus erythematosus and other connective tissue diseases. This assay is intended to be utilized as an aid in the diagnosis of antiphospholipid syndrome.
Product codes
MID
Device Description
The ELISA methodology is commonly used for serum antibody evaluations. In this assay, purified bovine cardiolipin has been attached to the inner surfaces of microplate test wells by the manufacturer. The user adds diluted patient samples to the wells. Anticardiolipin antibodies in patient serum bind specifically to the cardiolipin antigen attached to the plate, and remain in place after a wash step.
A trivalent second antibody cocktail, consisting of peroxidase-conjugated goat anti-human IgG (Fc), IgM (u), and IgA (α), is added to the wells. After an incubation/wash step, TMB (tetramethylbenzidine) substrate is added. In the wells containing bound cardiolipin-anticardiolipin complexes, the peroxidase enzyme catalyzes a color change in the TMB substrate. After the reaction is stopped with dilute sulfuric acid, the color is read in an ELISA plate reader. Optical densities (ODs) of patient samples are compared to the OD of a reference serum included in the kit.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
117 serum specimens from both disease state and normal patient panels were screened concurrently with both the proposed and predicate devices. Receiver Operating Characteristic {ROC}techniques were used to derive an optimized cutoff OD to be utilized in the preparation of the Cutoff Serum.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
I. Trivalent HRP Coniugate Standardization
IgG, IgM, and IgA standard preparations (Louisville APL Diagnostics, Inc.) were diluted in Serum Diluent and tested with the predicate devices to establish standard curves. Optimal second antibody concentrations were established by titration for each monovalent HRP conjugate. The three conjugates were then blended, verified against the standard calibration curves, and freeze-dried.
II. Cutoff Serum Standardization
117 serum specimens from both disease state and normal patient panels were screened concurrently with both the proposed and predicate devices. Receiver Operating Characteristic {ROC}techniques were used to derive an optimized cutoff OD to be utilized in the preparation of the Cutoff Serum. Based upon this analysis and comparison testing, the optimized cutoff OD has demonstrated a relative analytical sensitivity of ≥ 97.0 %
III. Comparison Testing
A total of 117 samples were evaluated using the Hemagen ® antiCardiolipin Screen , the Hemagen ® Anti-Cardiolipin IgG/ IgM assays, and the Hemagen ® Anti-Cardiolipin IgA Calibrator Reagents.
Table 1: Positive Panel, N = 38
Relative analytical sensitivity = 100% {38/38}, 0.95 INTERVAL 90.8% to 100%
Table 2: Normal Panels, N=79
The relative analytical specificity 92.3 % {72/78}, 0.95 INTERVAL 84.2% to 96.4 %
Table 3: Combined Panels, N = 117
Relative sensitivity = 100 % {39/39} , 0.95 INTERVAL 91.0 % to 100 %
Relative specificity 92.3 % {72/78} , 0.95 INTERVAL 84.2 % to 96.4 %
IV. A. Precision
To evaluate anti Cardiolipin Screen precision, inter-assay and intra-assay studies were conducted.
-
Inter-assay precision: Three serum samples (negative, low positive, high positive), the Cutoff Serum, and the Positive Control were assayed five times each, twice a day, on five different days.
- Negative: Mean OD 0.059, Std. Dev. 0.007, CV 12.3 %
- Low Positive: Mean OD 0.197, Std. Dev. 0.023, CV 11.7 %
- High Positive: Mean OD 0.967, Std. Dev. 0.067, CV 6.9 %
- Cutoff Serum: Mean OD 0.115, Std. Dev. 0.015, CV 13.0 %
- Positive Control: Mean OD 0.697, Std. Dev. 0.074, CV 10.7 %
-
Intra-assay precision: Three serum samples (negative, low positive, high positive) were assayed 16 consecutive times in a single run.
- Negative: Mean OD 0.069, Std. Dev. 0.010, CV 15.0 %
- Low Positive: Mean OD 0.306, Std. Dev. 0.022, CV 7.1 %
- High Positive: Mean OD 1.112, Std. Dev. 0.072, CV 6.5 %
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Relative analytical sensitivity = 100% {38/38}
Relative analytical specificity 92.3 % {72/78}
Relative sensitivity = 100 % {39/39}
Relative specificity 92.3 % {72/78}
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).
0
PAGE
1
510(k) Summary
Submitter's Name/Contact Person
JUN - 3 1997
Joseph M. Califano, Regulatory Affairs Manager
Address
1
Hemagen Diagnostics, Inc. 34-40 Bear Hill Road Waltham, MA, 02154 (617) 890-3766 Phone No: (617) 890-3748 Fax No: jcalifano@hemagen.com e-mail:
Date Prepared
7 March 1997
2 Device Names
Trade Name: Hemagen ® aCL Screen anti Cardiolipin screening assay Common Name: Immunological test system, multiple Classification Name: autoantibodies {21 CFR 866.5660}
3 Predicate Device(s)
- Hemagen ® Anti-Cardiolipin IgG and IgM {EIA method} a. Reference 510 (k) Docket No. K 932373
- Hemagen ® Anti-Cardiolipin IgA Calibrator Reagents {EIA method} b. Reference 510 (k) Docket No. K 941840
510(k) Summary - Page 1
1
Description of Device 4
The ELISA methodology is commonly used for serum antibody evaluations. In this assay, purified bovine cardiolipin has been attached to the inner surfaces of microplate test wells by the manufacturer. The user adds diluted patient samples to the wells. Anticardiolipin antibodies in patient serum bind specifically to the cardiolipin antigen attached to the plate, and remain in place after a wash step.
