(76 days)
The Tina-quant Cystatin C Gen.2 is an in vitro test for the quantitative determination of cystatin C in human serum and plasma on Roche/Hitachi cobas c systems. Cystatin C measurements are used as an aid in the diagnosis and treatment of renal diseases.
Calibrator:
The C.f.a.s. (Calibrator for automated systems) Cystain C is for use in the calibration of quantitative Roche methods on Roche clinical chemistry analyzers as specified in the value sheets.
Control:
The Cystatin C Control Set Gen.2 is for use in quality control by monitoring accuracy and precision for the quantitative methods as specified in the value sheets.
Roche Tina-quant Cystatin C Gen. 2 reagent provides quantitative measurement of the cystatin C that is present in human serum and plasma. Assay: Reagents are packaged in a cassette with two bottles labeled with their instrument positioning, R1 (Reagent 1) and R2 (Reagent 2). R I contains solution of polymers in MOPS-buffered saline; preservative, stabilizers. R2 is latex particles in glycine buffer coated with anti-Cystatin C antibodies (rabbit); preservative, stabilizers.
Calibrator:
C.f.a.s. Cystatin C is a liquid, ready-to-use calibrator based on pooled delipidated human serum enriched with recombinant human Cystatin C produced in E. Coli. Single level calibrators with lot specific values are diluted on board the analyzer to create a 6-point calibration curve.
Control:
Cystatin C Control Set contains 3 controls based on pooled delipidated human serum enriched with human recombinant Cystatin C produced in E. Coli.
The provided text describes the analytical performance of the Tina-quant Cystatin C Gen. 2 test system. Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
| Test Parameter | Acceptance Criteria (from text) | Reported Device Performance |
|---|---|---|
| Precision (Repeatability) | Not explicitly stated as a single "acceptance criteria" but implied by the provided data. | Within Run Imprecision (CV%)- Control 1 (1.00 mg/L): 1.7%- Control 2 (1.84 mg/L): 0.9%- Control 3 (4.12 mg/L): 0.7%- Human Serum 1 (0.560 mg/L): 1.8%- Human Serum 2 (2.80 mg/L): 0.6%- Human Serum 3 (6.39 mg/L): 0.6% |
| Precision (Intermediate Precision) | Not explicitly stated as a single "acceptance criteria" but implied by the provided data. | Total Imprecision (CV%)- Control 1 (1.00 mg/L): 2.2%- Control 2 (1.84 mg/L): 1.4%- Control 3 (4.12 mg/L): 1.4%- Human Serum 1 (0.560 mg/L): 2.0%- Human Serum 2 (2.80 mg/L): 1.3%- Human Serum 3 (6.39 mg/L): 1.1% |
| Linearity (Serum) | Reported R² value close to 1 for linear regression. | R² = 0.999 (for Y = 1.001x - 0.0057) |
| Linearity (Plasma) | Reported R² value close to 1 for linear regression. | R² = 0.999 (for Y = 1.000x + 0.0000) |
| Lower Limit of Blank (LoB) | LoB claim = 0.30 mg/L | 0.30 mg/L (as the claim) |
| Lower Limit of Detection (LoD) | LoD claim = 0.40 mg/L | 0.40 mg/L (as the claim) |
| Lower Limit of Quantitation (LoQ) | LoQ claim = 0.40 mg/L at % CV of 13.3 | 0.40 mg/L at % CV of 13.3 (as the claim) |
| Endogenous Interference (Hemoglobin, Lipemia, Bilirubin, Rheumatoid Factor) | Recovery within ± 0.100 mg/L of initial values for samples ≤ 1.00 mg/L and within ± 10% for samples > 1.00 mg/L. | All data passed the acceptance criteria; specific interferent limits provided (e.g., Lipemia up to 1000 L index, Hemolysis up to 1000 H index, Bilirubin up to 60 I index, Rheumatoid factor < 1200 IU/mL). |
| Common Drug Interference | Difference in recovery to the reference sample: ≤ ± 10% | All data passed the acceptance criteria; specific drug concentrations shown not to interfere were listed. |
| Method Comparison (Candidate vs. Predicate) | Not explicitly stated as a numerical range, but implied to show substantial equivalence. | Passing/Bablok: Y = 0.997x - 0.064 mg/L, T = 0.937.Linear Regression: y = 1.031x - 0.153 mg/L, r = 0.988. |
| Matrix Comparison (Plasma vs. Serum) | For sample concentrations ≤ 0.1 mg/L, the deviation must be ≤ ± 10 mg/L. For sample concentrations > 0.1 mg/L, the deviation must be ≤ ± 10%. | All data passed the acceptance criteria; specific P/B equations provided (e.g., Serum vs. Li-heparin: y = 1.010x + 0.020, r = 1.000). |
2. Sample Size Used for the Test Set and Data Provenance
- Precision and Reproducibility:
- Test Set: Three human serum samples (0.56, 2.80, and 6.39 mg/L) and three control samples. Each sample was tested in two aliquots per run, two runs per day for 21 days.
