HEMAGEN ANTI CARDIOLIPIN SCREEN

{0} PAGE 1 K971039 510(k) Summary 1. Submitter's Name/Contact Person JUN - 3 1997 Joseph M. Califano, Regulatory Affairs Manager Address Hemagen Diagnostics, Inc. 34-40 Bear Hill Road Waltham, MA, 02154 Phone No: (617) 890-3766 Fax No: (617) 890-3748 e-mail: jcalifano@hemagen.com **Date Prepared** 7 March 1997 2. **Device Names** Trade Name: Hemagen ® aCL Screen Common Name: anti Cardiolipin screening assay Classification Name: Immunological test system, multiple autoantibodies {21 CFR 866.5660} 3. **Predicate Device(s)** a. Hemagen ® Anti-Cardiolipin IgG and IgM {EIA method} Reference 510 (k) Docket No. K 932373 b. Hemagen ® Anti-Cardiolipin IgA Calibrator Reagents {EIA method} Reference 510 (k) Docket No. K 941840 510(k) Summary - Page 1 {1} PAGE 2 ## 4 Description of Device 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 (μ), 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 IgG, IgM, and IgA autoantibodies to cardiolipin in human serum. ## 6. Performance Data ### I. Trivalent HRP Conjugate 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 %. 510(k) Summary - Page 2 {2} PAGE 3 # III. Comparison Testing 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 | | | NEG | 0 | 0 | | | TOTAL | 38 | 0 | | | 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 | | | NEG | 0 | 72 | | | TOTAL | 1 | 78 | | | 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 | | | NEG | 0 | 72 | | | TOTAL | 39 | 78 | | | 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 % | | | 510(k) Summary - Page 3 {3} PAGE 4 # 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. 510(k) Summary - Page 4 {4} DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Food and Drug Administration 2098 Gaither Road Rockville MD 20850 Mr. Joseph M. Califano Manager, Regulatory Affairs Hemagen Diagnostics, Inc. 34-40 Bear Hill Road Waltham, Massachusetts 02154 Re: K971039 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 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. 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. {5} Page 2 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 I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health Enclosure {6} COPY Device Name: Hemagen ® anti Cardiolipin Screen Indication(s) For Use 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 aCI 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) (Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number Prescription Use ☑ (Per 21 CFR 801.109) OR Over-The-Counter-Use