(30 days)
Not Found
No
The summary describes a FISH-based diagnostic kit and its performance metrics, with no mention of AI, ML, or related concepts like image processing or training/test sets for algorithmic models.
No.
The device is for monitoring for tumor recurrence and provides diagnostic results, which is an assessment, not a treatment.
Yes
The device is described as a "Bladder Cancer Recurrence Kit" and its "Intended Use" states it is "designed to detect aneuploidy...in urine specimens from subjects with transitional cell carcinoma of the bladder" and its results are "intended for use as a noninvasive method for monitoring for tumor recurrence." These functions are consistent with a diagnostic device that aids in identifying or monitoring disease.
No
The device description explicitly states it is a "Kit" based on "fluorescence in situ hybridization (FISH) DNA probe technology" and includes "fluorescently labeled nucleic acid probes" and a "4-color, four-probe mixture". These are physical components, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the kit is "designed to detect aneuploidy... via fluorescence in situ hybridization (FISH) in urine specimens". It also states that the results are "intended for use as a noninvasive method for monitoring for tumor recurrence". This clearly indicates that the device is used to perform a test on a biological specimen (urine) to provide information about a patient's health status (monitoring for tumor recurrence).
- Device Description: The description details the components of the kit, which are "fluorescently labeled nucleic acid probes for use in in situ hybridization assays on urine specimens fixed on slides". This confirms that the device is a reagent kit used for an in vitro test.
- Input Imaging Modality: While it mentions FISH, which involves imaging, the core function of the device is the preparation and labeling of the biological sample for analysis, which is characteristic of an IVD.
- Performance Studies: The document describes performance studies conducted on urine specimens to evaluate the device's specificity and agreement with standard of care, which are typical evaluations for IVD devices.
The definition of an In Vitro Diagnostic (IVD) is a medical device that is used to perform tests on samples such as blood, urine, or tissue, taken from the human body, to detect diseases, conditions, or infections. The UroVysion Bladder Cancer Recurrence Kit fits this definition perfectly.
N/A
Intended Use / Indications for Use
The UroVysion Bladder Cancer Recurrence Kit (UroVysion Kit) is designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens from subjects with transitional cell carcinoma of the bladder. Results from the UroVysion Kit are intended for use as a noninvasive method for monitoring for tumor recurrence in conjunction with cystoscopy in patients previously diagnosed with bladder cancer.
Product codes (comma separated list FDA assigned to the subject device)
MMW
Device Description
The UroVysion Kit is based upon fluorescence in situ hybridization (FISH) DNA probe technology. The UroVysion probes are fluorescently labeled nucleic acid probes for use in in situ hybridization assays on urine specimens fixed on slides. The UroVysion Kit consists of a 4-color, four-probe mixture of DNA probe sequences homologous to specific reaions on chromosomes 3. 7. 9. and 17. The UroVysion probe mixture consists of Chromosome Enumeration Probe (CEP®) 3 SpectrumRed™, CEP 7 SpectrumGreen™, CEP 17 SpectrumAqua™ and Locus Specific Identifier (LSI®) 9p21 SpectrumGold™.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Bladder
Indicated Patient Age Range
36 - 98 years
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
A multi-center, prospective study was conducted to establish the specificity of the UroVysion test in urine from healthy volunteers and urology patients without prior history or clinical evidence of bladder cancer, which served as the test set for specificity. Total of 315 patient visits, 309 usable office visits. FISH assay and analysis on the 309 usable office visits resulted in informative results in 230 specimens on the first attempt. The hybridization efficiency for the first assay attempt was 93%. Repeat assays were conducted on 67 specimens; 12 of these 79 specimens had insufficient volume remaining to repeat the assay. Of the 67 repeat assays, 45 yielded informative results, leaving 34 specimens classified as "non-informative" (including 12 cases with insufficient volume for repeat assay). In summary, 89% of the cases yielded an informative result on the first or second attempt. The patient population is summarized by category in Table 3. Patients with medical conditions falling in multiple categories and/or multiple conditions within the same category were counted for each individual condition. For "unique cases", each patient was counted only once, regardless of the number of medical conditions present.