- Data Provenance: Not explicitly stated, but clinical studies are generally performed in a controlled laboratory environment. The context implies it's internal study data.
- Linearity/Assay Reportable Range:
- Test Set: One batch of reagent, samples measured in triplicate. Two separate dilution series: plasma (thirteen levels) and serum (twenty-one levels).
- Data Provenance: Not explicitly stated, but internal study data.
- Detection Limit (LoB, LoD, LoQ):
- Test Set:
- LoB: One blank sample tested n=5 with two analyzers and three reagent batches for six runs per day across three days.
- LoD: Five low-analyte samples measured in singlicate on two analyzers with three reagent batches for six runs per day across three days.
- LoQ: A low-level sample set (prepared by diluting 5 human serum samples) tested in 2 replicates per sample on 5 days, one run per day on one cobas c 501 analyzer.
- Data Provenance: Not explicitly stated, but internal study data.
- Test Set:
- Analytical Specificity (Endogenous Interference):
- Test Set: One pool of human serum spiked with interferent vs. a second pool without, mixed in different ratios to create a dilution series. Tested at two levels of Cystatin C.
- Data Provenance: Not explicitly stated, but internal study data.
- Analytical Specificity (Common Drug Interference):
- Test Set: Two sample pools (low and high Cystatin C) divided into aliquots. One aliquot served as reference; others spiked with drugs. Samples determined in triplicate.
- Data Provenance: Not explicitly stated, but internal study data.
- Method Comparison with Predicate Device:
- Test Set: 103 human serum samples.
- Data Provenance: Not explicitly stated as retrospective or prospective, but likely prospective for the comparison study. The country of origin is not specified.
- Matrix Comparison:
- Test Set: 57 tubes collected per anticoagulant (Li-heparin, K2-EDTA, K3-EDTA, Gel Separation Tube).
- Data Provenance: Internal study data.
- Expected Values/Reference Range:
- Test Set: n=273 subjects from a US panel of healthy subjects.
- Data Provenance: Prospective study from the US.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
Not applicable. This device is an in-vitro diagnostic test for quantitative determination of Cystatin C. The performance evaluation relies on laboratory measurements and statistical analysis against established analytical performance metrics, not expert interpretation of images or clinical cases for ground truth.
4. Adjudication Method for the Test Set
Not applicable, as the evaluation is based on quantitative measurements and statistical methods, not human interpretation that would require adjudication.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. The context describes an in-vitro diagnostic device, not an imaging or diagnostic aid that would typically involve human readers.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the studies described are standalone performance evaluations of the Tina-quant Cystatin C Gen. 2 test system. The device itself produces quantitative measurements without human-in-the-loop performance influencing the measurement output. The studies evaluate the analytical performance of the system directly.
7. The Type of Ground Truth Used
The "ground truth" for the performance studies is the reference method or expected/true concentration of Cystatin C.
- For precision, it's the statistical variability around the measured mean.
