(147 days)
Not Found
No
The summary describes a laboratory kit for quantifying a drug using LC/MS/MS, a standard analytical technique. There is no mention of AI, ML, or any computational analysis beyond standard data processing for quantification.
No
This device is an in vitro diagnostic (IVD) device used for monitoring drug levels, which aids in managing patient dosing, but it does not directly treat or prevent a disease or condition.
Yes
The device is indicated for the quantification of Tacrolimus in blood samples for monitoring drug levels to direct patient dosing, which is a diagnostic purpose. The device description also states it is an "in vitro medical device intended to facilitate quantitative determination of Tacrolimus in human whole blood as an aid in the management of kidney and liver transplant patients."
No
The device description explicitly states that the kit includes physical components such as calibrators, quality control materials, internal standards, neat solutions, and a C18 cartridge column, which are hardware components.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states the device is "indicated for the quantification of the immunosuppressive drug Tacrolimus... in liver and kidney transplant patient whole blood samples for the purposes of monitoring drug levels to direct subsequent patient dosing." This describes a test performed on a biological sample (whole blood) outside of the body to provide information for medical purposes (monitoring drug levels for dosing).
- Device Description: The "Device Description" further clarifies that it is an "in vitro medical device intended to facilitate quantitative determination of Tacrolimus in human whole blood as an aid in the management of kidney and liver transplant patients." The term "in vitro" directly means "in glass" or "outside the body," which is a key characteristic of IVDs.
- Components: The description of the kit components (calibrators, quality control materials, internal standards, neat solutions, and a column) are typical components of an IVD kit used for laboratory testing.
- Performance Studies: The "Summary of Performance Studies" describes analytical and comparison studies conducted to validate the performance of the device for its intended use, which is a requirement for IVDs.
- Predicate Devices: The mention of "Predicate Device(s)" with K numbers (K063868) indicates that this device is being compared to previously cleared IVDs, further confirming its classification.
All of these points strongly support the conclusion that the Waters MassTrak Immunosuppressants Kit is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Waters MassTrak Immunosuppressants Kit is indicated for the quantification of the immunosuppressive drug Tacrolimus (FK506; Prograf) in liver and kidney transplant patient whole blood samples for the purposes of monitoring drug levels to direct subsequent patient dosing.
Product codes
MLM, JIT, JJX
Device Description
The MassTrak Immunosuppressants Kit for Tacrolimus is an in vitro medical device intended to facilitate quantitative determination of Tacrolimus in human whole blood as an aid in the management of kidney and liver transplant patients receiving Tacrolimus drug therapy. Tacrolimus (FK506) is an immunosuppressive agent approved by FDA that has been successfully implemented following the transplantation of kidney and liver organs. Monitoring and maintenance of appropriate blood levels of Tacrolimus is important to prevent rejection, infection, and other adverse events. Analytical methodology using a high-performance liquid chromatography (HPLC) apparatus equipped with a tandem mass spectrometer detector (LC/MS/MS) is considered to be a candidate reference method for Tacrolimus quantification. Sample preparation is based on simple protein precipitation and centrifugation to isolate the supernatant that is suitable for analysis by LC/MS/MS. The components of the kit are intended for use with an LC/MS/MS system. The kit materials - calibrators, quality control materials, internal standards, and neat solutions, as well as a MassTrakTM 2.1 x 10 mm C18 cartridge column - have been optimized for use with the Waters Quattro micro and Alliance 2795 System, but can be used with any LC/MS/MS configuration optimized for quantification. System calibration is performed using the kit calibrators, and analysis is completed with the aid of the internal standard, ascomycin. The neat solution is used only for tuning the mass spectrometer. The HPLC cartridge columns was selected to isolate Tacrolimus from compounds extracted from the sample that may lead to ion suppression.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
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
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Summary of Performance Studies
- Analytical Performance:
a. Precision/Reproducibility: Precision studies were conducted by assaying three levels of spiked whole blood pools according to CLSI EP5-A2. The pools were prepared from EDTA drug free whole blood with Tacrolimus spiked at three analytical levels: Low, Medium and High. Specimens at each level were analyzed in duplicate twice per day for 20 days. For within-run precision and total precision, a coefficient of variation (%CV) = 0.05) or caused a change of 15ng/mL were analyzed before and after 1:1 dilution with drug-free whole blood and 1:1 dilution with MassTrak Immunosuppressants Kit Calibrator 1. The results were considered acceptable if, for each sample, the Tacrolimus concentration measured for the undiluted sample and the Tacrolimus concentration calculated from the sample diluted 1:1 with drugfree whole blood or MassTrak Immunosuppressants Kit Calibrator 1 varied by 10% is considered to have a significant effect and must be investigated further to determine the maximum concentration at which no interference is observed.