For performance against the standard of care, a multi-center, prospective, longitudinal study was conducted on patients previously diagnosed with bladder cancer. The comparative reference was cystoscopy with histology confirmation for positive or suspicious cystoscopies. If a patient had a positive cystoscopy but histology was absent (e.g., the lesion was fulgurated), then the specimen was considered positive for bladder cancer. If a test had a suspicious cystoscopy but histology was absent, then the case was omitted from analysis. A total of 309 patient visits, 251 usable office visits. Urine processing and analysis were conducted at one centralized testing laboratory. FISH assay and analysis on the 251 usable office visits resulted in 234 informative results, representing 176 unique patients. For patients who experienced a recurrence during the trial (as determined by cystoscopy and/or histology), the first positive visit was used. For non-recurring patients, the last negative visit was used for those patients with more than one visit. Demographic data for the 176 unique patients are summarized in Table 5. FISH assays on 70% (175/251) of the eligible study specimens were informative on the first attempt. Repeat assays were conducted on 70 specimens.
For substantial equivalence, specimens from each of the 176 unique patients (first positive, last negative office visit) were also analyzed by the BTAstat test and cytology.
For the longitudinal study, office visit information (without FISH or BTAstat testing) was collected for patients who had not experienced a relapse (cystoscopy/histology negative) for approximately 1 year from their last visit during the main phase of the trial. Of the 114 eligible patients, office visit information was collected from 105. A total of 335 patient visits were reported, resulting in 299 usable office visits, representing 104 unique patients. For patients who experienced a recurrence (as determined by cystoscopy/histology), the first positive visit was used. For non-recurring patients, the last negative visit was used for those patients with more than one visit.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Reproducibility:
- Reproducibility of Bladder Carcinoma Cell Culture Specimens: Analysis of signal distributions for CEP 3, CEP 7, CEP 17, and LSI 9p21 were assessed for inter-site (4 sites) reproducibility on slides prepared from 4 different bladder carcinoma cell lines (one normal, 3 abnormal). Each site assayed four replications of the same specimen on each of four assay days. Each specimen was evaluated by one observer at each site.
- Sample Size: 80 specimens (76 informative on first attempt).
- Key Results: Informative results were obtained in 95.0% (76/80) of specimens on the first attempt. The mean, standard deviation, and percent CV for the average number of signals for the four probes showed narrow ranges, except for LSI 9p21 in specimen 2 due to its absence (mean 0.03, CV 220.44%), but this specimen was still easily classified as having a loss. There were no false negative results in this study of human bladder carcinoma cell lines (48/48 evaluations of abnormal specimens were positive). One out of 16 evaluations of the normal specimen was classified as positive.
Specificity Study:
- Study Type: Multi-center, prospective study to establish the specificity of the UroVysion test in urine from healthy volunteers and urology patients without prior history or clinical evidence of bladder cancer.
- Sample Size: 315 patient visits, with 309 usable office visits. 230 specimens yielded informative results on the first attempt.
- Key Results: The overall specificity was 93.0% (332/357). Specificity among unique cases was 94.5% (260/275). Specificity among healthy patients was 100% (59/59). False positive results were found in 15 patients across various conditions.
Performance vs. Standard of Care Study:
- Study Type: Multi-center, prospective, longitudinal study to define performance characteristics relative to cystoscopy followed by histology for monitoring disease recurrence.
- Sample Size: 309 patient visits, with 251 usable office visits, representing 176 unique patients.
- Key Results: Overall, FISH analysis with the UroVysion Kit demonstrated:
- Percent agreement of positive results = 71.0% (95% Cl = 58.1% - 81.8%)
- Percent agreement of negative results = 65.8% (95% Cl = 56.3% - 74.4%)
- Overall Agreement = 67.6% (95% CI = 60.2% - 74.5%)
- (+) Predictive Value = 53.0% (95% CI = 41.7%-64.1%)
- (-) Predictive Value = 80.6% (95% CI = 71.1% - 88.1%)
- Prevalence = 35.2% (95% CI = 28.2% - 42.8%)
- p = ChiSq = 0.0031) and Wilcoxon (Chi-Square = 10.6166, DF = 1, Prob>ChiSq = 0.0011).
HYBrite/VP 2000 Validation (Manual vs. Semi-Automation):
- Study Type: Validation study to determine if the recommended specimen pretreatment protocol performed similarly when done manually or semi-automated using the VP2000 Sample Processor and HYBrite instruments.