- For linearity, it's the expected linear relationship between serially diluted samples and their measured concentrations.
- For detection limits, it's the inherent chemical/physical limits of the assay.
- For interference studies, it's the known concentration of the analyte without the interferent, and the known concentration of the interferent itself.
- For method comparison, the predicate device's results serve as a comparative "truth" to establish substantial equivalence.
- For matrix comparison, serum results are compared as a baseline for other plasma types.
- For expected values, the ground truth is the statistically derived reference interval from a healthy population.
- For traceability, the device is standardized against the ERM-DA471/IFCC reference material, which acts as the ultimate "ground truth" for Cystatin C measurement.
8. The Sample Size for the Training Set
This information is not provided in the document. The studies described are performance validation studies, not directly describing a machine learning algorithm's "training set." If the device uses an internal algorithm (not specified if it's a machine learning algorithm), the training set for that algorithm is not detailed.
9. How the Ground Truth for the Training Set was Established
This information is not provided in the document. As mentioned above, the document details analytical performance studies rather than the development of a machine learning model's training which would require ground truth establishment for a training set.
{0}------------------------------------------------
- � '
JUL | 7 2014 510(k) Summary for Tina-quant Cystatin C Test System, Calibrator and Control Set
| Date prepared: | July 14th, 2014 |
|---|---|
| Purpose of submission | Roche Diagnostics hereby submits this 510(k) to provide FDA with notification of intent to market a new device named Tina-quant Cystatin C Gen. 2 reagent. This candidate device is a new reagent that was developed by Roche Diagnostics. The Diazyme Cystatin C Assay was cleared in 510(k) K093680 and serves as the predicate device. The candidate reagent uses the same calibrator that was cleared in K080811 and the new Cystatin C Control Set. The new Control Set Gen.2 has three levels compared to the two levels control set which previous cleared in K080811. The Mid level is the only difference between this control set and the one that was cleared in K080811. This submission presents data to support clearance of this new reagent and control. All data in this submission was generated on the cobas c 501 analyzer. |
| Measurand | Cystatin C |
| Type of test | Quantitative turbidimetric method |
| Applicant | Mr. Khoa TranRoche Diagnostics9115 Hague RoadIndianapolis, IN 46250Telephone: (317) 521-3409Fax: (317) 521-2324Email: khoa.tran@roche.com |
| Candidate device names | Proprietary name:cobas c Tina-quant Cystatin C Gen. 2Common name:Cystatin C Gen. 2 |
{1}------------------------------------------------
510(k) Summary for Tina-quant Cystatin C Test System, Calibrator and Control Set, Continued
Regulatory information
| Product Code | Classification | Regulation | Panel |
|---|---|---|---|
| NDY | Class II | 21 CFR 862.1225(Cystatin C test system) | ClinicalChemistry |
| JIT | Class II | 21 CFR 862.1150,(Calibrator, secondary) | ClinicalChemistry |
| JJX | Class I | 21 CFR 862.1660, (Single(specified) analyte controls(assayed and unassayed)) | ClinicalChemistry |
{2}------------------------------------------------
510(k) Summary for Tina-quant Cystatin C Test System, Calibrator and Control Set, Continued ______________________________________________________________________________________________________________________________________________________________________________
Intended use In vitro test for the quantitative determination of cystatin C in human serum and plasma on Roche/Hitachi cobas e systems. Indications for Tina-quant Cystatin C Gen. 2 assay: The Tina-quant Cystatin C Gen. 2 is an in vitro test for the quantitative use determination of cystatin C in human serum and plasma on Roche/Hitachi cobas c systems. Cystatin C measurements are used as an aid in the diagnosis and treatment of renal diseases. C.f.a.s. Cystatin C: The C.f.a.s. Cystatin C is for use in the calibration of quantitative Roche methods on Roche clinical chemistry analyzers as specified in the value sheets. Cystatin C Control Set Gen.2: The Cystatin C Control Set is for use in quality control by monitoring accuracy and precision for the quantitative methods as specified in the value sheets. Special For prescription use only conditions for use Special For use on Roche/Hitachi cobas c systems instrument requirements Roche Tina-quant Cystatin C Gen. 2 reagent provides quantitative Candidate device measurement of the cystatin C that is present in human serum and plasma. description Assay: Reagents are packaged in a cassette with two bottles labeled with their instrument positioning, R1 (Reagent 1) and R2 (Reagent 2). R I contains solution of polymers in MOPS-buffered saline; preservative, stabilizers. R2 is latex particles in glycine buffer coated with anti-Cystatin C antibodies (rabbit); preservative, stabilizers.