g. Accuracy: The accuracy of the measurements performed using the MassTrak Immunosuppressants Kits was established by measuring the Tacrolimus concentrations in a series of 44 samples provided by the Tacrolimus International Proficiency Testing Scheme (www.bioanalytics.co.uk). The results for all samples were considered acceptable by the Scheme (±3 SD of method mean). - Comparison Studies:
a. Method Comparison: Method comparison studies were conducted according to CLSI EP9-A2 to compare the results obtained with the MassTrak Immunosuppressants Kit (the "Test Method") with those obtained using the test laboratory's current methodology (the "Comparative Method"). According to the FDA Special Controls Document, a minimum of 50 samples for each transplant type were compared at each site. Duplicate analyses of each patient sample were performed in each of two Test Method assays and two Comparative Method assays, with all four assays performed on the same day. A maximum of 10 patient samples were compared in one day. The predicted bias at the lower (5 ng/mL) and upper (15 ng/mL) limits of the therapeutic range for Tacrolimus (Lake Louise Consensus Conference on Tacrolimus monitoring, Oellerich et al, 1998) are calculated using Deming Regression analysis as described in EP9-A2 and the results of the Test Method for each tissue type are considered acceptable if the bias at both concentrations is
§ 862.1678 Tacrolimus test system.
(a)
Identification. A tacrolimus test system is a device intended to quantitatively determine tacrolimus concentrations as an aid in the management of transplant patients receiving therapy with this drug. This generic type of device includes immunoassays and chromatographic assays for tacrolimus.(b)
Classification. Class II (special controls). The special control is “Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA.” See § 862.1(d) for the availability of this guidance document.
0
510(k) SUMMARY
Date of Summary: December 28, 2006
Product Name
Waters MassTrakTM Immunosuppressants Kit
Sponsor
Waters Corporation 34 Maple Street Milford, MA 01757
Manufacturer
Chromsystems Instruments & Chemicals GmbH Heimburgstr. 3 D-81243 München, Germany
Correspondent
Fran White, President MDC Associates, LLC 163 Cabot Street Beverly, MA 01915
| telephone: | (978) 927-3808 |
|---|---|
| facsimile: | (978) 927-1308 |
| email: | fran@mdcassoc.com |
Substantially Equivalent Devices
The MassTrak Immunosuppressants Kit is substantially equivalent to the Dade Behring Emit® 2000 Tacrolimus Assay and Calibrators and the Microgenics CEDIA® Tacrolimus Assay and Calibrators in its intended use and for the quantitative determination of Tacrolimus concentration in human whole blood as an aid in the management of kidney and liver transplant patients receiving therapy with Tacrolimus.
| ITEM | DEVICE | PREDICATE I | PREDICATE II |
|---|---|---|---|
| Intended Use | The Waters MassTrakTM | ||
| Immunosuppressants Kit | |||
| is indicated for the | |||
| quantification of the | |||
| immunosuppressive drug | |||
| Tacrolimus (FK506; | |||
| Prograf) in liver and | |||
| kidney transplant patient | |||
| whole blood samples for | |||
| the purposes of | |||
| monitoring drug levels to | |||
| direct subsequent patient | |||
| dosing. | Intended for in vitro | ||
| quantitative analysis of | |||
| Tacrolimus and | |||
| metabolite in human | |||
| whole blood as an aid in | |||
| the management of | |||
| Tacrolimus therapy in | |||
| liver and kidney | |||
| transplant patients. |
The Emit® 2000
Tacrolimus Calibrators are
intended for use as a
reference in measuring
Tacrolimus in human
whole blood using the | Intended for the quantitative
determination of Tacrolimus
in human whole blood using
automated clinical chemistry
analyzers as an aid in the
management of kidney and
liver transplant recipients
receiving Tacrolimus
therapy.