- Sample Size: Three human urine pools from normal donors, spiked with 29 different substances at two concentrations.
- Key Results: Quality evaluations showed equivalent results using the UroVysion Kit and FISH Pretreatment Kit for all concentrations and across all three instrument set-ups. All compounds and preservatives performed within 2 standard deviations, supporting the conclusion that manual and semi-automated methods are equivalent.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Specificity:
- Overall Specificity: 93.0% (332/357)
- Unique Patients Specificity: 94.5% (260/275)
- Healthy Specificity: 100% (59/59)
- Non-Healthy Specificity: 93.1% (201/216)
- Smokers Specificity: 95.2% (40/42)
- Non-Smokers Specificity: 94.7% (234/247)
Performance vs. Standard of Care (Cystoscopy/Histology):
- Agreement of (+) results = 71.0% (95% Cl = 58.1% - 81.8%)
- Agreement of (-) results = 65.8% (95% Cl = 56.3% - 74.4%)
- Overall Agreement = 67.6% (95% CI = 60.2% - 74.5%)
- (+) Predictive Value = 53.0% (95% CI = 41.7%-64.1%)
- (-) Predictive Value = 80.6% (95% CI = 71.1% - 88.1%)
- Prevalence = 35.2% (95% CI = 28.2% - 42.8%)
- For patients on BCG Therapy within 3 months:
- Agreement of (+) results = 92.3% (95% CI = 64.0% - 99.8%)
- Agreement of (-) results = 61.5 % (95% CI = 40.6% - 79.8%)
- Overall Agreement = 71.8% (95% CI = 55.1% - 85.0%)
- (+) Predictive Value = 54.5% (95% CI = 32.2% - 75.6%)
- (-) Predictive Value = 94.1% (95% CI = 71.3% - 99.9%)
- Prevalence = 33.3% (95% CI = 19.1% - 50.2%)
Hypothetical Predictive Values (based on 71.0% Agreement (+) and 65.8% Agreement (-)):
- Prevalence 10%: PPV = 18.7%, NPV = 95.3%
- Prevalence 20%: PPV = 34.2%, NPV = 90.1%
- Prevalence 30%: PPV = 47.1%, NPV = 84.1%
Comparison of Methods (FISH, BTAstat, Cytology) overall:
- FISH: Agreement of (+) Results = 71.0%, Agreement of (-) Results = 65.8%, Overall Agreement = 67.6%
- BTAstat: Agreement of (+) Results = 50.0%, Agreement of (-) Results = 69.3%, Overall Agreement = 62.5%
- Cytology: Agreement of (+) Results = 26.2%, Agreement of (-) Results = 89.1%, Overall Agreement = 66.7%
Comparison of Methods (FISH, BTAstat, Cytology) for BCG Treatment:
- FISH: Agreement of (+) Results = 92.3%, Agreement of (-) Results = 61.5%, Overall Agreement = 71.8%
- BTAstat: Agreement of (+) Results = 69.2%, Agreement of (-) Results = 42.3%, Overall Agreement = 51.3%
- Cytology: Agreement of (+) Results = 30.8%, Agreement of (-) Results = 84.6%, Overall Agreement = 66.7%
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.
Not Found
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).
Not Found
§ 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.
0
JAN 2 2 2004
Image /page/0/Picture/1 description: The image shows a sequence of alphanumeric characters, specifically "KO33982-". The characters are written in a simple, sans-serif font, and they appear to be handwritten. The last character is a dash.
Vysis, Inc. 3100 Woodcreek Dr. Downers Grove, IL 60515 Tel: 630 271-7083 Fax: 630 271-7438 Contact: Kerry J. Flom, Ph.D.
510(k) Summary: Safety and Effectiveness Information for the UroVysion™ Bladder Cancer Recurrence Kit
December 19, 2003
Trade Name Vysis® UroVysion™ Bladder Cancer Recurrence Kit
Common or Usual Name Fluorescence in situ hybridization (FISH) reagents
Classification Name Class II IVD Device
Predicate Legally Marketed Device Bard® (Bion) BTAstat™ Test
Description of the Device
The UroVysion Kit is based upon fluorescence in situ hybridization (FISH) DNA probe technology. The UroVysion probes are fluorescently labeled nucleic acid probes for use in in situ hybridization assays on urine specimens fixed on slides. The UroVysion Kit consists of a 4-color, four-probe mixture of DNA probe sequences homologous to specific reaions on chromosomes 3. 7. 9. and 17. The UroVysion probe mixture consists of Chromosome Enumeration Probe (CEP®) 3 SpectrumRed™, CEP 7 SpectrumGreen™, CEP 17 SpectrumAqua™ and Locus Specific Identifier (LSI®) 9p21 SpectrumGold™.