{3}------------------------------------------------
Calibrator:
C.f.a.s. Cystatin C is a liquid, ready-to-use calibrator based on pooled delipidated human serum enriched with recombinant human Cystatin C produced in E. Coli. Single level calibrators with lot specific values are diluted on board the analyzer to create a 6-point calibration curve.
Control:
Cystatin C Control Set contains 3 controls based on pooled delipidated human serum enriched with human recombinant Cystatin C produced in E. Coli.
Predicate device
Diazyme Cystatin C Assay was cleared in K093680 on the Hitachi 917 analyzer for the quantitative determination of Cystatin C in serum or plasma by latex enhanced immunoturbidimetric method. The measurement of Cystatin C is used as an aid in the diagnosis and treatment of renal disease. C.f.a.s Cystatin C calibrator and Cystatin C Control Set were cleared in K080811 on Hitachi 917, MODULAR P, cobas c 501.
{4}------------------------------------------------
510(k) Summary for Tina-quant Cystatin C Test System, Calibrator and Control Set, Continued
The following table compares the identical features of the candidate device to Substantial equivalence the predicate device that was cleared in 510(k) K093680 and K080811. similarities
| Feature | Predicate Device:Diazyme Cystatin C | Candidate Device:Tina-Quant Cystatin C Gen.2 |
|---|---|---|
| Intended Use | The Diazyme Cystatin C Assay is anin-vitro diagnostic test for thequantitative determination ofCystatin C in serum or plasma bylatex enhanced immunoturbidimetricmethod. The measurement ofCystatin C is used as an aid in thediagnosis and treatment of renaldisease. | The Tina-Quant Cystatin CGen.2 is an in vitro test for thequantitative determination ofCystatin C in human serumand lithium-heparin plasmaon Roche automated clinicalchemistry analyzers. CystatinC measurements are used asan aid in the diagnosis andtreatment of renal diseases. |
| Sample Types | Serum and plasma | Same |
| PermissibleAnticoagulants | Li-heparin plasmaK2-EDTA plasma | Li-heparin plasmaK2-EDTA, K3-EDTA plasma |
| Reference Method | colorimetric method | Same |
| Calibrator | 5 Levels Cystatin C Calibrators andsaline as the zero calibrator. | C.f.a.s. (Calibrator forautomated systems), singlelevel and use water as the zerocalibrator.(C.f.a.s. cleared for use withCystatin C assay in 510(k)K080811) |
| Calibration Stability | Any calibration frequency isdependent on instrument used.Additionally, that assay should berecalibrated and controls run witheach new lot of reagent. | After reagent lot change andas required following qualitycontrol procedures. |
| Reagent Shelf LifeStability | Unopened: 2-8 °C until expirationdateOn-board in use:4 weeks | Unopened: 2-8 °C untilexpiration dateOn-board in use:8 weeks |
| Calibration Mode | 6-point: Spine | Same |
{5}------------------------------------------------
| Traceability | Standardized against the Doumas manual reference method | Assay: This method has been standardized against ERM-DA471/IFCC reference material.Calibrator: The Cystatin C calibrator is traceable to ERM-DA471/IFCC reference material. The value assignment was carried out by turbidimetry on Hitachi 917 analyzer.Control: The Cystatin C control is traceable to ERM-DA471/IFCC reference material. The value assignment was carried out by turbidimetry on Hitachi 917 analyzer. |
|---|---|---|
| Instrument Platform | Hitachi 917 analyzer | cobas c 501 analyzer |
.
