(27 days)
The Thermo DMA Data-Cal Calibrator is intended for use in the calibration of clinical chemistry assays.
Thermo DMA's Data-Cal is intended for use as a reference material in the single point calibration of clinical chemistry procedures.
Here's an analysis of the provided text regarding the Thermo DMA Data-Cal calibrator, structured to answer your questions.
Description of Acceptance Criteria and Device Performance Study
The primary objective of the studies described in the document is to demonstrate the substantial equivalence of the new Thermo DMA Data-Cal calibrator to its predicate device, the Data Medical Associates (DMA) Data-Cal. This is achieved through comparisons of intended use, format, stability, and most critically, performance in clinical chemistry assays, particularly regarding accuracy and traceability.
The acceptance criteria are implicitly defined by two main aspects:
- Substantial Equivalence: The new calibrator's features and performance should be comparable to the legally marketed predicate device. This is assessed through direct comparison of features and performance characteristics.
- Accuracy and Traceability: The calibrator's assigned values for various analytes should be accurate and traceable to established standards, primarily NIST (National Institute of Standards and Technology) where available. An explicit criterion for performance verification against a secondary calibrator (Verichem) or NIST SRM #909b was set as "to obtain the set point... within +/- 10%".
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Functional Equivalence | Intended use, format, and physical state should match the predicate device. | Met. The new calibrator's intended use ("For the quantitative calibration of clinical chemistry assays"), format ("Pooled human sera with constituents added as required to obtain levels"), and physical state ("lyophilized") are identical to the predicate device. |
| Stability | * Storage Stability: Stable at 2-8°C until expiration date (implied to be equivalent or better than predicate). * Reconstitution Stability: Stable for set number of days after reconstitution (new device proposed 7 days vs. predicate 5 days). | Met. |
| * Accelerated Stability (36 months at 2-8°C equivalent to 21.5 days at 37°C): Performance after accelerated aging should be comparable to non-stressed material and maintain proposed reconstitution stability. * Real-Time Stability: Material stored at 2-8°C should remain stable until its expiration date. | * Accelerated Stability: The calibrator was reconstituted and compared to non-stressed material after being stressed at 37°C for 21.5 days (equivalent to 36 months at 2-8°C). The proposed 7-day reconstitution stability was validated. * Real-Time Stability: The manufacturer documents real-time stability for equivalent calibrators, and samples of the new calibrator will be held for real-time testing. | |
| Value Assignment & Variability | Vial-to-vial variability should be properly evaluated and consistent with predicate devices. | Met. Duplicate tests were run on ten vials, and results were consistent with those obtained from equivalent predicate devices. |
| Accuracy & Traceability | * Analyte values should be traceable to NIST primary standards where available. * Performance verification against secondary calibrator (Verichem) or NIST SRM #909b should be within +/- 10%. | Met (mostly). * Analyte values are traceable to NIST where available (12 specific SRMs listed). Primary standards were produced in-house using NIST SRMs. Where NIST SRMs were unavailable, high purity materials and established clinical chemistry procedures were used, with an established history of known performance. * The +/- 10% criterion was met in all cases during performance transfer, except for instances where the value established fell below one, and specifically for Triglyceride SRM #909b, Level 1 which recovered 14% (outside 10%). Thermo DMA rationalizes that the triglyceride set point is valid because the Verichem material recovered within 6% and the previous lot of calibrator recovered its established set point. * Samples of the predicate calibrator were also included, and their results were consistent with historical performance. |
| Comparative Performance | Results obtained with the new calibrator should not have significant differences compared to the predicate device in clinical chemistry assays. | Met. "No significant differences exist between the results obtained on tests conducted utilizing the Thermo DMA Data-Cal when compared to those obtained when utilizing the predicate device in these studies." |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Value Assignment & Variability: Duplicate tests on ten vials were performed to evaluate vial-to-vial variability.
- Analyte Set Points: Twenty replicates were used to determine the mean analyte set points for the calibrator on the Roche Hitachi 717.
- Performance Transfer: The number of samples for the performance transfer is not explicitly stated as a single number but involved testing the secondary calibrator as an unknown, then using it to calibrate an assay with a primary calibrator (where possible), and including vendor calibrators (Verichem) and NIST SRM #909b. This implies multiple runs for each analyte tested.
- Stability: Not explicitly quantified in terms of "test set" samples, but involved 21.5 days of accelerated aging and comparison to non-stressed material.
- Data Provenance: The data appears to be prospective, generated specifically for this 510(k) submission. The tests were conducted by Thermo DMA in their facilities (e.g., "samples of the calibrator material will be held for real time stability testing at Thermo DMA"). The text does not specify the country of origin beyond "Thermo DMA, Inc. 845 Avenue G East Arlington, Texas 76011".