Intended Use
The UroVysion Bladder Cancer Recurrence Kit (UroVysion Kit) is designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens from subjects with transitional cell carcinoma of the bladder. Results from the UroVysion Kit are intended for use as a noninvasive method for monitoring for tumor recurrence in conjunction with cystoscopy in patients previously diagnosed with bladder cancer.
1
Different Technological Characteristics
Both the UroVysion Kit and the BTAstat test use the same specimen collection and preparation techniques in clinical practice. Thus, no new issues of safety with respect to patient care are introduced by the FISH technique; both the UroVysion Kit and the BTAstat test start with the same patient specimen (i.e., voided urine).
The major differences between the two tests are that they detect different substances and use different detection methods. Briefly, the UroVysion Kit uses DNA probes for specific regions on chromosomes 3, 7, 9 and 17 that bind to the target chromosomes by the DNA hybridization reaction. The actual binding mechanism of the UroVysion Kit is via specific complementary base pairing. In contrast, the BTAstat test is a lateral flow assay that detects the presence of bladder tumor associated antigen through antigen-specific antibodies. Also, the necessary visual interpretation of the results of the UroVysion Kit and of the BTAstat test is different. For the BTAstat test, urine is allowed to react with a colloidal gold-coniuqated antibody and the results are determined qualitatively by the presence or absence of a line on the test stick. For the UroVysion Kit, the analyst visually recognizes chromosomes 3, 7 and 17, and the 9p21 locus by the fluorescent signal carried by the DNA probe mixture.
Even though the technological characteristics are different between the BTAstat test (antigen test) and the UroVysion test (DNA probe test), both test are intended for use to monitor for the recurrence of bladder cancer from voided urine specimens. The overall performance of the UroVysion test was demonstrated to be substantially equivalent.
Safety and effectiveness issues evaluated for the UroVysion Kit included the following: prospective, comparative methods evaluation for monitoring bladder cancer recurrence; specificity evaluation in healthy and unhealthy patients (without previous diagnosis of bladder cancer); interference assessment; and reproducibility studies.
2
Non-Clinical Parameters
Hybridization Efficiency
On the ProbeChek™ quality control slides run in conjunction with the clinical trials, 1.5% (4/261) of the targets failed due to lack of hybridization. These slides are prepared from cultured human bladder carcinoma (positive target) and normal lymphoblast (negative target) cell lines, and represent the best-case scenario for hybridization efficiency. Thus, under these conditions, the hybridization efficiency was found to be 98.5%, with 275 for individual disease categories.
3 Non-GU cancers included breast (1), colon (1), and leukemia (1)
Based on the patient population in this study, the UroVysion test demonstrated an overall specificity of 93.0% (332/357), with a 100% specificity (59/59) among healthy patients. The specificity among unique cases was 94.5% (260/275). The false positive results found in 15 patients represented the following categories (note that some patients had health conditions falling into multiple disease categories); non-Special 510(k): Device Modification Attachment 5 Vysis® UroVysion™ Bladder Cancer Recurrence Kit Page 66 Volume I
9
genitourinary (GU) benign diseases (3), non-GU cancer (2), GU diseases (15), and GU cancer (5). These results indicate that the test is highly specific in this patient group, which reinforces the fact that FISH does not generate artificial aneuploidy determinations; the FISH probes react only with the intended chromosomes.
