Thermo Scientific Cyto-Cal™ Count Tubes are used with the immunophenotyping reagents BD TriTEST™, flow cytometers BD FACS Calibur or BD FACS Canto, and software BD CellQuest or DIVA. Thermo Scientific Cyto-Cal™ Count Tubes can be used with the BD FACS™ Loader. This in vitro diagnostic device is intended for clinical use only.

Device Description

Thermo Scientific Cyto-Cal™ Count Tubes contain uniform 5.4 µm microspheres encapsulated with three dyes. The single tube contains fluorescent beads that have equivalent emissions to multiple channels for FITC. PE. Per-CP. PE-Cy5, APC. Each tube contains known number of fluorescent particles as indicated on the product label.

AI/ML Overview

The provided text describes the 510(k) summary for the Thermo Scientific Cyto-Cal™ Count Tubes. Here's a breakdown of the acceptance criteria and the study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance

The document doesn't explicitly list "acceptance criteria" in a separate table with pass/fail remarks. However, it presents the results of several performance studies that imply the acceptance criteria were met based on the conclusion of substantial equivalence to the predicate device.

Study Type	Implied Acceptance Criteria (Based on Predicate Equivalence)	Reported Device Performance (Thermo Scientific Cyto-Cal™ Count Tubes)
Precision	Comparable CVs to predicate device for low, medium, and high cell levels.	Intra-assay precision:- CD3+ cells: CVs ranged from 4.9% (3602 cells/µL) to 6.2% (549 cells/µL).- CD4+ cells: CVs ranged from 4.7% (1996 cells/µL) to 6.9% (369 cells/µL).
Dilution Recovery	Recovery within +/- X% of expected value.	Recovery was within +/- 10% of expected value for levels tested:- 0 to 1693 cells/µL for CD3+CD4+ cells.- 0 to 3923 cells/µL for CD3+ cells.
Method Comparison	Strong correlation (R value > 0.99) with the predicate device.	Correlation Coefficient (R value) to predicate BD Trucount Tubes:- CD3+: > 0.99 (range 1 cell/µL to 2463 cells/µL).- CD4+: > 0.99 (range 0 cells/µL to 1947 cells/µL).External Evaluation: Correlation coefficients (r-value) met acceptance criteria for CD3+, CD4+, CD8+, CD16+CD56+, CD19+, and CD4/CD8 ratio.
Carryover Study	Carry-over less than X%.	Carry-over from high cell count sample to low cell count sample is less than 5%.
Sample Stability	Cells count within +/- X% of first test for specified times and temperatures.	Cells count are within +/- 10% of first test for up to 72 hours at 2 to 8 °C for blood samples, and for up to 12 hours at 2 to 8 °C for antibody-labeled and lysed blood samples.
Reagent Shelf-Life Stabilities	Stable for X months at specified temperature.	Real-time stability studies demonstrate the reagent is stable for at least 16 months at room temperature. Stability studies will continue for 24 months.

2. Sample size used for the test set and the data provenance

Precision:
- Sample Size: Three samples (representing low, medium, and high cell levels of CD3+ and CD4+) were used. Each sample was run 21 times.
- Data Provenance: Not specified, but generally, these are laboratory-controlled samples for repeatability.
Dilution Recovery:
- Sample Size: Not explicitly stated how many individual samples were tested, but it covered levels from 0 to 1693 cells/µL for CD3+CD4+ cells and 0 to 3923 cells/µL for CD3+ cells.
- Data Provenance: Not specified.
Method Comparison:
- Sample Size: 70 samples.
- Data Provenance: Not specified, but the context suggests these are human blood samples. The study was likely prospective to directly compare the new device with the predicate.
Carryover Study:
- Sample Size: Not specified, but involves high and low cell count samples.
- Data Provenance: Not specified.
Sample Stability:
- Sample Size: Not specified.
- Data Provenance: Not specified, but blood samples were used.
Reagent Shelf-Life Stabilities:
- Sample Size: Not specified.
- Data Provenance: Not specified, but real-time stability studies imply laboratory-controlled experiments.
External Evaluation:
- Sample Size: Not explicitly stated for this part, but it references "a wide panel" and "All of the method comparison results" which suggests it replicates or expands on the internal method comparison potentially with different samples or a larger set for the specific cell types mentioned.
- Data Provenance: "External site studies" implies data from a different laboratory or clinical setting than the manufacturer's. This would likely be a prospective comparison.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This device is an automated cell counter, not an interpretative AI/diagnostic imaging device. Therefore, the concept of "experts" establishing a "ground truth" for interpretation, as would be the case for radiologists, does not directly apply here.