Continued on next page
.
{6}------------------------------------------------
The following table compares the different features of the candidate device to Substantial equivalence the predicate device that was cleared in 510(k) K093680 and K080811. differences
| Feature | Predicate Device:Diazyme Cystatin C | Candidate Device:Tina-Quant Cystatin C Gen. 2 |
|---|---|---|
| Reagent Composition | R1:100 mM Tris-buffer SolutionR2:Suspension of anti-human Cystatin C chicken polyclonal antibody coated latex particles (< 0.5%). | R1:Solution of polymers in MOPS-buffered saline; preservative, stabilizersR2:Latex particles in glycine buffer coated with anti-Cystatin C antibodies (rabbit); preservative, stabilizers |
| Reagent On-Board Stability | on-board in use and refrigerated on the analyzers: 4 weeks | on-board in use and refrigerated on the analyzers: 8 weeks |
| Controls | Cystatin C Control | Cystatin C Control Set (3 levels)These two level control set was cleared for use with Cystatin C in K080811. |
{7}------------------------------------------------
510(k) Summary for Tina-quant Cystatin C Test System, Calibrator and Control Set, Continued and the same of the same of the same of the same of the same of the same of
Substantial equivalence - differences continued
| Feature | Predicate Device:Diazyme Cystatin C | Candidate Device:Tina-Quant Cystatin C Gen. 2 |
|---|---|---|
| Measuring Range | 0.2 - 8.0 mg/L | 0.40 - 6.80 mg/L |
| Expected Values | Age 18-550.62-1.16 mg/L | Age 21-770.61-0.95 mg/L |
| Hook Effect | Not tested | No hook effect up to 20 mg/L |
| Lower Limits ofMeasurement | LoB: 0.04 mg/LLoD: 0.07 mg/LLoQ: 0.19 mg/L | LoB: 0.30 mg/LLoD: 0.40 mg/LLoQ: 0.40 mg/L |
{8}------------------------------------------------
| Test principle | Tina-quant Cystatin C Gen.2 measures cystatin C in human serum and plasmaon Roche automated clinical analyzer by turbidimetric method. The humancystatin C agglutinates with latex particles coated with anti-cystatin Cantibodies. The aggregate is determined turbidimetrically at 546 nm. |
|---|---|
| Precision/reproducibility | Precision was determined according to CLSI EP5-A2. The study includedthree human serum samples (0.56, 2.80, and 6.39 mg/L) and three control |
three human serum samples (0.56, 2.80, and 6.39 mg/L) and three control samples in two aliquots per run and two runs per day for 21 days.
Here are summaries of the repeatability and intermediate precision data.
| Repeatability Summary | ||||||
|---|---|---|---|---|---|---|
| Human | Human | Human | ||||
| Specimen | Control 1 | Control 2 | Control 3 | Serum 1 | Serum 2 | Serum |
| Total Mean (mg/L) | 1.00 | 1.84 | 4.12 | 0.560 | 2.80 | 6.39 |
| Within Run ImprecisionSD (mg/L) | 0.02 | 0.02 | 0.03 | 0.010 | 0.02 | 0.04 |
| Within Run ImprecisionCV% | 1.7 | 0.9 | 0.7 | 1.8 | 0.6 | 0.6 |
| Min (mg/L) | 0.88 | 1.76 | 4.01 | 0.530 | 2.73 | 6.25 |
| Max (mg/L) | 1.04 | 1.89 | 4.22 | 0.590 | 2.88 | 6.55 |
Intermediate Precision
| mediate Precision | ||||||
|---|---|---|---|---|---|---|
| Human | Human | Human | ||||
| Specimen | Control 1 | Control 2 | Control 3 | Serum 1 | Serum 2 | Serum 3 |
| Total Mean (mg/L) | 1.00 | 1.84 | 4.12 | 0.560 | 2.80 | 6.39 |
| Total ImprecisionSD (mg/L) | 0.02 | 0.03 | 0.06 | 0.011 | 0.04 | 0.07 |
| Total ImprecisionCV% | 2.2 | 1.4 | 1.4 | 2.0 | 1.3 | 1.1 |
| Min (mg/L) | 0.88 | 1.76 | 4.01 | 0.530 | 2.73 | 6.25 |
| Max (mg/L) | 1.04 | 1.89 | 4.22 | 0.590 | 2.88 | 6.55 |
Values that appear in bold type also appear in the labeling.
