BAYER PSA ASSAY

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image shows the date "APR 13 2000" in a bold, sans-serif font. The letters and numbers are printed in black ink. The date is likely extracted from a document or photograph, and it represents April 13, 2000. Image /page/0/Picture/1 description: The image shows a handwritten string of characters, which appears to be a combination of letters and numbers. The string reads 'K994221'. The characters are written in a simple, slightly slanted style, with varying stroke thicknesses. The handwriting is clear and legible against the plain background. # Summary of Safety and Effectiveness As required by 21 CFR 807.92, the following 510(k) Summary is provided: #### 1. Submitter Information | Contact person: | William J. Pignato | |-----------------------------------------------------------|---------------------------------------------------------------------------------------------------------------| | Address:<br>63 North Street<br>Medfield, MA 02052 | Bayer Diagnostics Corporation | | Phone:<br>FAX:<br>e-mail: | (508) 359-3825<br>(508) 359-3356<br>william.pignato.b@bayer.com | | Date Summary Prepared: | April 5, 2000 | | Device Information | | | Proprietary Name:<br>Common Name:<br>Classification Name: | ADVIA: Centaur and ACS: 180 ePSA Assay<br>PSA Immunoassay<br>Reclassified to Class II, classification numbers | #### 3. Predicate Device Information | Name: | Immuno I PSA Immunoassay | |---------------|--------------------------| | Manufacturer: | Bayer Diagnostics | The Immuno 1 PSA Immunoassay was approved by FDA as PMA #P950021 and downclassified to class II by 21 CFR 866.6010, Tumor Associated AntigenImmunological Test System on Dec 17, 1997. unknown #### 4. Device Description 2. PSA is detected in the serum of males with normal, benignhypertrophic, and malignant prostate tissue. PSA is not detected in the serum of males without prostate tissue (because of radical prostatectomy or cystoprostatectomy) or in the serum of most females. The fact that PSA is unique to prostate tissue makes it a suitable marker for monitoring men with cancer of the prostate. PSA is also useful for determining possible recurrence after therapy when used in conjunction with other diagnostic indices. Measurement of serum PSA levels is not recommended as a screening procedure for the diagnosis of cancer because elevated PSA levels also are observed in patients with benign prostatic hypertrophy. However, studies suggest that the measurement of PSA in conjunction with digital rectal examination (DRE) and ultrasound provide a better method of detecting prostate cancer than DRE alone. {1}------------------------------------------------ PSA levels increase in men with cancer of the prostate, and after radicalprostatectomy PSA r SA levels increase in firen with cance. If prostatic tissue remains after surgery or levels routinely fall to the and course to be useful in detecting residual and early metastals nas oboured, to read PSA levels can help determine the success of recurrence of turner. Therefore, ourther treatment, such as radiation, endocrine or prostatootonly, and in the monitoring of the effectiveness of therapy. # 5. Statement of Intended Use The Bayer Diagnostics PSA Immunoassay is for the quantitative determination of prostate The Bayer Diagnostial PDA minutioused) to formalitoring) of patients prostate cancer specific antigen in seram to alle in the management ADVIA Automated Chemiluminescence Systems. # 6. Summary of Technological Characteristics The ACS:180 and ADVIA Centaur PSA assays are a two-site sandwich immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies. The direct offermilammomotio to a polyclonal anti-goat antibody