(28 days)
T-Uptake CalSet is used for calibrating the quantitative Elecsys T-Uptake assay on the Elecsys and cobas e immunoassay analyzers.
Elecsys T-Uptake CalSet: T-Uptake CalSet is a lyophilized buffer/protein/TBG matrix with added L-thyroxine. The Elecsys T-Uptake assay is traceable to a clinically defined human serum panel with a mean TBI (thyroxine-binding index) of 1.
Here's an analysis of the acceptance criteria and the studies performed for the Elecsys T-Uptake CalSet, based on the provided document:
Acceptance Criteria and Reported Device Performance
| Study / Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Value Assignment | Pre-defined acceptance criteria for PreciControl Universal must be met to release Assigned Values for T-Uptake CalSet. | Value assignment testing was conducted and passed pre-defined acceptance criteria. The target values for the two levels are chosen to obtain the best fit with the Reference Standard Curve. For each lot, calibrators are run in duplicate on at least three (3) Elecsys 2010 analyzers and at least three (3) MODULAR ANALYTICS E170 analyzers with all T-Uptake reagent lots available. The assigned value of each calibrator is defined as the median value obtained over at least six (6) runs on at least three (3) analyzers. |
| Stability at 2-8°C, -20°C, in open vial, and freeze/thaw cycles (after reconstitution) | 95-105% signal recovery of the reference material value. | On-test material was reconstituted and stored in closed vials for 85 days at 2-8°C, for 699 days at -15 to -25°C, and for 6 hours at 20-25°C in open vial. Stability for one (1) freeze/thaw cycle was also evaluated. (The document states these conditions were tested, implying they met the criteria, but does not explicitly provide the numerical results or a direct statement of "passed" for each condition, only that the "on-test signal recovery was calculated as percent of the reference value.") |
| Accelerated Stability (35°C for 3 weeks, lyophilized) | 95-105% recovery of the reference material value. | On-test material stored lyophilized at 35°C for 3 weeks was evaluated. (The document states this study was performed with the acceptance criterion, implying passage, but does not explicitly provide numerical results or a direct statement of "passed.") |
| Real-Time Stability (2-8°C, over shelf life) | 95-105% recovery of the reference value (stressed vs. unstressed calibrator). | Real-time stability is being evaluated (planned study), with tests performed in duplicate at specified intervals over the shelf life up to 25 months. The mean value of stressed calibrator is calculated as percent recovery of the unstressed value. (This is a planned/ongoing study, so no final reported performance is available in this document.) |
| Reconstitution Study (15 min vs. 30 min) | 95-105% signal recovery of the reference material value (30 min vs. 15 min reconstitution). | Two sets were reconstituted (15 min and 30 min). Signal recovery after 30 minutes reconstitution was compared to the signal value after 15 minutes. (The document states this study was performed with the acceptance criterion, implying passage, but does not explicitly provide numerical results or a direct statement of "passed.") |
Additional Information on the Studies:
-
Sample size used for the test set and the data provenance:
- Value Assignment: For each Elecsys T-Uptake CalSet lot, calibrators are run in duplicate on at least three (3) Elecsys 2010 analyzers and at least three (3) MODULAR ANALYTICS E170 analyzers. This totals at least 6 analyzers and 12 runs per lot during the value assignment process.
- Stability Studies (Study 1 & 2) and Reconstitution Study: "On-test and reference materials were tested in duplicate." and "One T-Uptake CalSet lot was evaluated in duplicate" on the cobas e 411 analyzer.
- Real-Time Stability (Study 3): CalSets are tested in duplicate at specified intervals.