The "ground truth" for comparison for the Cyto-Cal™ Count Tubes is established by the predicate device, BD Trucount Tubes, which is also an automated cell counting system. The performance of the predicate device serves as the reference, and the new device is evaluated against its readings rather than human expert interpretations.

4. Adjudication method for the test set

Not applicable in the traditional sense for an automated cell counter. The comparison is directly between the new device and the predicate device. There is no human interpretation or adjudication involved to establish a "ground truth" for each sample in the way it would be for a diagnostic image.

5. 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 an automated in vitro diagnostic used for absolute cell counts. It does not involve human readers for interpretation, nor does it provide AI assistance to human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the studies described (Precision, Dilution Recovery, Method Comparison, Carryover, Stability) are all standalone performance evaluations of the Thermo Scientific Cyto-Cal™ Count Tubes without human intervention in the counting process itself. The device is designed to operate as an automated system.

7. The type of ground truth used

The ground truth used for comparison is the results obtained from the predicate device, BD Trucount Tubes. This is a comparative method study, where the new device's performance is gauged by its agreement with an already legally marketed and accepted device.

8. The sample size for the training set

The document does not mention "training set" or "training data" as it would for a machine learning model. This is a traditional in vitro diagnostic device, not an AI/ML algorithm that requires a separate training phase. The "development" of the device would involve internal testing and optimization that might use many samples, but it's not structured as a "training set" in the AI sense.

9. How the ground truth for the training set was established

Not applicable, as there is no mention of a "training set" in the context of an AI/ML algorithm.

Summary

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SEP 1 8 2009

510K SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of Safe Medical Devices Act of 1990 and 21 CFR 807.92

The assigned 510(k) number is: K090810

COMPANY/CONTACT PERSON

Lisa Charter

Manager of Regulatory Affairs Microgenics Corporation Thermo Fisher Scientific, Clinical Diagnostics Division 46360 Fremont Blvd. Fremont, CA 94538 (510) 979-5142 Office (510) 979-5422 Fax Lisa. Charter@thermofisher.com

DATE PREPARED

August 30, 2009

DEVICE NAME

Trade Name:	Thermo Scientific Cyto-Cal™ Count Tubes
Common Name:	Cyto-Cal™ Count Tubes
Device Classification:	Automated Differential Cell Counter
Regulation number:	21 CFR 864.5220
Product Code:	GKZ

INTENDED USE

Thermo Scientific Cyto-Cal™ Count Tubes are used for determining absolute counts of leucocytes in blood.

Thermo Scientific Cyto-Cal™ Count Tubes are used with the immunophenotyping reagents BD TriTEST™, flow cytometers BD FACS Calibur or BD FACS Canto, and software BD CellQuest or DIVA. Thermo Scientific Cyto-Cal[" Count Tubes can be used with the BD FACS™ Loader. This in vitro diagnostic device is intended for clinical use only.

SUBSTANȚIALLY EQUIVILANT PREDICATE DEVICE

Thermo Scientific Cyto-Cal™ Count Tubes are substantially equivalent to the previously cleared BD Trucount Tubes (K965053)

DESCRIPTION OF DEVICE

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PRINCIPLES OF THE PROCEDURE

Procedures described herein apply to immunophenotyping of lymphocytes. In the procedure, the cell typing monoclonal antibody reagent and whole blood is added directly to the Cyto-Cal™ Count Tube. The dried pellet in the tube dissolves, releasing a known number of fluorescent beads. During analysis, the absolute number (cells/μL) of positive cells in the sample can be determined by comparing cellular events to bead events. If you are manually performing data analysis, simply divide the number of positive cellular events by the number of bead events, and then multiply by the Cyto-Cal Count bead concentration. The cell typing or immunophenotyping of lymphocytes is effectively used in monitoring immune response or in determining a particular cell count.

