(88 days)
Not Found
No
The device description focuses on standard molecular diagnostic techniques (nucleic acid extraction, PCR amplification, and fluorescent detection) and automated data management for assigning predefined results based on quantitative thresholds. There is no mention of AI or ML algorithms being used for analysis, interpretation, or decision-making beyond these standard methods.
No
This device is an in vitro diagnostic test for quantitating BKV DNA, intended to aid in the management of BKV in transplant patients by providing diagnostic information, not to directly treat or prevent a disease.
Yes
Explanation: The device is an in vitro nucleic acid amplification test intended for the quantitation of BKV DNA to aid in the management of BKV in transplant patients. This directly supports diagnosis and monitoring of a medical condition.
No
The device is an in vitro diagnostic (IVD) test that includes reagents (master mix, probes, etc.) and is performed on a specific hardware system (cobas® 6800/8800 Systems). While it includes software for data management and analysis, it is not solely software.
Based on the provided text, the device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the cobas® BKV is an in vitro nucleic acid amplification test. It is designed to quantify BKV DNA in human EDTA plasma and urine, which are biological samples taken from the body.
- Device Description: The description details the process of sample preparation (nucleic acid extraction and purification) and subsequent PCR amplification and detection. These are all procedures performed in vitro (outside the living body) on biological specimens.
- Purpose: The test is intended to aid in the management of BKV in transplant patients by providing quantitative measurements of BKV DNA. This information is used by healthcare professionals in conjunction with other clinical findings to make patient management decisions.
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, to detect diseases, conditions, or infections. The cobas® BKV clearly fits this definition.
N/A
Intended Use / Indications for Use
cobas® BKV is an in vitro nucleic acid amplification test for the quantitation of BKV) DNA in human EDTA plasma and urine stabilized in cobas® PCR media on the cobas® 6800/8800 Systems.
In EDTA plasma, cobas® BKV is intended for use as an aid in the management of BKV in transplant patients. In patients undergoing monitoring of BKV in EDTA plasma, serial DNA measurements can be used to indicate the need for potential treatment changes and to assess viral response to treatment.
In urine stabilized in cobas® PCR Media, cobas® BKV is intended for use as an aid in the management of BKV in transplant patients.
The results from cobas® BKV are intended to be read and analyzed by a qualified licensed healthcare professional in conjunction with clinical signs and symptoms and relevant laboratory findings. Test results must not be the sole basis for patient management decisions.
cobas® BKV is not intended for use as a screening test for blood products or human cells, tissues, and cellular and tissue-based products (HCT/Ps).
Product codes
QLX
Device Description
cobas® BKV (Figure 1) is based on fully automated sample preparation (nucleic acid extraction and purification) followed by PCR amplification and detection. The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software which assigns test results for all tests as either target not detected, BKV DNA detected ULoQ (upper limit of quantitation), or a value in the linear range LLoQ 0.05%), were shown not to interfere. Talcum powder at ≤ 0.05% showed no interference.
Cross contamination
- Study Type: Cross-contamination rate study.
- Sample Size: 240 replicates of a BKV-negative matrix sample and 225 replicates of a high titer BKV DNA urine sample. Five runs performed.
- Key Results: Cross-contamination rate of 0.0% (upper one-sided 95% confidence interval 1.24%).
Reproducibility of cobas® BKV
- Study Type: Reproducibility study.
- Sample Size: 270 tests per concentration (not including controls) from a positive and a negative sample panel. Conducted at 3 testing sites, using 3 reagent lots. Two operators at each site tested each reagent lot for 5 days, two runs per day, 3 replicates per panel member per run.
- Key Results: Acceptable clinical reproducibility. System detected 100% of the 3 x LLoQ samples. Equivalency between cobas® 6800 and cobas® 8800 Systems. The estimated 95% confidence limits (CLs) for the difference between 2 measurements from the same subject were within ± 0.20 log10 copies/mL. The system showed a 99.26% negative percent agreement with a CI of 97.3% to 99.9%.
Clinical Performance of cobas® BKV
- Study Type: Clinical performance evaluation comparing cobas® BKV with a laboratory developed test (LDT).
- Sample Size: 308 neat urine samples stabilized in cobas® PCR Media from 84 transplant subjects for concordance analysis. 153 neat urine samples from 55 transplant subjects for correlation analysis.
- Key Results: Concordance was evaluated using different clinical thresholds. For Target Not Detected by LDT, the column agreement was 100.0%. For 3.0 to 3.9, column agreement was 99.4%. The NPA was 100% with the 95% Exact CI of 94.1% to 100% for BKV DNA-negative samples (61 valid samples out of 66). Bias plot analysis indicated a systematic difference between both assays that is constant across the overlapping linear range. The 95% CI of the intercept of the fitted line in the bias plots was (0.168 to 0.488), within ±0.5 log10 IU/mL.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- LoD: 95% hit rate at 12.2 IU/mL for neat urine (PROBIT).