labeled with acridinium not ankibody, in the Solid Phase, is a monoclonal anti-mouse antibody, which is covalently coupled to paramagnetic particles. A direct relationship exists between the amount of PSA present in the patient sample and the amount of relative light units (RLUs) detected by the system ### 7. Performance Data # Sensitivity and Assay Range The ACS: 180 PSA and ADVIA Centaur PSA assays measure total PSA concentrations up to 100 ng/mL (100 µg/L) with a minimum detectable concentration (analytical sensitivity) of 0.06 ng/mL (0.06 [g/L). Analytical sensitivity is defined as the concentration of PSA that corresponds to the RLUs that are two standard deviations greater than the mean RLUs of 20 replicate determinations of the PSA zero standard. #### Accuracy and Method Comparison For 629 samples in the range of 0.06 to 100 ng/mL (0.06 to 100 رو/L), the relationship between the ACS: 180 PSA assay and an alternate method is described by the equation: ACS: 180 PSA = 0.98 (alternate method) + 0.0.118 ng/mL Correlation coefficient (r) = 0.986 For 661 samples in the range of 0.06 to 100 ng/mL (0.06 to 100 ¡q/L), the relationship between the ADVIA Centaur PSA assay and the ACS: 180 PSA assay is described by the equation: ADVIA Centaur PSA = 0.99 (ACS: 180 PSA) - 0.09 ng/mL {2}------------------------------------------------ Correlation coefficient (r) = 0.990 #### Expected Results To confirm the distribution of total PSA in patients, as shown below, serum samples from healthy subjects and patients with various malignant diseases were analyzed using the ACS: 180 PSA reagents. The patients included in this study represent a variety of disease states from active, progressive malignancy to no clinical evidence of disease. The frequency of positive PSA results is significantly lower in patients with no evidence of active disease compared to those with active disease. | Patient<br>Diagnosis | N | 0.0-4.0<br>ng/mL | 4.1-10<br>ng/mL | 10.1-40<br>ng/mL | >40<br>ng/mL | Median<br>PSA<br>(ng/mL) | |----------------------------------|-----|------------------|-----------------|------------------|--------------|--------------------------| | Apparently<br>Healthy | | | | | | | | Female | 100 | 100.0 | 0.0 | 0.0 | 0.0 | < 0.06 | | Male < 40 | 71 | 100.0 | 0.0 | 0.0 | 0.0 | 0.73 | | Male 40-50 | 50 | 100.0 | 0.0 | 0.0 | 0.0 | 0.53 | | Male 50-60 | 54 | 100.0 | 0.0 | 0.0 | 0.0 | 0.61 | | Male 60-70 | 50 | 100.0 | 0.0 | 0.0 | 0.0 | 0.85 | | Male > 70 | 58 | 100.0 | 0.0 | 0.0 | 0.0 | 0.77 | | Total Males | 283 | 100.0 | 0.0 | 0.0 | 0.0 | 0.71 | | Prostate<br>Cancer | | | | | | | | Stage A | 42 | 69.0 | 26.2 | 4.8 | 0.0 | 3.92 | | Stage B | 50 | 60.0 | 32.0 | 8.0 | 0.0 | 3.52 | | Stage C | 43 | 20.9 | 72.1 | 4.7 | 2.3 | 5.25 | | Stage D* | 46 | 56.5 | 21.7 | 19.6 | 2.2 | 3.48 | | Total Prostate | 191 | 51.6 | 38.0 | 9.3 | 1.1 | 4.04 | | Benign<br>Diseases | | | | | | | | Prostate<br>Hypertrophy<br>(BPH) | 152 | 46.7 | 32.9 | 20.4 | 0.0 | 4.37 | | Genitourinary<br>(GU)a | 50 | 90.0 | 8.0 | 2.0 | 0.0 | 1.38 | | Prostatitis | 18 | 27.8 | 5.6 | 5.6 | 61.1 | 125.9 | | Rheumatoid<br>Factor | 5 | 100.0 | 0.0 | 0.0 | 0.0 | 0.58 | #### % Distribution of PSA by Diagnostic Category * Six of the these samples were from untreated patients, the remaining samples were patients under treatment {3}------------------------------------------------ # % Distribution of PSA by Diagnostic Category | Patient | | 0.0-4.0 | 4.1-10 | 10.1-40 | >40 | Median<br>PSA | |------------------|----|---------|--------|---------|-------|---------------| | Diagnosis | N | ng/mL | ng/mL | ng/mL | ng/mL | (ng/mL) | | Other Cancers | | | | | | | | Breast | 10 | 100.0 | 0.0 | 0.0 | 0.0 | 0.08 | | Renal | 6 | 100.0 | 0.0 | 0.0 | 0.0 | 0.37 | | Pulmonary | 10 | 100.0 | 0.0 | 0.0 | 0.0 | 0.08 | | Misc. GU | 39 | 92.3 | 5.1 | 2 6 | 0.0 | 0.42 | | Gastrointestinal | 12 | 91.7 | 0.0 | 0 0 | 8.3 | 0.90 | | Other | 18 | 100.0 | 0.0 | 0 0 | 0.0 | 0.45 | #### Precision , : For the ACS: 180 eight samples were assayed 3 times in 6 assays, on each of 4 systems (n = 72 for each samples were abouted of the following results were shteined; obtained: | Mean<br>(ng/mL) | Mean<br>(ug/L) | Within-run<br>% CV | Run-to-run<br>% CV | Total<br>% CV | |-----------------|----------------|--------------------|--------------------|---------------| | 0.70 | 0.70 | 3.4 | 3.2 | 5.9 | | 0.91 | 0.91 | 3.4 | 3.6 | 5.3 | | 1.83 | 1.83 | 2.8 | 3.3 | 5.0 | | 17.55 | 17.55 | 2.8 | 2.7 | 4.2 | | 18.23 | 18.23 | 2.9 | 3.1 | 4.6 | | 29.73 | 29.73 | 3.2 | 3.0 | 5.1 | | 54.34 | 54.34 | 3.5 | 3.3 | 5.3 | | 76.25 | 76.25 | 3.7 | 3.4 | 6.3 | For the ADVIA Centaur six samples were assayed 3 times in 8 runs, on each of 4 systems (n = 24 for each sample), over a period of 3 days. The following results were obtained | Mean<br>(ng/mL) | Mean<br>(µg/L) | Within-run<br>% CV | Run-to-run<br>% CV | Total<br>% CV | |-----------------|----------------|--------------------|--------------------|---------------| | 0.44 | 0.44 | 4.8 | 4.05 | 5.97 | | .708 | .708 | 3.08 | 2.07 | 3.71 | | 1.831 | 1.831 | 2.09 | 4.67 | 5.12 | | 1.934 | 1.934 | 2.08 | 1.56 | 2.60 | | 11.308 | 11.308 | 2.97 | 3.61 | 4.68 | | 17.706 | 17.706 | 2.29 | 2.40 | 3.31 | {4}------------------------------------------------ DEPARTMENT OF HEALTH & HUMAN SERVICES Image /page/4/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features an abstract eagle design with three stylized lines representing the bird's body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the eagle, indicating the department's name and national affiliation. # APR 1 3 2000 Food and Drug Administration 2098 Gaither Road Rockville MD 20850 Mr. William J. Pignato Director or Regulatory Affairs Bayer Diagnostics Corporation 63 North Street Medfield, Massachusetts 02052 Re: K994221 > Trade Name: Bayer Diagnostics Corporation ACS: 180/ADVIA Centaur PSA Assay Regulatory Class: II Product Code: LTJ Dated: March 10, 2000 Received: March 15, 2000 Dear Mr. Pignato: 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 legally marketed predical (or the multiple) for the multiplish for use prior to May 28, 1976, the enactment date of the Medical Innersiale United States 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 Kegulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, 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 (FTA) 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. {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 parketed 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" (21CFR 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 (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html". Sincerely yours, Steven Putman 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 0 {6}------------------------------------------------ Page _______ of __ 510(k) Number (if known): K994221 Device Name: Bayer Diagnostics ACS:180 and ADVIA Centaur PSA Assay # Indications for Use: The Bayer Diagnostics PSA Immunoassay is for the quantitative serial determination of prostate specific antigen in human serum and to aid in the managenent (monitoring) of patients with prostate cancer Qine E. Macher (Division Sign-Off) Division of Clinical Laboratory Devi 510(k) Number - (PLEASE DO NOT WRITE BELOW THIS LINE--CONTINUE ON ANOTHER PAGE, IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE) | Prescription Use | | |----------------------|--| | Counter Use | | | (Per 21 CFR 801.109) | | | Format 1-2-96) | | OR Over-The- (Optional