Performance vs. Standard of Care
Study Summary
A multi-center, prospective, longitudinal study was conducted to further define the performance characteristics of the UroVysion Kit relative to cystoscopy followed by histology, the standard of care for monitoring for disease recurrence in patients previously diagnosed with bladder cancer. The comparative reference used for all percent agreement calculations was cystoscopy with histology confirmation for positive or suspicious cystoscopies. If a patient had a positive cystoscopy but histology was absent (e.g., the lesion was fulgurated), then the specimen was considered positive for bladder cancer. If a test had a suspicious cystoscopy but histology was absent, then the case was omitted from analysis. A total of 309 patient visits were conducted at 21 investigation sites, resulting in 251 usable office visits. The 58 unusable visits included 17 that did not meet the eligibility criteria, 16 with insufficient urine volume, 10 with suspicious cystoscopies but no histology, and in 15 cases urine was not sent to the testing laboratories. Urine processing and analysis were conducted at one centralized testing laboratory. FISH assay and analysis on the 251 usable office visits resulted in 234 informative results, representing 176 unique patients. For patients who experienced a recurrence during the trial (as determined by cystoscopy and/or histology), the first positive visit was used (i.e., the visit at which the diagnosis of recurrence was established). For the non-recurring patients, the last negative visit was used for those patients with more than one visit. The demographics for the 176 unique patients are summarized in Table 5.
| Table 5 | |
|---|---|
| Patient Demographics | |
| Sex | |
| Male | 132 |
| Female | 44 |
| Race | |
| Caucasian | 153 |
| African American | 3 |
| Hispanic | 3 |
| Other | 13 |
| Unknown | 4 |
| Age | |
| Range | 36 - 98 years |
| Average | 71 years |
10
Technical Performance: Informative vs. Non-Informative Results
FISH assays on 70% (175/251) of the eligible study specimens were informative on the first attempt. Of the 76 specimens that failed to vield informative results on the first attempt, only 26 were due to hybridization failures. The hybridization efficiency for the first assay attempt was 87%. The remaining non-informative assays were the result of poor specimen quality (e.g., insufficient number of cells) or technical error (e.g., broken slide).
Repeat assays were conducted on 70 specimens; six of the 76 specimens had insufficient volume remaining to repeat the assay. Of the 70 repeat assays, 59 vielded informative results, leaving 17 specimens classified as "non-informative" (including the 6 cases with insufficient volume for repeat assay). In summary. over 93% of the cases vielded an informative result on the first or second attempt.
Performance vs. Standard of Care
Of the eligible patients with informative FISH results, 62 were positive by cystoscopy/histology. A breakdown of the number of tumors by stage and grade is shown in Table 6.
| Table 6
| Number of Tumors, by Stage and Grade | ||||||
|---|---|---|---|---|---|---|
| Tumor Grade | ||||||
| Tumor | ||||||
| Stage | ND | 1 | 2 | 3 | Unknown | Total |
| ND | 11 | 0 | 0 | 0 | 0 | 11 |
| Ta | O | 20 | ് | 6 | 0 | 32 |
| T1 | 0 | 0 | 2 | 3 | ട് | |
| T2 | 0 | 0 | 0 | 2 | ﻟﻠﺘﺨﻠﻴﻔﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘ | |
| Tis | O | O | O | 7 | 0 | 1 |
| Unknown | 0 | 2 | r | O | 0 | 3 |
| Total | 11 | 22 | ರಿ | 18 | 2 | 62 |
ND = not assigned or no biopsy
Table 7 shows the performance of the UroVysion Kit, relative to cystoscopy / histology, by tumor stage and grade for all cases with biopsy information available. The UroVysion Kit showed greatest agreement of positive results (100%) among the most severe tumors (T2 and Tis), when compared to cystoscopy/histology.
11
Table 7 Comparison of UroVvsion vs. Cystoscopy/Histology for Detection of Bladder Cancer Recurrence by Tumor Stage and Grade* Agreement of (+) Results (%)
| Stage: | |
|---|---|
| All | 36/48 (75.0%) |
| Ta, Grade 1 | 11/20 (55.0%) |
| Ta, Grade 2,3 | 10/12 (83.3%) |
| T1 | 5/6 (83.3%) |
| T2 | 3/3 (100%) |
| Tis | 7/7 (100%) |
| Grade: | |
| All | 36/49 (73.5%) |
| 1 | 12/22 (54.5%) |
| 2 | 7/9 (77.8%) |
| 3 | 17/18 (94.4%) |
*Biopsy was not performed in 11 cases. In addition, no stage was assigned in 3 cases and no grade in 2.