- Linearity Accuracy: within ± 0.2 log10.
- Cross-contamination rate: 0.0% (upper one-sided 95% confidence interval 1.24%).
- Negative Percent Agreement (NPA): 99.26% (CI of 97.3% to 99.9%) for reproducibility study; 100% (95% Exact CI of 94.1% to 100%) for clinical performance study on BKV DNA-negative samples.
- Concordance (% Agreement):
- Target Not Detected:
§ 866.3183 Quantitative viral nucleic acid test for transplant patient management.
(a)
Identification. A quantitative viral nucleic acid test for transplant patient management is identified as a device intended for prescription use in the detection of viral pathogens by measurement of viral DNA or RNA using specified specimen processing, amplification, and detection instrumentation. The test is intended for use as an aid in the management of transplant patients with active viral infection or at risk for developing viral infections. The test results are intended to be interpreted by qualified healthcare professionals in conjunction with other relevant clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The labeling required under § 809.10(b) of this chapter must include:
(i) A prominent statement that the device is not intended for use as a donor screening test for the presence of viral nucleic acid in blood or blood products.
(ii) Limitations which must be updated to reflect current clinical practice. These limitations must include, but are not limited to, statements that indicate:
(A) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with clinical signs and symptoms and other relevant laboratory results; and
(B) Negative test results do not preclude viral infection or tissue invasive viral disease and that test results must not be the sole basis for patient management decisions.
(iii) A detailed explanation of the interpretation of results and acceptance criteria must be provided and include specific warnings regarding the potential for variability in viral load measurement when samples are measured by different devices. Warnings must include the following statement, where applicable: “Due to the potential for variability in [analyte] measurements across different [analyte] assays, it is recommended that the same device be used for the quantitation of [analyte] when managing individual patients.”
(iv) A detailed explanation of the principles of operation and procedures for assay performance.
(2) Design verification and validation must include the following:
(i) Detailed documentation of the device description, including all parts that make up the device, ancillary reagents required for use with the assay but not provided, an explanation of the methodology, design of the primer/probe sequences, rationale for the selected gene target, and specifications for amplicon size, guanine-cytosine content, and degree of nucleic acid sequence conservation. The design and nature of all primary, secondary and tertiary quantitation standards used for calibration must also be described.
(ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions;
(iii) Documentation and characterization (
e.g., determination of the identity, supplier, purity, and stability) of all critical reagents and protocols for maintaining product integrity throughout its labeled shelf-life.(iv) Stability data for reagents provided with the device and indicated specimen types, in addition to the basis for the stability acceptance criteria at all time points chosen across the spectrum of the device's indicated life cycle, which must include a time point at the end of shelf life.
(v) All stability protocols, including acceptance criteria.
(vi) Final lot release criteria along with documentation of an appropriate justification that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims.
(vii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Mode Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel viral stains (
e.g., regular review of published literature and annual in silico analysis of target sequences to detect possible primer or probe mismatches). All results of this protocol, including any findings, must be documented.(viii) Analytical performance testing that includes:
(A) Detailed documentation of the following analytical performance studies: limit of detection, upper and lower limits of quantitation, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, quality control, specimen stability studies, and additional studies as applicable to specimen type and intended use for the device;
(B) Identification of the viral strains selected for use in analytical studies, which must be representative of clinically relevant circulating strains;
(C) Inclusivity study results obtained with a variety of viral genotypes as applicable to the specific assay target and supplemented by in silico analysis;
(D) Reproducibility studies that include the testing of three independent production lots;
(E) Documentation of calibration to a reference standard that FDA has determined is appropriate for the quantification of viral DNA or RNA (
e.g., a recognized consensus standard); and(F) Documentation of traceability performed each time a new lot of the standardized reference material to which the device is traceable is released, or when the field transitions to a new standardized reference material.
(ix) Clinical performance testing that includes:
(A) Detailed documentation from either a method comparison study with a comparator that FDA has determined is appropriate, or results from a prospective clinical study demonstrating clinical validity of the device;
(B) Data from patient samples, with an acceptable number of the virus-positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision points. If an acceptable number of virus-positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision cannot be obtained, contrived samples may be used to supplement sample numbers when appropriate, as determined by FDA;
(C) The method comparison study must include predefined maximum acceptable differences between the test and comparator method across all primary outcome measures in the clinical study protocol; and
(D) The final release test results for each lot used in the clinical study.