CEDIA® Tacrolimus
Calibrators are intended for
calibration of the CEDIA®
Tacrolimus
Assay in whole blood. |
MAY 25 2007
1
| ITEM | DEVICE | PREDICATE I | PREDICATE II |
|---|---|---|---|
| Waters MassTrak™ | |||
| Immunosuppressants Kit | Emit® 2000 Tacrolimus | ||
| Assay | CEDIA® Tacrolimus Assay | ||
| Emit® 2000 Tacrolimus | |||
| Calibrators | |||
| Emit® 2000 Tacrolimus | |||
| Assay. | CEDIA® Tacrolimus | ||
| Calibrators | |||
| Analyte | Tacrolimus | Tacrolimus | Tacrolimus |
| Matrix | Whole blood | Whole blood | Whole blood |
| Assay range | 3-30 ng/mL | 2-30 ng/mL | 2-30 ng/mL |
| Analytical | |||
| specificity | Liquid chromatography / | ||
| tandem mass | |||
| spectrometry | |||
| (LC/MS/MS) | EMIT (Enzyme Multiplied | ||
| Immunoassay | |||
| Technology) | Clinical Chemistry Analyzer | ||
| Calibrator | Six (6) levels | ||
| (0 ng/mL 3 ng/mL, 6 | |||
| ng/mL, 12 ng/mL, 20 | |||
| ng/mL, and 30 ng/mL of | |||
| Tacrolimus) | Six (6) levels | ||
| (0 ng/mL 2.5 ng/mL, 5 | |||
| ng/mL, 10 ng/mL, 20 | |||
| ng/mL, and 30 ng/mL of | |||
| Tacrolimus) | Two (2) levels | ||
| (0 and 30ng/mL) | |||
| Storage | Kit is stored at -20°C | ||
| Reconstituted calibrators | |||
| and QCs are stored at 2°C | |||
| to 8°C | Reagents are stored at 2°C | ||
| to 8°C | Reagents are stored at 2°C to | ||
| 8°C | |||
| Calibrators are stored at | |||
| -20°C | |||
| Stability | Kit stable for up to 2 years | ||
| from manufacture date | |||
| when stored as indicated | |||
| above | Reagents stable for up to | ||
| 18 months from | |||
| manufacture date when | |||
| stored as indicated above | Reagents and Calibrators | ||
| stable for up to 24 months | |||
| from manufacture date | |||
| when stored as indicated | |||
| above |
Product Description
The MassTrak Immunosuppressants Kit for Tacrolimus is an in vitro medical device intended to facilitate quantitative determination of Tacrolimus in human whole blood as an aid in the management of kidney and liver transplant patients receiving Tacrolimus drug therapy.
Tacrolimus (FK506) is an immunosuppressive agent approved by FDA that has been successfully implemented following the transplantation of kidney and liver organs. Monitoring and maintenance of appropriate blood levels of Tacrolimus is important to prevent rejection, infection, and other adverse events. Analytical methodology using a high-performance liquid chromatography (HPLC) apparatus equipped with a tandem mass spectrometer detector (LC/MS/MS) is considered to be a candidate reference method for Tacrolimus quantification. Sample preparation is based on simple protein precipitation and centrifugation to isolate the supernatant that is suitable for analysis by LC/MS/MS.
The components of the kit are intended for use with an LC/MS/MS system. The kit
2
materials - calibrators, quality control materials, internal standards, and neat solutions, as well as a MassTrakTM 2.1 x 10 mm C18 cartridge column - have been optimized for use with the Waters Quattro micro and Alliance 2795 System, but can be used with any LC/MS/MS configuration optimized for quantification. System calibration is performed using the kit calibrators, and analysis is completed with the aid of the internal standard, ascomycin. The neat solution is used only for tuning the mass spectrometer. The HPLC cartridge columns was selected to isolate Tacrolimus from compounds extracted from the sample that may lead to ion suppression.
Intended Use
The Waters MassTrak Immunosuppressants Kit is indicated for the quantification of the immunosuppressive drug Tacrolimus (FK506; Prograf) in liver and kidney transplant patient whole blood samples for the purposes of monitoring drug levels to direct subsequent patient dosing.