Table 8 shows a comparison of the performance of the UroVysion Kit relative to cystoscopy followed by histology. Overall, FISH analysis with the UroVysion Kit demonstrated a percent agreement of positive results of 71.0% and a percent agreement of negative results of 65.8% when compared to the results of cystoscopy, followed by histology in the case of positive or suspicious cystoscopy (Note: A positive cystoscopy without a biopsy was considered positive in this analysis).
| Table 8 |
|---|
| Comparison of UroVysion vs. Cystoscopy/Histology |
| for Detection of Bladder Cancer Recurrence |
| Custo/Histo |
| ે જિણા તરીકે છ | ||||
|---|---|---|---|---|
| + | Total | |||
| દાદમ | + | 44 | 39 | 83 |
| 18 | 75 | 03 | ||
| Total | 62 | 114 | 176 | |
| SER FRE ( ) " = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = | AL AALY |
Agreement of (+) results = 71.0% (95% Cl = 58.1% - 81.8%) Agreement of (-) results = 65.8% (95% Cl = 56.3% - 74.4%) Overall Agreement = 67.6% (95% CI = 60.2% - 74.5%) (+) Predictive Value = 53.0% (95% CI = 41.7%-64.1%) (-) Predictive Value = 80.6% (95% CI = 71.1% - 88.1%) Prevalence = 35.2% (95% CI = 28.2% - 42.8%) p = ChiSq = 0.0031) and Wilcoxon (Chi-Square = 10.6166, DF = 1, Prob>ChiSq = 0.0011).
20
HYBrite/VP 2000 Validation
The VP2000 is considered to be a class I, exempt device according to 21 CFR & THE VF 2000 is considered to be a labor, and 21 CFR § 864.3875 Automated tissue ob4.3800 Automation of the VP2000 is consistent with both of the above processor. The function of the VT 2008 is consister modifications the device is paragraphs from the OF A. "Indocution OEM device bought and sold by Zeiss during the past decade as a class I device for cytology laboratories.
The paragraphs from the CFR are reproduced below:
21 CFR § 864.3800 Automated slide stainer. (a) Identification. An automated slide stainer is a device used to stain histology, An adomatod ollustically slides for diagnosis. (b) Classification. Class I. The device is exempt from the premarket notification procedures in Subpart E of Part 807 of this chapter.
21 CFR § 864.3875 Automated tissue processor. (a) Identification. An automated tissue processor is an automated system used to process tissue specimens for examination through fixation, dehydration, and infiltration. (b) Classification. Class I. The device is exempt from the premarket notification procedures in Subpart E of Part 807 of this chapter.
A validation study was conducted to determine if the recommended specimen / validation otably for the UroVysion Kit performed the same pretreatment protocol and technician or by semi-automated using the VP2000 Sample Processor and HYBrite instruments.
Study specimens consisted of three human urine pools prepared from voided urine specimens obtained from normal donors. Study specimens used in the anne Specificans obtains obtains (see Appendix B for protocol and , tody intentional were also used as part of this study. Each of the 29 substances stady report, were aliquots of each of the three pools at two different which word oplical in three separate VP-2000 and HYBrite instruments and compared to results obtained in the manual study.
Quality evaluations from samples of the 23 different compounds and 6 &uality of charactions it equivalent results using the UroVysion Kit and FISH Pretreatment Kit for all concentrations tested and across all three instrument set-ups.
Normal urine pools (unspiked) and manual assay results from the Interference Study Protocol, 99-402R were used as controls. All compounds and Otudy 1 10.000, 00 Trod in Table 20 performed within 2 standard deviations or preservatives from hools, supporting the conclusion that the manual and semiautomated methods are equivalent.