0
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January 29, 2021
Roche Molecular Systems, Inc. Raji Grewal Sr. Regulatory Specialist 4300 Hacienda Drive Pleasanton, California 94588-2722
Re: K203220
Trade/Device Name: cobas BKV Regulation Number: 21 CFR 866.3183 Regulation Name: Ouantitative Viral Nucleic Acid Test for Transplant Patient Management Regulatory Class: Class II Product Code: QLX Dated: October 30, 2020 Received: November 2, 2020
Dear Raji Grewal:
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,
Maria Garcia, Ph.D. Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K203220
Device Name cobas® BKV
Indications for Use (Describe)
cobas® BKV is an in vitro nucleic acid amplification test for the quantitation of BKV) DNA in human EDTA plasma and urine stabilized in cobas® PCR media on the cobas® 6800/8800 Systems.
In EDTA plasma, cobas® BKV is intended for use as an aid in the management of BKV in transplant patients. In patients undergoing monitoring of BKV in EDTA plasma, serial DNA measurements can be used to indicate the need for potential treatment changes and to assess viral response to treatment.
In urine stabilized in cobas® PCR Media, cobas® BKV is intended for use as an aid in the management of BKV in transplant patients.
The results from cobas® BKV are intended to be read and analyzed by a qualified licensed healthcare professional in conjunction with clinical signs and symptoms and relevant laboratory findings. Test results must not be the sole basis for patient management decisions .
cobas® BKV is not intended for use as a screening test for blood products or human cells, tissues, and cellular and tissue-based products (HCT/Ps).
| 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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cobas® BKV 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Submitter Name | Roche Molecular Systems, Inc. |
|---|---|
| Address | 4300 Hacienda Drive |
| Pleasanton, CA 94588-2722 | |
| Contact | Raji Grewal |
| Phone: (925) 368-0246 | |
| FAX: (925) 225-0207 | |
| Email: raji.grewal@roche.com | |
| Date Prepared | October 30, 2020 |
| Proprietary Name | cobas® BKV |
| for use on cobas® 6800/8800 Systems | |
| Classification Name | Quantitative viral nucleic acid test for transplant patient management |
| Product Codes | QLX: 21 CFR 866.3183 |
| Predicate Devices | cobas® BKV (K202215) |
| Establishment Registration | Roche Molecular Systems, Inc. (2243471) |
DEVICE DESCRIPTION 1.
cobas® BKV (Figure 1) is based on fully automated sample preparation (nucleic acid extraction and purification) followed by PCR amplification and detection. The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software which assigns test results for all tests as either target not detected, BKV DNA detected ULoQ (upper limit of quantitation), or a value in the linear range LLoQ 3.9 | Total |
|-----------------------------|-----------------------------------------------------|--------------------------------------------|----------------------------------------|--------------|--------------------------------------------------------------------------|--------------------|-------|
| Target Not
Detected | 62 | 6 | 0 | 0 | 0 | 0 | ୧୫ |
| 3.9 | Total |
|-----------------------------|-----------------------------------------------------|--------------------------------------------|----------------------------------------|----------------------------------------|--------------------------------------|---------------------------------|-------|
| 3.3 to 3.9 | 0 | 0 | 0 | 2 | 8 | 169 | 179 |
| Total | 66 | 30 | 8 | 16 | 18 | 170 | 308 |
| Column Agreement
(%) | (66/66)
100.0% | (30/30)
100.0% | (6/8)
75.0% | (14/16)
87.5% | (18/18)
100.0% | (169/170)
99.4% | - |
| (95% Score CI)a | (94.5%,
100.0%) | (88.6%,
100.0%) | (40.9%,
92.9%) | (64.0%,
96.5%) | (82.4%,
100.0%) | (96.7%,
99.9%) | - |
Note: CI = Confidence Interval; LLoQ = lower limit of quantitation; LDT = laboratory developed test; BKV = BK virus.
Standard Deviation of Comparator BKV LDT estimated at 0.15 log10 U/mL (comparator BKV LDT validation study). Analyte concentration of 3.3 log10 IU/mL represented LLoQ + 2σ, 3.6 log10 IU/mL represented LLoQ + 4σ and 3.9 log10 IU/mL represented LLoQ + 60 with a range interval of 20.
Paired samples evaluable for clinical concordance analysis were included in this table.
ªAssumed independence between all samples.
DNA sequencing performed on representative samples from subjects with results consistently offset by more than 1 logio IU/mL DNA level did not reveal any sequence mismatches for any primer or probe targets for cobas® BKV.
Discordant results were defined as those that are more than one box away from the diagonal (indicated by shading). For Target Not Detected (TND) by LDT Column Agreement the cobas® BKV Target Not Detected and