Summary of Technology
Sample preparation is based on simple protein precipitation. Whole-blood samples are treated with an organic solvent to precipitate the protein and extract the compound of interest into the organic phase. The supernatant from a protein-precipitated whole-blood sample is injected into an on-line, solid phase, extraction device to perform a preliminary clean-up of the prepared sample. The internal standard and analyte of interest are then eluted into the ionization source of the tandem mass spectrometer.
The first stage of mass spectrometry selects precursor ions from the ion source according to their mass-to-charge ratios (m/z). Ions whose m/z ratios correspond to that of the analyte of interest are passed to a collision cell where they collide with a neutral gas, generating structurally specific product ions. The second stage of mass spectrometry passes ions corresponding to one of these product ions (usually the most abundant) to the detector. Therefore, interferences with the signal generated by the analyte of interest will be seen only if the interfering chemical entity generates precursor and product ions of the same m/z values (that is, structural isomers),
The assay method requires the user to tune the instrument in the presence of ammonium acetate. Ammonium adducts are created which are then measured by the mass spectrometer. The most prominent product ion (m/z 768) of the ammonium adduct of Tacrolimus (m/z 821) is detected using tandem mass spectrometry. The measured response of Tacrolimus is compared to the measured response of the internal standard.
The quantification of Tacrolimus in whole blood extracts is made against a linear standard curve prepared using reconstituted freeze-dried whole blood matrix calibrators (6 levels, with targets varying by lot number). The analysis is controlled using three levels of reconstituted freeze-dried whole blood matrix quality control materials (with targets varying by lot number).
Performance Data
All performance data for the MassTrak Immunosuppressants Kit were gathered at the clinical sites using Alliance HT 2795 High Performance Liquid Chromatography Systems
3
coupled to Quattro micro triple quadrupole mass spectrometers. Data and results are presented in Section 20: Design Testing Summary Report of the 510(k) submission.
-
- Analytical Performance:
- a. Precision/Reproducibility
Precision studies were conducted by assaying three levels of spiked whole blood pools according to CLSI EP5-A2. The pools were prepared from EDTA drug free whole blood with Tacrolimus spiked at three analytical levels: Low, Medium and High. Specimens at each level were analyzed in duplicate twice per day for 20 days. For within-run precision and total precision, a coefficient of variation (%CV) ≤ 10% is deemed acceptable.
-
b. Linearity/assay reportable range
Linearity was assessed according to CLSI EP6-A using nine test samples. The test samples were prepared by mixing patient specimens with low and high Tacrolimus concentrations in defined proportions such that the final Tacrolimus concentrations were known relative to each other. Replicate determinations of each test sample were made. Second order and third order polynomial curves are fitted to the data and the assay is deemed to be linear if the coefficients for the second order and third order terms are not significantly different from zero at the 95% confidence level. -
c. Patient Sample Stability
Patient samples were analyzed in replicate before and after storage under defined conditions to determine the effect of those conditions on the Tacrolimus concentration measured by the device. A freeze-thaw study (three cycles) was also conducted. Conditions that did not cause a statistically significant change from the initial Tacrolimus concentration (ttest, p ≥ 0.05) or caused a change of ≤ 10% from the initial Tacrolimus concentration were acceptable. -
d. Sample Dilution
A minimum of ten patient samples with Tacrolimus concentrations > 15ng/mL were analyzed before and after 1:1 dilution with drug-free whole blood and 1:1 dilution with MassTrak Immunosuppressants Kit Calibrator 1. The results were considered acceptable if, for each sample, the Tacrolimus concentration measured for the undiluted sample and the Tacrolimus concentration calculated from the sample diluted 1:1 with drugfree whole blood or MassTrak Immunosuppressants Kit Calibrator 1 varied by ≤ 10% of the initial concentration. -
Spike & Recovery e.
The recovery performance of the device was assessed using patient samples supplemented with 5, 10 or 20 ng/mL Tacrolimus and using drug-free whole blood spiked with Tacrolimus from 0.5 - 30 ng/mL to ensure that the analytical range of the assay was covered. Triplicate determinations of each sample were made and recovery is considered acceptable if the overall
4
mean recovery for each concentration is in the range 90% - 110%.