- Data Provenance: Not explicitly stated, but given the manufacturer (Roche Diagnostics) and the nature of the device (calibrator for immunoassay analyzers), the data is most likely from internal laboratory testing, likely based in Germany (where Roche Diagnostics GmbH is located) or the US. It is prospective testing as part of product development and validation.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This device is a calibrator, not an interpretative diagnostic tool. "Ground truth" in this context refers to the accuracy and stability of the calibrator's assigned values and its performance characteristics. The document mentions that the Elecsys T-Uptake assay is traceable to a "clinically defined human serum panel with a mean TBI of 1.0." This "clinically defined panel" would have been established by experts, but the number and qualifications of those experts are not detailed in this document. The focus of this 510(k) is on the calibrator itself, not the original T-Uptake assay. -
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. This device is a calibrator for an in-vitro diagnostic assay. Adjudication methods like 2+1 or 3+1 are typically used in imaging studies where human readers interpret results and consensus is needed. For this device, performance is measured against predefined analytical values and recovery percentages. -
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. This device is a calibrator for an in-vitro diagnostic assay, not an AI-powered diagnostic system for human reader interpretation. No MRMC study was performed or is relevant for this device. -
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
Not applicable in the usual sense of AI/algorithm standalone performance. The "performance" of this device is its ability to accurately calibrate the Elecsys T-Uptake assay on automated immunoassay analyzers. These analyzers operate without constant human intervention during the measurement process, but the results are interpreted by human operators. The studies conducted (value assignment, stability, reconstitution) are essentially standalone performance evaluations of the calibrator itself within the automated system. -
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ultimate "ground truth" for the T-Uptake assay to which this calibrator relates is a "clinically defined human serum panel with a mean TBI of 1.0." For the calibrator's own performance, the ground truth for comparison is a "reference material" or "unstressed calibrator" with known, freshly reconstituted values, or the established "Reference Standard Curve" for value assignment. -
The sample size for the training set:
Not applicable. This device is a calibrator, not a machine learning algorithm that requires a training set. -
How the ground truth for the training set was established:
Not applicable (no training set for this type of device).
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health and 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 that resembles a stylized caduceus or a representation of the human form.
December 19, 2014
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
ROCHE DIAGNOSTICS KELLI TURNER REGULATORY AFFAIRS PRINCIPAL 9115 HAGUE ROAD, PO BOX 50416 INDIANAPOLIS IN 46250-0416
Re: K143342
Trade/Device Name: Elecsys T-Uptake CalSet Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: November 20, 2014 Received: November 21, 2014
Dear Ms. Kelli Turner:
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 (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.
{1}------------------------------------------------
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/Resourcesfor You/Industry/default.htm. 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
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 -S
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
{2}------------------------------------------------
Indications for Use
510(k) Number (if known)
Device Name Elecsys T-Uptake CalSet
Indications for Use (Describe)
T-Uptake CalSet is used for calibrating the quantitative Elecsys T-Uptake assay on the Elecsys and cobas e immunoassay analyzers.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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."
{3}------------------------------------------------
510(k) Summary, Elecsys T-Uptake CalSet
Introduction According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
The purpose of this premarket notification is to obtain FDA review and clearance for the Elecsys T-Uptake CalSet.
| Submittername, address,contact | Roche Diagnostics9115 Hague Road, P.O. Box 50416Indianapolis, IN 46250-0416Contact Person: Kelli TurnerPhone: 317-521-4515Fax: 317-521-2324Email: kelli.turner@roche.comSecondary Contact: Michael LeutherPhone: 317-521-3930Fax: 317-521-2324Email: michael.leuther@roche.comDate Prepared: December 18, 2014 | |
|---|---|---|
| Device Name | Proprietary name:Common name:Classification:Product Code: | Elecsys T-Uptake CalSetT-Uptake CalSet21 CFR 862.1150, Calibrator, SecondaryJIT |
| EstablishmentRegistration | For the T-Uptake CalSet, the establishment registration number forRoche Diagnostics GmbH in Mannheim, Germany, is 9610126 and forPenzberg, Germany, is 9610529. The establishment registration numberfor Roche Diagnostics United States is 1823260. |
{4}------------------------------------------------
Classification FDA has classified the product as a Class II device.