{9}------------------------------------------------
Linearity/ assay Linearity was assessed according to CLSI EP6-A with one batch of reagent. reportable in one run, and with samples measured in triplicate. Two separate dilution range series differing by sample type (serum and plasma) were prepared with thirteen levels for the plasma series and twenty one levels for the serum series. Lithium-heparin was used to prepare the plasma sample series. The highest concentration samples exceed the desired measuring range. Human Serum sample pool with high concentration of Cystatin C, spiked with recombinant Cystatin C. Human Plasma sample pool with high concentration of Cystatin C, spiked with recombinant Cystatin C
Measuring Ranges that are Supported by the Linearity Data (mg/L)
| Plasma | Serum | |
|---|---|---|
| Range tested | 0.046 - 8.893 | 0.0 - 7.578 |
| Range found | 0.0 - 8.893 | 0.00 - 7.578 |
| Recommended measuring range | 0.40 - 6.80 | 0.40 - 6.80 |
The first order (linear) regression is significant for both sample types.
Linear Regression Equation for Serum Y = 1.001x - 0.0057 R2=0.999 Linear Regression Equation for Plasma Y = 1.000x + 0.0000 R2 =0.999
Traceability This method has been standardized against the ERM-DA471/IFCC reference and stability material.
The reagent has been evaluated for transport, shelf-life, and open on-board stability.
{10}------------------------------------------------
510(k) Summary for Tina-quant Cystatin C Test System, Calibrator and Control Set. Continued
Detection Limit LoB, LoD, and LoQ studies were performed based upon CLSI EP17-A2.
LoB Protocol: One blank sample was tested in n=5 with two analyzers with three reagent batches for six runs per day across three days.
LoD Protocol: Five low-analyte samples were measured in singlicate on two analyzers with three reagent batches for six runs per day across three days.
LoQ Protocol: A low Level Sample Set was prepared by diluting 5 human serum samples with an analyte free diluent (0.9% NaCl). The Low level Sample Set was tested in 2 replicates per sample on 5 days, one runs per day on one cobas c 501 analyzers. The mean concentration is plotted versus the % CV. The concentration at % CV of 13.3 is the LoQ.
The LoB, LoD, and LoQ claims represent the specifications for each.
LoB claim = 0.30 mg/L LoD claim = 0.40 mg/L LoQ claim = 0.40 mg/L at % CV of 13.3
{11}------------------------------------------------
Analytical specificity interference from endogenous substances
The reagent was evaluated with four endogenous substances, Hemoglobin, Lipemia, Bilirubin and Rheumatoid factor for potential interference with the measurement of Cystatin C.
One pool of human serum was spiked with the interferent. A second pool of human serum contained none. The two pools were mixed in different ratios to yield a dilution series with varying concentrations of the interferent.
The endogenous interference data are summarized in the table. Interference was tested at two levels of Cystatin C.
| no interference upto | Claim as it appears in thelabeling. | |
|---|---|---|
| Lipemia Level 1 | 2334 L index | No significant interference up |
| Lipemia Level 2 | 2364 L index | to an L index of 1000. |
| Hemolysis Level 1 | 1313 H index | No significant interference up |
| Hemolysis Level 2 | 1461 H index | to an H index of 1000. |
| Unconjugated BilirubinLevel 1 | 77 H index | No significant interference up |
| Unconjugated BilirubinLevel 2 | 73 H index | to an I index of 60. |
| Rheumatoid factor Level 1 | 1301 mg/L | Rheumatoid factor < 1200 |
| Rheumatoid factor Level 2 | 1216 mg/L | IU/mL do not interfere |
All data passed the following acceptance criteria:
Recovery within ± 0.100 mg/L of initial values for samples ≤ 1.00 mg/L and within ± 10% for sample > 1.00mg/L.