3. Number of Experts and Qualifications for Ground Truth
- Not Applicable. This submission is for a multi-analyte mixture calibrator, not an imaging or diagnostic device requiring human expert interpretation. Ground truth is established through chemical assays, NIST traceability, and comparison to established predicate device performance.
4. Adjudication Method for the Test Set
- Not Applicable. Since human interpretation or consensus is not involved in establishing the performance of a calibrator, there is no adjudication method in the traditional sense. The "adjudication" is based on instrumental measurements and comparison to defined reference values (NIST, predicate, vendor calibrators).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not Applicable. This is a calibrator for clinical chemistry assays, not a diagnostic device requiring human interpretation, so an MRMC study is not relevant.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Yes, implicitly. The studies described focus entirely on the performance of the calibrator itself, independent of human interpretation or "in-the-loop" assistance. The calibrator's performance is assessed through its interaction with clinical chemistry assay systems (e.g., Roche Hitachi 717) and its ability to provide accurate and traceable reference points for measurements.
7. Type of Ground Truth Used
- Expert Consensus, Pathology, Outcomes Data: None of these.
- Physicochemical and Traceable Standards: The ground truth for the analyte values is established through:
- NIST Primary Standards: Where available, assays were calibrated against NIST primary standards, and Primary Standards were produced in-house utilizing NIST Standard Reference Materials (SRM).
- High Purity Materials and Established Clinical Chemistry Procedures: Where NIST SRMs were not available, standards were prepared using high purity materials according to established analytical procedures with known performance characteristics.
- Comparison to Predicate Device and Vendor Calibrators: The performance was also validated by comparing results to those obtained with the predicate device and a recognized vendor's calibrator (Verichem).
8. Sample Size for the Training Set
- Not Applicable. This is a calibrator, not an AI/ML algorithm that requires a "training set" for model development. The product itself is the "reference material".
9. How the Ground Truth for the Training Set Was Established
- Not Applicable. As there is no training set in the context of this device, this question is not relevant. The closest analogy would be how the assigned values for the calibrator were established, which is detailed in point 7 above.
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Thermo DMA
JUL 2 5 2002
845 Avenue G East Arlington, TX 76011-7709
(817) 607-1700 Fax: (817) 649-2461 www.thermodma.com
510 (k) Summary
This Summary of Safety and Effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
Submitter: Thermo DMA, Inc.
Address: 845 Avenue G East Arlington, Texas 76011
Contact Person: Thomas Dollar, Manager of Regulatory Affairs
The assigned 510 (k) number is
Product Code: JIX, Calibrator, Multi-Analyte Mixture
Device Name: Thermo DMA Data-Cal
Device Class: II
Predicate Device: Data Medical Associates (DMA) Data-Cal
Description and Intended Use: Thermo DMA's Data-Cal is intended for use as a reference material in the single point calibration of clinical chemistry procedures.
Clinical Significance :
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 serum specimens.
Methodology :
Thermo DMA Data-Cal Calibrator is to be used in clinical chemistry assays where it reacts in a manner equivalent to corresponding components present in serum samples.
Substantial Equivalence - Similarities:
| Feature | New calibrator | Current calibrator(Predicate device) |
|---|---|---|
| Intended Use | For the quantitative calibrationof clinical chemistry assays. | For the quantitativecalibration of clinicalchemistry assays. |
| Format | Pooled human sera with constituentsadded as required to obtain levels. | Pooled human sera withconstituents added asrequired to obtain levels. |
| Stability | Stable at 2-8 °C until expirationexpiration date. | Stable at 2-8 °C untilexpiration date. |
| Stable for seven days afterreconstitution. | Stable for five days afterreconstitution. |
Date of Preparation: June 26, 2002
Page 1 of 3
A Thermo Electron business
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| Feature | New calibrator | Current calibrator(Predicate device) |
|---|---|---|
| Levels | single level | single level |
| Physical State | lyophilized | lyophilized |
Differences
There are no significant differences between the two products.
Protocol for accelerated stability: [See Table I - Stability Data]
The product was put at 37°C for 21.5 days. According to the Thermo DMA SOP for Accelerated Stability Testing (SOP #20) this time period is equivalent to 36 months when stored at 2-8° C. After the accelerated storage interval the calibrator was reconstituted and compared to material that had been stored at 2-8° C. Both the stressed and non-stressed materials were then assayed seven days after reconstitution to validate the proposed reconstitution stability claim. In addition to this accelerated evaluation the manufacturer of the calibrator material has documented real time stability data for calibrators of equivalent composition.