| Product | Panel | Product | Classification | Regulation | |
|---|---|---|---|---|---|
| Name | Code | Name | Citation | ||
| Elecsys T- | Clinical | JIT | Calibrator, | 21 CFR 862.1150 | |
| Uptake | Chemistry | Secondary | |||
| CalSet | |||||
| DeviceDescription | Elecsys T-Uptake CalSet:● | (thyroxine-binding index) of 1. | T-Uptake CalSet is a lyophilized buffer/protein/TBG matrix withadded L-thyroxine. The Elecsys T-Uptake assay is traceable to aclinically defined human serum panel with a mean TBI | ||
| Intended use | Elecsys T-Uptake CalSet:● | T-Uptake CalSet is used for calibrating the quantitative Elecsys T-Uptake assay on the Elecsys and cobas e immunoassay analyzers. | |||
| Predicatedevice | device Elecsys T-Uptake CalSet (K961488). | The Elecsys T-Uptake CalSet is substantially equivalent to the predicate | |||
| SubstantialEquivalenceComparison | predicate device. | The following tables compare the Elecsys T-Uptake CalSet with the |
{5}------------------------------------------------
| Comparison The table below compares Elecsys T-Uptake CalSet with the predicate | |
|---|---|
| Table | device, Elecsys T-Uptake CalSet (K961488). |
The change in the new product was in the format, going from liquid to lyophilized.
| Characteristic | Elecsys T-Uptake CalSet(Candidate) | Elecsys T-Uptake CalSet(K961488) |
|---|---|---|
| Intended Use | T-Uptake CalSet is used forcalibrating the quantitative ElecsysT-Uptake assay on the Elecsys andcobas e immunoassay analyzers. | Same. |
| Analyte | L-Thyroxine, syntheticThyroxinebinding globuline (TBG), bovine | Same |
| Matrix | Buffer / protein (bovine serumalbumin) / TBG matrix | Same |
| Levels | Two | Same |
| Target Ranges | Cal 1: 0.5 TBI conc.Cal 2: 1.3 TBI conc. | Cal 1: Same.Cal 2: Same. |
| Format | Lyophilized | Liquid, ready-for-use. |
| Stability | Unopened:• Store at 2-8°C until expirationdateOpened:• 2-8°C: 84 days• -20°C: 84 days (freeze onlyonce)Elecsys 2010 and cobas e 411analyzers at 20-25°C:• up to 5 hoursMODULAR ANALYTICS E170,cobas e 601 and cobas e 602:• use only once | Unopened:• Store at 2-8°C until expirationdateOpened:• 2-8°C: 24 hours• 20-25°C: use only once• -20°C: 3 month |
| Table continued | ||
| Characteristic | Elecsys T-Uptake CalSet(Candidate) | Elecsys T-Uptake CalSet(K961488) |
| Handling | Carefully dissolve the contents of onebottle by adding exactly 1.0 mL ofdistilled or deionized water and allowto stand closed for 15 minutes toreconstitute. Mix carefully, avoidingthe foam formation.Transfer the reconstituted calibratorsinto the supplied empty labeled snap-cap bottles.Elecsys 2010 and cobas e 411analyzers: The calibrators should onlybe left on the analyzers duringcalibration at 20-25 °C. After use,close thebottles as soon as possible and storeupright at 2-8 °C.Due to possible evaporation effects,not more than 5 calibration proceduresper bottle set should be performed.If necessary, freeze in aliquots; seesection onMODULAR ANALYTICS E170,cobas e 601 and cobas e 602analyzers.MODULAR ANALYTICS E170,cobas e 601 and cobas e 602analyzers:Unless the entire volume is necessaryfor calibration on the analyzers,transfer aliquots of the reconstitutedcalibrators into empty snap-cap bottles(CalSet Vials). Attach the suppliedlabels to these additional bottles. Storethe aliquots at 2-8 °C or -20 °C forlater use.Perform only one calibrationprocedure per aliquot.. | The calibrators are supplied readyfor use in bottles compatible withthe system.Elecsys 2010 and cobas e 411analyzers: The calibrators shouldonly be left on the analyzersduring calibration at 20-25°C.After use, close the bottles as soonas possible and store at 2-8°C.Due to possible evaporationeffects, not more than 5 calibrationprocedures per bottle set should beperformed.MODULAR ANALYTICS E170,cobas e 601, cobas e 602analyzers: Unless the entirevolume is necessary for calibrationon the analyzers, transfer aliquotsof the ready for use calibrators intoempty snap-cap bottles (CalSetVials). Attach the supplied labelsto these additional bottles. Storethe aliquots at 2-8°C for later use.Perform only one calibrationprocedure per aliquot. |
| Traceability | Standardized using a clinicallydefined human serum panel with amean TBI of 1.0 | Same |
| Traceability | The T-Uptake CalSet has been standardized against a clinically definedhuman serum panel with a mean TBI of 1. | |