A trivalent second antibody cocktail, consisting of peroxidase-conjugated goat anti-human IgG (Fc), IgM (u), and IgA (α), is added to the wells. After an incubation/wash step, TMB (tetramethylbenzidine) substrate is added. In the wells containing bound cardiolipin-anticardiolipin complexes, the peroxidase enzyme catalyzes a color change in the TMB substrate. After the reaction is stopped with dilute sulfuric acid, the color is read in an ELISA plate reader. Optical densities (ODs) of patient samples are compared to the OD of a reference serum included in the kit.
5 Intended Use of Device
The device is intended for the qualitative detection of IqG. IgM, and IgA autoantibodies to cardiolipin in human serum.
Performance Data ర్.
1. Trivalent HRP Coniugate Standardization
IgG, IgM, and IgA standard preparations (Louisville APL Diagnostics, Inc.) were diluted in Serum Diluent and tested with the predicate devices to establish standard curves. Optimal second antibody concentrations were established by titration for each monovalent HRP conjugate. The three conjugates were then blended, verified against the standard calibration curves, and freeze-dried.
II. Cutoff Serum Standardization
117 serum specimens from both disease state and normal patient panels were screened concurrently with both the proposed and predicate devices. Receiver Operating Characteristic {ROC}techniques were used to derive an optimized cutoff OD to be utilized in the preparation of the Cutoff Serum. Based upon this analysis and comparison testing, the optimized cutoff OD has demonstrated a relative analytical sensitivity of ≥ 97.0 %
2
III. Comparison Testing
TOTAL
39
The Hemagen ® antiCardiolipin Screen , the Hemagen ® Anti-Cardiolipin IgG/ IgM assays, and the Hemagen ® Anti-Cardiolipin IgA Calibrator Reagents were used to concurrently assay serum specimens from patients positive for aCl, and from normal blood donors. A total of 117 samples were evaluated.
| Table 1: Positive Panel, N = 38 | ||||
|---|---|---|---|---|
| Predicate Devices | ||||
| POS | NEG | TOTAL | ||
| Proposed | ||||
| Device | POS | 38 | 0 | 38 |
| NEG | 0 | 0 | 0 | |
| TOTAL | 38 | 0 | 38 | |
| Relative analytical sensitivity = 100% {38/38}, 0.95 INTERVAL 90.8% to 100% | ||||
| Table 2: Normal Panels, N=79 | ||||
| Predicate Devices | ||||
| POS | NEG | TOTAL | ||
| Proposed | ||||
| Device | POS | 1 | 6 | 7 |
| NEG | 0 | 72 | 72 | |
| TOTAL | 1 | 78 | 79 | |
| The indeterminate samples were retested with the proposed device. | ||||
| The relative analytical specificity 92.3 % {72/78}, 0.95 INTERVAL 84.2% to 96.4 % | ||||
| Table 3: Combined Panels, N = 117 | ||||
| Predicate Devices | ||||
| POS | NEG | TOTAL | ||
| Proposed | ||||
| Device | POS | 39 | 6 | 45 |
| NEG | 0 | 72 | 72 |
Relative sensitivity = 100 % {39/39} , 0.95 INTERVAL 91.0 % to 100 % Relative specificity 92.3 % {72/78} , 0.95 "NTERVAL 84.2 % to 96.4 %
117
78
510(k) Summary - Page 3
3
IV. A. Precision
To evaluate anti Cardiolipin Screen precision, inter-assay and intra-assay studies were conducted.
Inter-assay precision
Three serum samples with various levels of anticardiolipin (negative, low positive, and high positive), the Cutoff Serum, and the Positive Control were assayed five times each, twice a day, on five different days:
| Sample | Mean OD | Std. Dev. | CV |
|---|---|---|---|
| Negative | 0.059 | 0.007 | 12.3 % |
| Low Positive | 0.197 | 0.023 | 11.7 % |
| High Positive | 0.967 | 0.067 | 6.9 % |
| Cutoff Serum | 0.115 | 0.015 | 13.0 % |
| Positive Control | 0.697 | 0.074 | 10.7 % |
Intra-assay precision
Three serum samples with various levels of anticardiolipin (negative, low positive, and high positive) were assayed 16 consecutive times in a single run:
| Sample | Mean OD | Std. Dev. | CV |
|---|---|---|---|
| Negative | 0.069 | 0.010 | 15.0 % |
| Low Positive | 0.306 | 0.022 | 7.1 % |
| High Positive | 1.112 | 0.072 | 6.5 % |
Conclusions
The results of the comparative studies support the claim that the Hemagen ® anti Cardiolipin Screen is substantially equivalent to the comparative devices, and performs as an effective screening assay for the detection of autoantibodies to anticardiolipin IgA, IgG, and IgM in human serum.
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Image /page/4/Picture/1 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 forming its wing and tail. The eagle is positioned within a circular border that contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA".
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUN - 3 1997
Mr. Joseph M. Califano Manager, Regulatory Affairs Hemagen Diagnostics, Inc. 34-40 Bear Hill Road ---Waltham, Massachusetts 02154
K971039 Re: Trade Name: Hemagen® aCL Screen Regulatory Class: II Product Code: MID Dated: March 20, 1997 Received: March 21, 1997
Dear Mr. Califano:
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 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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP 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 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.
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.
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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 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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Indication(s) For Use
18 11 11 11 11
- 1
The anti Cardiolipin Screen is indicated for the screening of patient serum for the presence of IgG, IgM, and IgA autoantibodies to cardiolipin . Autoantibodies to aCl are typically observed in patients with systemic lupus erythematosus and other connective tissue diseases. This assay is intended to be utilized as an aid in the diagnosis of antiphospholipid syndrome.
(PLEASE DO NOT WRITE BELOW THIS LINE)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Peter E. Massim
on of Di 51 Offe) Number
Prescription Use (Per 21 CFR 801.109)
OR
Over-The-Counter-Use