{12}------------------------------------------------
Analytical Seventeen commonly used drugs were examined for potential interference on specificity measurement with cobas c Tina-Quant Cystatin C Gen. 2 reagent. interference Two sample pools, containing a low and high concentration of Cystatin C are from common used. These sample pools are divided into an appropriate number of aliquots. drugs One aliquot is not spiked with the drugs and it is used as the reference sample for Cystatin C concentration. The Cystatin C concentration in the sample is determined with n = 3 measurements on a cobas c 501 analyzer.
The other sample aliquots, with either the high or low Cystatin C concentrations, are spiked with the respective amount of drug. The Cystatin C concentration of the spiked aliquots are determined in triplicate and the mean of the triplicate determinations is compared to the Cystatin C concentration determined for the reference aliquot (mean of n=3).
| Drug | Highest Concentration ShownNot to Interfere with Cystatin C(drug concentrations in mg/L) | |
|---|---|---|
| 1 | Acetylcystein | 150 |
| 2 | Ampicillin - Na | 1000 |
| 3 | Ascorbic acid | 300 |
| 4 | Cyclosporine | 5 |
| 5 | Cefoxitin | 2500 |
| 6 | Heparin | 5000U |
| 7 | Intralipid | 10000 |
| 8 | Levodopa | 20 |
| 9 | Methyldopa + 1.5 | 20 |
| 10 | Metronidazole | 200 |
| 11 | Phenylbutazone | 400 |
| 12 | Doxycyclin | 50 |
| 13 | Acetylsalycilic acid | 1000 |
| 14 | Rifampicin | 60 |
| 15 | Acetaminophen | 200 |
| 16 | Ibubrofen | 500 |
| 17 | Theophylline | 100 |
The table below summarizes the common drug interferences data:
All data passed the following acceptance criteria:
Difference in recovery to the reference sample: ≤± 10%
{13}------------------------------------------------
| Methodcomparisonwith predicatedevice | A total of 103 human serum samples were tested in singlicate with theCystatin C reagent from Diazyme on one Modular P and the CYSC2 reagenton one cobas c 501 analyzer.Cystatin C values for n=103 human sera adult samples were obtained usingthe candidate reagent (y-axis) to the predicate reagent (x-axis) on theRoche/Hitachi cobas c 501 analyzer. Candidate sample concentrationsranged from 0.500 to 6.67 mg/L, and they were tested in singlicate. Thevalues were regressed using the Passing/Bablok model to produce thefollowing equation. | |
|---|---|---|
| Passing/Bablok | Linear regression | |
| $Y = 0.997x - 0.064$ mg/L | $y = 1.031x - 0.153$ mg/L | |
| $T = 0.937$ | $r = 0.988$ |
and the same of the same of the same of the same of the same of
and the state of the state of the state of the state of the state of the states of the states of the states of the states of the states of the states of the states of the sta
{14}------------------------------------------------
Matrix comparison
Lithium-heparin, K2-EDTA and K3-EDTA are permissible anticoagulants for use with this reagent because they do not interfere with recovery of Cystatin C. In an internal study, a total of 57 tubes were collected per anticoagulant. Plasma results were compared to serum results and percent recovery was determined. In terms of % recovery. All data passed the following criteria: For sample concentrations ≤ 0.1 mg/L, the deviation must be ≤ ± 10 mg/L. For sample concentrations > 0.1 mg/L, the deviation must be ≤± 10%.