| EvaluationsSummary | The Elecsys T-Uptake CalSet was evaluated for value assignment,stability and reconstitution. | |
| CalSet ValueAssignment | Value assignment testing was conducted and passed pre-definedacceptance criteria. The target values for the two levels of the T-UptakeCalSet kit are chosen to obtain the best fit with the Reference StandardCurve. For each Elecsys T-Uptake CalSet lot manufactured, thecalibrators are run in duplicate on at least three (3) Elecsys 2010 analyzersand at least three (3) MODULAR ANALYTICS E170 analyzers with allT-Uptake reagent lots available. The assigned value of each calibrator isdefined as the median value obtained over at least six (6) runs on at leastthree (3) analyzers) of the respective calibrator.Measurement values for PreciControl Universal (Level 1 & 2) are read offfrom the calibration curves generated. The pre-defined acceptance criteriafor PreciControl Universal have to be met to release the Assigned Valuesfor T-Uptake CalSet. | |
| Continued on next page |
Comparison Table
{6}------------------------------------------------
Table continued
{7}------------------------------------------------
{8}------------------------------------------------
Three studies were performed in order to verify the stability claims for Stability Studies the T-Uptake CalSet. Stability studies after reconstitution and an accelerated stability study were completed on the cobas e 411. Additionally, a real-time stability study is planned.
Study 1. Stability at 2-8°C, -20°C, in open vial and freeze/thaw cycles (after reconstitution):
The on-test and reference materials were tested in duplicate. The on-test material was reconstituted and stored in closed vials for 85 days at 2 to 8°C, for 699 days at -15 to -25°C and for 6 hours at 20 to 25°C in open vial. In addition, the stability of the T-Uptake CalSet for one (1) freeze/thaw cycles was evaluated.
The on-test signal recovery was calculated as percent of the reference value. The reference material was a freshly reconstituted set of T-Uptake CalSet.
T-Uptake CalSet was evaluated in duplicate on the cobas e 411. The acceptance criterion was 95 to 105 % signal recovery of the reference material value.
Study 2. Accelerated Stability:
The on-test material was stored lyophilized (as supplied to the user) at 35℃ for 3 weeks. The reference material was a freshly reconstituted set of T-Uptake CalSet (stored at 2 to 8°C). After 3 weeks, the on-test and reference materials were tested in duplicate. The on-test recovery was calculated as a percent of the reference value.
One T-Uptake CalSet lot was evaluated in duplicate on the cobas e 411 analvzer.
The acceptance criterion was 95 to 105 % recovery of the reference material value.
{9}------------------------------------------------
| StabilityStudies,continued | Study 3. Real-Time Stability:In addition, real-time stability is being evaluated as follows:In the real-time stability study, the T-Uptake CalSet test material isstored at 2-8°C. The CalSets are tested in duplicate at specified intervalsover the shelf life of the device up to the planned shelf life plus onemonth (25 months). |
|---|---|
| Real-time stability is calculated based on the recovery of signal ofstressed calibrator (stored at 2-8°C) vs. unstressed calibrator (stored at -20°C). At the specified intervals over the shelf life, the mean value of thestressed calibrator was calculated as percent recovery of the unstressedvalue (each tested in duplicates at the same time point). | |
| The acceptance criterion for T-Uptake Calibrator 1 and 2 is recovery of95-105 % of the reference value. | |
| ReconstitutionStudy | Reconstitution time for the lyophilized T-Uptake CalSet was tested. Twosets of T-Uptake CalSet were reconstituted, one for 15 minutes and theother for 30 minutes. Signal recovery after 30 minutes reconstitution wascompared to the signal value after 15 minutes. |
| T-Uptake CalSet was evaluated in duplicate on the cobas e 411 analyzeras a reference. | |
| The acceptance criterion was 95 to 105 % signal recovery of the referencematerial value. | |
| Conclusion | We trust that the data and information provided in this PremarketNotification (510(k)) will support a determination of substantialequivalence for the Elecsys T-Uptake CalSet. The data supports a safeeffective device which performs as well as or better than the predicatedevice. |
§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.