(669 days)
Not Found
No
The document describes a standard in vitro diagnostic assay measuring a specific biomarker (TKa) and its correlation with disease progression based on a fixed cut-off value. There is no mention of AI, ML, or any learning algorithms used in the device's operation or interpretation of results. The performance studies focus on analytical and clinical validation using traditional statistical methods (sensitivity, specificity, ROC analysis) and do not describe training or testing of an AI/ML model.
No.
This device is an in vitro diagnostic device intended for measuring thymidine kinase activity (TKa) in human serum to aid in monitoring disease progression. It does not directly treat or cure a disease or condition.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states, "DiviTumTKa is an in vitro diagnostic device intended for the semi-quantitative measurement of thymidine kinase activity (TKa) in human serum."
No
The device is an in vitro diagnostic kit containing reagents and a reaction plate, which are physical components, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "DiviTumTKa is an in vitro diagnostic device intended for the semi-quantitative measurement of thymidine kinase activity (TKa) in human serum."
This statement directly identifies the device as an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
DiviTumTKa is an in vitro diagnostic device intended for the semi-quantitative measurement of thymidine kinase activity (TKa) in human serum. The assay is to be used as an aid in monitoring disease progression in previously diagnosed hormone receptor positive, metastatic postmenopausal female breast cancer patients. A TKa value of 21 days) sampling.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision/Reproducibility: A precision evaluation study was designed in accordance with CLSI guideline EP05-A3, testing reproducibility, repeatability, and sources of variation for assay: Operator, reagent lot and laboratory site. The study was divided into four parts: Two single site studies, a multi-site study and a lot-to-lot study.
The 1st single site precision evaluation study was performed at one site with five samples in five replicates per assay run, by two operators for 10 days per operator, and with three kit lots. The 2nd single site precision evaluation study was performed with six samples in two replicates per assay run for 20 days with two assay runs per day. The study was conducted by two operators at one site. The multisite precision evaluation study was conducted at three individual study sites (of which two are external CLIA certified laboratories) with five samples in five replicates per assay run for five days per site for a total of fifteen days. The lot-to-lot precision evaluation study was performed at one site by two operators using 3 unique (regarding critical raw materials) kit lots. Three kit lots were assayed per day for 5 days. The study was conducted with 5 replicates per run and per kit lot. All studies fulfilled pre-defined acceptance criteria.
Linearity/Assay Reportable Range: The assay linearity interval was defined as 100 – 2000 DuA. Sample pools “HIGH” and “LOW” were prepared using native serum samples. Measured values were plotted against expected values, and Weighted least squares (WLS) linear regression analysis applied. The results showed a curve described by the equation: Measured value = 4.157 + 0.96 x Expected value, with an R2 of 0.996.
High Dose Hook Effect: A dilution linearity test was performed in accordance with CLSI guideline EP34 1st edition. No Hook effect was observed within a TK-concentration range that reaches up to approximately 100,000 DuA.
Detection Limit:
Limit of Blank (LOB): 33 DuA.
Limit of Detection (LOD): 47 DuA.
Limit of Quantitation (LOQ): The estimated LoQ of DiviTum®TKa is 80 DuA.
Analytical Measuring Interval (AMI): 100 DuA to 2000 DuA. Samples below 100 DuA will be reported as 2000 DuA.
Analytical Specificity: The effects of 55 potential interfering substances were tested. None showed significant interference when tested within normal reference values. Interference was observed for serum samples with high lipemia (>427 mg/dl) or with abnormally elevated Bilirubin (≥18 mg/dL) or using Cisplatin or with abnormally elevated ALP levels (>980 U/l).
Clinical Studies: A clinical validation study was conducted with 454 patients (total of 1598 DiviTum®TKa serum samples/test results, 1546 included in analysis after exclusions). From 1164 DiviTum®TKa monitoring tests (during treatment), disease progression within 30 days from testing was seen in 63 cases. 33 (52.4%) of these 63 samples with disease progression had TKa ≥ 250 DuA. 888 (80.7%) of 1101 samples with TKa
§ 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.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. FOOD & DRUG ADMINISTRATION" stacked on top of each other.
July 29, 2022
Biovica International AB Joakim Arwidson Regulatory and QA Director Dag Hammarskjölds väg 54B Uppsala, 75237 Sweden
Re: K202852
Trade/Device Name: DiviTumTKa Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: QTE Dated: April 28, 2022 Received: May 2, 2022
Dear Joakim Arwidson:
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
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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,
Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics 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) K202852
Device Name DiviTum®TKa
Indications for Use (Describe)
DiviTumTKa is an in vitro diagnostic device intended for the semi-quantitative measurement of thymidine kinase activity (TKa) in human serum. The assay is to be used as an aid in monitoring disease progression in previously diagnosed hormone receptor positive, metastatic postmenopausal female breast cancer patients. A TKa value of Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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Traditional 510(k) Submission. DiviTum®TKa A.6 510(k) Summary DiviTum®TKa 510(K) OWNER: Biovica International AB ADDRESS: Dag Hammarskjölds Väg 54B, 752 37 Uppsala, Sweden PHONE NUMBER: + 46 (0) 18 44 44 830 EMAIL: info@biovica.com NAME OF CONTACT PERSON: Joakim Arwidson DATE THE SUMMARY WAS PREPARED: April 7th, 2021
A. 510(K) Number
PURPOSE OF SUBMISSION B.