Attachment 5 Page 78
21
| Substance | Concentrations | Results- Manual vs
Semi-Automation |
|--------------------------------------|---------------------------------------------------------------------------|---------------------------------------|
| | Possible Urine Constituents | |
| Albumin | 0.5 g/dL and 1.0 g/dL | Equivalent. |
| Ascorbic Acid | 2.5 g/dL and 5 g/dL | Equivalent. |
| Bilirubin (unconjugated) | 1 mg/mL and 2 mg/mL | Equivalent. |
| Hemoglobin | 50 mg/mL and 100 mg/mL | Equivalent. |
| IgG | 5 mg/dL and 10 mg/dL | Equivalent. |
| Red Blood Cells (human) | $5 x 10^5$ cells/mL and $1 x 10^6$ cells/mL | Equivalent. |
| White Blood Cells (human) | $5 x 10^5$ cells/mL and $1 x 10^6$ cells/mL | Equivalent. |
| Sodium Chloride | 365 mg/dL and 730 mg/dL | Equivalent. |
| Uric Acid | 125 mg/dL and 250 mg/dL | Equivalent. |
| Caffeine | 58.5 mg/dL and 117 mg/dL | Equivalent. |
| Ethanol | 0.5% (v/v) and 1% (v/v) | Equivalent. |
| Nicotine | 14 mg/dL and 28 mg/dL | Equivalent. |
| | Possible Microbial Contaminants | |
| Candida albicans | $1.25 x 10^{10}$ CFU/mL and $2.5 x 10^{10}$ CFU/mL | Equivalent. |
| Escherichia coli | $1.25 x 10^{10}$ CFU/mL and $2.5 x 10^{10}$ CFU/mL | Equivalent. |
| Pseudomonas aerugenosa | $1.25 x 10^{10}$ CFU/mL and $2.5 x 10^{12}$ CFU/mL | Equivalent. |
| | Therapeutic Agents | |
| Acetaminophen | 2.6 g/dL and 5.2 g/dL | Equivalent. |
| Acetylsalicylic Acid | 2.6 g/dL and 5.2 g/dL | Equivalent. |
| Ampicillin | 300 mg/dL and 600 mg/dL | Equivalent. |
| BCG | 10 mg/dL and 20 mg/dL | Equivalent. |
| Doxorubicin-HCI | 5 mg/dL and 10 mg/dL | Equivalent. |
| Mitomycin C | 5 mg/dL and 10 mg/dL | Equivalent. |
| Nitrofurantoin | 25 mg/dL and 50 mg/dL | Equivalent. |
| Phenazopyridine-HCI | 100 mg/dL and 200 mg/dL | Equivalent. |
| Thiotepa | 5 mg/dL and 10 mg/dL | Equivalent. |
| Trimethoprin | 25 mg/dL and 50 mg/dL | Equivalent. |
| | Preservatives | |
| Vysis, Inc. standard:
2% Carbowax | 2% Carbowax/50% ethanol solution (33 ml
urine with 17 mL preservative) | Equivalent. |
| UroCor, Inc. fixative | 50/50 with urine | Equivalent. |
| CytRichRed (Autocyte) | 50/50 with urine | Equivalent. |
| Saccamono's solution | 50/50 with urine | Equivalent. |
| PreservCyt solution (Cytyc) | 50/50 with urine | Equivalent. |
| 100% Ethanol | 50/50 with urine | Equivalent. |
Table 20 Manual versus Semi-Automation Study Results
Conclusions
The nonclinical and clinical studies described in this document demonstrate that the nonomical and UroVysion Kit is safe and effective. The performance of the IroVysion Kit is also supported by the Vysis Quality Control procedures. When Gro Frontision Kit is used as instructed in the package insert, the above 1 statements describe its performance.
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Image /page/22/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines representing the wings and a stylized tail.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JAN 2 2 2004
Kerry J. Flom, Ph.D. Senior Director Clinical Research and Regulatory Submissions Vysis, Inc. 3100 Woodcreek Drive Downers Grove, IL 60515
Re: K033982
Trade/Device Name: Vysis® UroVysion™ Bladder Cancer Kit Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Code: MMW Dated: December 19, 2003 Received: December 23, 2003
Dear Dr. Flom:
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. 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2
This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer 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,
Fiven Autman, M.D.
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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ATTACHMENT 3
Indications for Use Statement
K033982 510(k) Number (if known):
Vysis® UroVysion™ Bladder Cancer Kit DEVICE NAME:
INDICATIONS FOR USE:
The UroVysion Bladder Cancer Recurrence Kit (UroVysion Kit) is designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens from subjects with transitional cell carcinoma of the bladder. Results from the Uro Vysion Kit are intended for use as a noninvasive method for monitoring for turnor recurrence in conjunction with cystoscopy in patients previously diagnosed with bladder cancer.
Note: No change from the current, cleared indications for use (K013785)
Donald J. B
(Division Sign-OH) (Office of In Vitro Diagnostic Devices Evaluation and Safety 510(k) Number 4033882
(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 (Optimal Format 1-2-96)
Special 510(k): Device Modification Vysis® UroVysion™ Bladder Cancer Recurrence Kit Volume I
Attachment 3 Page 55