Samples of the calibrator material will be held for real time stability testing at Thermo DMA.
Process for value assignment and validation
The values were assigned for this calibrator by assaying the calibrator as unknowns in analyte specific reagents. The assays were calibrated against NIST primary standards where available. In order to insure that vial-to-vial variability was properly evaluated, duplicate tests were run on ten vials. Results obtained in this evaluation were consistent with those obtained in testing conducted on equivalent predicate devices.
Instruments and statistical analysis: [See Table II - Set Points]
For purposes of obtaining data for this protocol Thermo DMA conducted tests using standard procedures applicable to the Roche Hitachi 717 to generate analyte values. Each unknown was assayed in two separate runs using different lot numbers of reagents. These unknowns were run after they had been stored at 2-8° C and at 37°C. The analyte set points for the calibrator were determined by calculating the mean value of twenty replicates.
When subsequent calibrator lots are produced for market distribution, testing will be conducted utilizing multiple analyzers.
Traceability
The analyte values obtained are traceable to NIST material where available. Primary standards were incorporated into testing protocols in order to support accuracy and traceability. These Primary Standards were produced in house utilizing NIST Standard Reference Materials (SRM) in accordance with procedures provided by NIST.
Date of Preparation: June 26, 2002
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Traceability - {continued)
Where NIST SRW's were not available for use in testing, standards were prepared using high purity materials in accordance with established clinical chemistry analytical procedures. These secondary methods have an established history of providing standards with known performance characteristics.
The following SRM materials were utilized in the production of Primary Standards employed;
| Analyte | SRM # |
|---|---|
| a. CO2 | SRM 192b |
| b. Bilirubin | SRM 916a |
| c. BUN | SRM 912a |
| d. Calcium | SRM 915a |
| e. Chloride | SRM 919a |
| f. Cholesterol | SRM 911b |
| g. Creatinine | SRM 914a |
| h. Glucose | SRM 917a |
| i. Iron | SRM 937 |
| j. Magnesium | SRM 929 |
| k. Phosphorus | SRM 186-I-f |
| l. Uric Acid | SRM 913 |
Performance transfer: [See Table III - Verification]
In the case of each analyte the value of the secondary calibrator was determined by assaying it as an unknown sample while calibrating with a primary calibrator. After target values were established, the secondary calibrator was then used to calibrate an assay, which included a primary calibrator when possible.
If no primary standard was available a calibrator from a vendor (Verichem, Inc.) that currently manufacturers and distributes similar products was incorporated into the assay protocol. All verification runs included a serum-based standard from Verichem to confirm that an accurate set point had been determined.
Thermo DMA also included NIST SRM #909b into the testing protocols where appropriate. Our criteria when calibrating against the secondary calibrator was to obtain the set point for the SRM or Verichem within +/- 108. This criterion was met in all cases except for instances in which the value established fell below one, and in the case of Triglyceride SRM #909b, Level 1 which recovered 148. Thermo DMA feels that the triglyceride set point is valid due to the facts that the Verichem material recovers within 6% and the previous lot of calibrator recovers its established set point. Samples of the predicate calibrator were also included in test protocols, the results of which were consistent with historic performance data.
Conclusion: Analysis of the comparative measurements and stability data presented in the 510(k) submission for this calibrator, demonstrates the Thermo DMA Data-Cal Calibrator is safe and effective. No significant differences exist between the results obtained on tests conducted utilizing the Thermo DMA Data-Cal when compared to those obtained when utilizing the predicate device in these studies.
Date of Preparation: June 26, 2002
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
.
Food and Drug Administration 2098 Gaither Road · Rockville MD 20850
Mr. Thomas Dollar Manager of Regulatory Affairs Thermo DMA 845 Avenue G East Arlington, TX 76011-7709
Re: K022108 Trade/Device Name: Thermo DMA Data-Cal Calibrator Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIX Dated: June 27, 2002 Received: June 28, 2002
Dear Mr. Dollar:
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.
JUL 2 5 2002
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 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 Part 801); 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.
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Page 2 -
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and i additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours.
Steven Butman
Steven I. Gutman, M.D., M.B.A. . Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE STATEMENT
<022108 510(K) Number
Device Name: Thermo DMA Data-Cal Calibrator
Indications for Use: The Thermo DMA Data-Cal Calibrator is intended for use in the calibration of clinical chemistry assays.
Sean Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices 510(k) Number
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use (Per 21 CFR 801.109)
OR
Over-the Counter-Use
§ 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.