-
f. Interference Studies
Potential interferences were evaluated according to CLSI EP7-A and with reference to the list of potential interfering substances in the FDA Class II Special Controls Document and in the FDA Guidance for Industry Bioanalytical Method Validation Document. Known amounts of exogenous or endogenous materials were spiked into separate aliquots of a base pool of drug-free whole blood that had been supplemented with Tacrolimus at a concentration of approximately 20 ng/mL. To test the effect of anticoagulants at up to 5x the normal concentration and to test the effect of hematocrit 15% to 60%, drug-free whole blood was first adjusted to simulate the appropriate condition before spiking with Tacrolimus to a concentration of approximately 20 ng/mL. In all cases, sufficient replicate determinations were made to ensure 95% confidence and 95% power. Any interference that causes a change in measured Tacrolimus concentration of > 10% is considered to have a significant effect and must be investigated further to determine the maximum concentration at which no interference is observed. -
g. Accuracy
The accuracy of the measurements performed using the MassTrak Immunosuppressants Kits was established by measuring the Tacrolimus concentrations in a series of 44 samples provided by the Tacrolimus International Proficiency Testing Scheme (www.bioanalytics.co.uk). The results for all samples were considered acceptable by the Scheme (±3 SD of method mean).
2. Comparison Studies
- Method Comparison a.
Method comparison studies were conducted according to CLSI EP9-A2 to compare the results obtained with the MassTrak Immunosuppressants Kit (the "Test Method") with those obtained using the test laboratory's current methodology (the "Comparative Method"). According to the FDA Special Controls Document, a minimum of 50 samples for each transplant type were compared at each site. Duplicate analyses of each patient sample were performed in each of two Test Method assays and two Comparative Method assays, with all four assays performed on the same day. A maximum of 10 patient samples were compared in one day. The predicted bias at the lower (5 ng/mL) and upper (15 ng/mL) limits of the therapeutic range for Tacrolimus (Lake Louise Consensus Conference on Tacrolimus monitoring, Oellerich et al, 1998) are calculated using Deming Regression analysis as described in EP9-A2 and the results of the Test Method for each tissue type are considered acceptable if the bias at both concentrations is ≤ 10% .
In addition, the Tacrolimus concentrations for a series of International Proficiency Testing Samples (http://www.bioanalytics.co.uk/html/
5
tacrolimus scheme.html) were determined using the MassTrakTM Immunosuppressants Kit and the results compared to those reported to the Scheme for the same samples analyzed using the EMIT 2000 Tacrolimus device.
Statement of Safety and Efficacy
The information provided in this pre-market notification demonstrates that the MassTrak Immunosuppressants Kit is substantially equivalent to the currently-marketed CEDIA® Tacrolimus Assay and Emit® 2000 Tacrolimus Assay.
Waters Corporation has presented laboratory testing in this pre-market notification. Data and results were collected and prepared in accordance with the established guideline, "Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA" September 16, 2002.
The information presented provides assurance that the MassTrak Immunosuppressants Kit will meet the requirements that are considered acceptable for its intended use.
6
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three lines forming its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAY 2 5 2007
Waters Corporation c/o Ms. Fran White MDC Associates, LLC 163 Cabot Street Beverly, MA 01915
Re: K063868
Trade/Device Name: MassTrak™ Immunosuppressants Kit Regulation Number: 21 CFR 862.1678 Regulation Name: Tacrolimus test system Regulatory Class: Class II Product Code: MLM, JIT, JJX Dated: May 18, 2007 Received: May 21, 2007
·Dear Ms. White:
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).
7
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 Iogally 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 (240) 276-0490. Also, please cotte 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 tolloffree mumber (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Jean M. Cooper, M.S., D.V.M.
Séan M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
8
Indications for Use
510(k) Number (if known):
Waters MassTrak™ Immunosuppressants Kit Device Name:
Indications For Use:
The Waters MassTrak Immunosuppressants Kit is indicated for the quantification of the immunosuppressive drug Tacrolimus (FK506; Prograf) in liver and kidney transplant patient whole blood samples as an aid in the management of tacrolimus therapy.
Prescription Use XXX (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off
Division Diagnostic Device
Office of In Vitro Diagnostic Device
Office in and Safety Office of and Safety
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