| anticoagulants | Sample concentrationrange tested (mg/L) | Claimed MeasuringRange (mg/L) |
|---|---|---|
| Li-Heparin (full) | 0.560 - 6.63 | |
| Li-Heparin (half) | 0.650 - 5.04 | |
| K2-EDTA (full) | 0.550 - 6.67 | 0.40 - 6.80 |
| K2-EDTA (half) | 0.630 - 5.05 | 0.40 - 6.80 |
| K3-EDTA (full) | 0.580 - 6.72 | 0.40 - 6.80 |
| K3-EDTA (half) | 0.620 - 4.89 | 0.40 - 6.80 |
| Gel Separation Tube | 0.510 - 6.55 | 0.40 - 6.80 |
In addition, method comparisons with plasma vs. serum were calculated with the following results:
| Serum vs. Li-heparin | P/B: y = 1.010x + 0.020, r = 1.000 |
|---|---|
| Serum vs. K2-EDTA | P/B: y = 1.020x - 0.010, r = 1.000 |
| Serum vs. K3-EDTA | P/B: y = 1.030x + 0.000, r= 1.000 |
| Serum vs. Gel Separation | P/B: y = 1.000x - 0.010, r = 1.000 |
Continued on next page
Page 15 of 16
{15}------------------------------------------------
です。そしても、そしてもない。
そしても、その後になっています。
「もっという」ということです。
「もっということです。」
「いない」ということです。」
「いない」ということです。」
「いない」ということです。」
「いない」ということです。」
「いない」ということです。」
「いない」ということです。」
「いない」ということです。」
「『
510(k) Summary for Tina-quant Cystatin C Test System, Calibrator and Control Set, Continued .
| Expectedvalues/reference range | Age 21-77 | 0.61 - 0.95 mg/L |
|---|---|---|
| Samples of subjects from US panel of healthy subjects were used as areference population (n=273) measured with Roche Tina-quant Cystatin CGen.2. They were evenly distributed across gender and age between 21 and77 years. | ||
| The analysis of the data with the 2.5% and the 97.5 % percentile gave aCystatin C range for from 0.61 mg/L to 0.95 mg/L. | ||
| Conclusion | The submitted information in this premarket notification supports asubstantial equivalence decision. |
{16}------------------------------------------------
Image /page/16/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, with three stylized wing-like shapes.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
July 17,2014
ROCHE DIAGNOSTICS KHOA TRAN REGULATORY AFFAIRS CONSULTANT 9115 HAGUE ROAD INDIANAPOLIS IN 46250-0416
Re: K141143
Trade/Device Name: Tina-quant Cystatin C Gen.2 Assay, C.f.a.s (Calibrator for automated systems) Cystatin C, Cystatin C Control Set Gen. 2 Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: II Product Code: NDY, JIT, JJX Dated: May 1, 2014 Received: May 2, 2014
Dear Mr. Khoa Tran:
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. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{17}------------------------------------------------
Page 2-Mr. Tran
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation cntitled. "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
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours, Katherine Serrano -5 For : Courtney H. Lias. Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics
and Radiological Health Center for Devices and Radiological Health
Enclosure
{18}------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.
510(k) Number (if known) K141143
Device Name
Tina-quant Cystatin C Gen.2 Assay, C.f.a.s (Calibrator for automated systems) Cystatin C Control Set Gen.2
Indications for Use (Describe)
The Tina-quant Cystatin C Gen.2 is an in vitro test for the quantitative determination of cystatin C in human serum and plasma on RochePlitachi cobas c systems. Cystatin C messurements are used as an aid in the diagnosis and treatment of renal diseases.
Calibrator:
The C.f.a.s. (Calibrator for automated systems) Cystain C is for use in the calibration of quantitative Roche methods on Roche clinical chemistry analyzers as specified in the value sheets.
Control:
The Cystatin C Control Set Gen.2 is for use in quality control by monitoring accuracy and precision for the quantitative methods as specified in the value sheets.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 807 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
14 11:14:
{19}------------------------------------------------
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
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."
§ 862.1225 Creatinine test system.
(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.