New Device
C. MEASURAND
Thymidine Kinase Activity (TKa)
D. TYPE OF TEST
Semiquantitative, enzyme immunoassay
E. APPLICANT
Biovica International AB
F. PROPRIETARY AND ESTABLISHED NAMES
DiviTum®TKa DiviTum®
G. REGULATORY INFORMATION
Regulation Section 21 CFR §866.6010, Tumor - Associated antigen immunological test system
Classification Class II
Product Code QTE
Panel Immunology (82) (Assay) Clinical Chemistry (75) (Calibrators and Controls)
H. INTENDED USE
1. Intended Use(s)
DiviTumTKa is an in vitro diagnostic device intended for the semi-quantitative measurement of thymidine kinase activity (TKa) in human serum. The assay is to be used as an aid in monitoring disease progression in previously diagnosed hormone receptor positive, metastatic postmenopausal female breast cancer patients. A TKa value of 2000 DuA.
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Traditional 510(k) Submission, DiviTum®TKa A.6 510(k) Summary DiviTum®TKa
Analytical Specificity l.
The effects of 55 potential interfering substances (Table 7) were tested according to the CLSI guidelines EP07 3rd edition and EP37 1* edition. When tested within normal reference values, none of the 55 tested substances showed any significant interference with DiviTum®TKa. However, interference was observed for serum samples with high lipemia (>427 mg/dl) or with abnormally elevated Bilirubin (at ≥18 mg/dL) or using Cisplatin or with abnormally elevated ALP levels (>980 U/l), the DiviTum®TKa results shall be interpreted with caution.
| Table 7. List of the 52 tested substances not interfering with DiviTum®TKa | ||||
|---|---|---|---|---|
Exogenous substances
| 5-fluorouracil |
|---|
| Abemaciclib |
| Acetylcysteine |
| Acetylsalycilic acid |
| Aminoglutethimidine |
| Ampicillin-Na |
| Anastrozole |
| Ascorbic acid |
| Brivudine |
| Capecitabine |
| Carboplatin |
| Cyclophosphamide |
| Cyclosporine |
| Docetaxel |
| Doxorubicin |
| Doxycycline |
| Epirubicin |
| Eribulin |
| Everolimus |
| Exemestane |
| Foscarnet |
| Fulvestrant |
| Goserelin |
| Heparin |
| Ibuprofen |
| Lapatinib |
| Letrozole |
| Leuoprorelin |
| Levodopa |
| Loperamid |
| Megestrol Acetate |
| Methotrexate |
| Metoklopramid |
| Metronidazole |
| Mitomycin C |
| Morphine |
| Omeprazole |
| Paclitaxel |
| Palbociclib |
| Paracetamol |
| Ribociclib |
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Traditional 510(k) Submission. DiviTum®TKa A.6 510(k) Summary DiviTum®TKa Tamoxifen Theophylline Toremifene Trastuzumab Zidovudine Endogenous substances Hemoglobin Bilirubin, unconjugated Albumin and y-globulin Alkaline phosphatase HAMA
RF
f. Clinical reference value ("cut-off") See clinical reference value below.
2. COMPARISON STUDIES
- Method comparison with predicate device a. Not applicable. The predicate measures a different analyte. Extensive analytical and clinical studies are presented to demonstrate a high safety and efficacy profile.
- Matrix comparison b. Not applicable. Serum samples are the only matrix used for analysis.
3. CLINICAL STUDIES
The effectiveness of the DiviTum®TKa as an aid in monitoring disease progression in previously diagnosed postmenopausal HR+ metastatic breast cancer patients undergoing treatment, was determined through a clinical validation study using left-over banked serum samples from metastatic breast cancer patients undergoing treatment. Multiple time-point measurements of TKa in serum samples from patients were linked to clinical data on disease progression. The clinical validation study included 454 patients (subjects) with a total of 1598 DiviTum®TKa serum samples/test results. 52 serum samples/test results obtained after the patient had progressed were excluded before the statistical analysis. These 52 serum samples were distributed over the 454 patients. The number of serum samples/test results - included in all the statistical analyses, and still representing 454 patients, hence constituted 1546 test results of which 1164 test results (samples) were captured during treatment, but still representing all 454 patients. The remaining 382 test results (samples) were from baseline (i.e., pre-treatment). The multiple time-point test results were divided into time intervals based on the original sampling day (phlebotomy) - i.e., actual visit (sampling) day at physician after registration. Patient treatment was initiated according to patient information - i.e., after baseline (>21 days) sampling.
The number of DiviTum®TKa measurements per patient (N=454) and TKa mean, median, minimum, and maximum values per time interval are listed in Table 6.
Table 6 - Number of Divilland TKa measurements (N=454) and TKa mean, median, minimum, and massiman values per time internal
| Variable | Statistic | Patients
(%) |
|-------------------------------------------|-------------|-----------------|
| Number of TKa measurements per
patient | 1
n1 (%) | 55 (12.1%) |
| | 2
n2 (%) | 50 (11.0%) |
| | 3
n3 (%) | 100 (22.0%) |
| | 4
n4 (%) | 102 (22.4%) |
| | 5
n5 (%) | 147 (32.3%) |
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Traditional 510(k) Submission. DiviTum®TKa A.6 510(k) Summary DiviTum®TKa
| Measurement (DuA) | ||
|---|---|---|
| TKa baseline (154 days; cycle 7) | Mean (SD) | 243 (966) |
| Median | 142 | |
| Min; Max | 25; 14 674 |
Elevated serum TKa was defined as above or equal to 250 DuA (clinical reference value).
From the 1164 DiviTum®TKa monitoring tests (during treatment), disease progression within 30 days from testing was seen in 63 cases. Thirty-three (52.4%) of the 63 samples with disease progression had TKa above the clinical reference value (≥250 DuA). Eight hundred and eightyeight (80.7%) of the 1101 samples with TKa