Comparison	Predicate Device - BD Trucount Tubes	Thermo Scientific Cyto-Cal™ Count Tubes
Intended Use	BD Trucount Tubes are used for determining absolute counts of leucocytes in blood. BD Trucount Tubes are designed for use with in vitro diagnostic products such as BD TriTEST™ reagents, and a suitably equipped flow cytometer. BD Trucount Tubes can be used with the BD FACS™ Loader.	Thermo Scientific Cyto-Cal™ Count Tubes are used for determining absolute counts of leucocytes in blood.Thermo Scientific Cyto-Cal™ Count Tubes are used with the immunophenotyping reagents BD TriTEST™, flow cytometers BD FACS Calibur or BD FACS Canto, and software BD CellQuest or DIVA. Thermo Scientific Cyto-Cal™ Count Tubes can be used with the BD FACS™ Loader.This in vitro diagnostic device is intended for clinical use only.
Test Principle	Add the cell typing monoclonal antibody reagent and whole blood directly to the BD Trucount Tubes. The lyophilized pellet in the tube dissolves, releasing a known number of fluorescent beads. During analysis, the absolute number (cells/µL) of positive cells in the sample can be determined by comparing cellular events to bead events. If the appropriate software, such as BD MultiSET™, is used, absolute counts will be determined by the software. If you are manually performing data analysis using software such as BD CellQuest™, simply divide the number of positive cellular events by the number of bead events, then multiply by the BD Trucount bead concentration.	Add the cell typing monoclonal antibody reagent and whole blood directly to the Thermo Scientific Cyto-Cal™ Count Tubes. The dried pellet in the tube dissolves, releasing a known number of fluorescent beads. During analysis, the absolute number (cells/µL) of positive cells in the sample can be determined by comparing cellular events to bead events. If the appropriate software, such as BD MultiSET™, is used, absolute counts will be determined by the software. If you are manually performing data analysis using software such as BD CellQuest™ divide the number of positive cellular events by the number of bead events, then multiply by the Thermo Scientific Cyto-Cal™ Count bead concentration.

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

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Matrix	Freeze-dried pellet of fluorescentbeads in a single-use tube.	Dried pellet of fluorescent beads ina single-use tube.
Reagents	Each pouch contains 25 BDTrucount Tubes, sufficient for 25tests.	Each package contains 25 ThermoScientific Cyto-Cal™ Count Tubes,sufficient for 25 tests.
Instrument	Flow cytometer	Flow cytometer
Storage Condition	2 to 25 °C	20 to 25 °C
ParticleConcentration	~50,000/tube	~50,000/tube
Lysing reagent	FACSLyse	FACSLyse

SUMMARY OF CLINICAL TESTING

Precision

Three samples representing low, medium and high cell levels of CD3+ and CD4+ were used for these studies. Each sample was run 21 times to collect intra-assay precision data. The range of CVs for CD3+ cells, observed for all samples, was 4.9% (count of 3602 cells/μL) to 6.2% (count of 549 cells/μL). The range of CVs for CD4+ cells, observed for all samples, was 4.7% (count of 1996 cells/uL) to 6.9% (count of 369 cells/uL).

Dilution Recovery

Recovery was within +/_ 10% of expected value for levels tested from 0 to 1693 cells/pl. for CD3+CD4+ cells and 0 to 3923 cells/uL for CD3+ cells.

Method Comparison

We have selected a 70 samples for this study representing a wide range of results. For CD3+ the range is 1 cell / uL to 2463 cells / µL. For CD4+ the range is 0 cells / µL to 1947 cells / µL. There is strong correlation between Thermo Scientific Cyto-Cal™ Count Tubes and the predicate BD Trucount Tubes in all of these ranges. The correlation coefficient (R value) for both CD3+ and CD4+ to reference method is > than 0.99.

Carryover Study

Carry-over from a high cell count sample to a low cell count sample is less than 5%. :

Sample Stability

Cells count are within +/-10% of first test for up to 72 hours at 2 to 8 °C for blood samples, and for up to 12 hours at 2 to 8 ℃ for antibody labeled and lysed blood samples.

Reagent Shelf-Life Stabilities

Real time stability studies demonstrate the reagent is stable for at least 16 months at room temperature. Stability studies will continue for 24 months.

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External Evaluation

The external site studies included a wide panel for fluorescent labeled monoclonal antibody (CD3, CD4, CD8, CD16, CD19, and CD56). The commonly used cell types including CD3+, CD4+, CD8+, CD16+CD56+, CD19+, and CD4/CD8 ratio are tabulated and compared to the reference BD Trucount method and Thermo Scientific Cyto-Cal™ Count Tubes method All of the method comparison results show a strong correlation between Thermo Scientific Cyto-Cal™ Count Tubes and the predicate BD Trucount Tubes in all of these cell types. The correlation coefficients (rvalue) meet the acceptance criteria.

CONCLUSION

As summarized, the Thermo Scientific Cyto-Cal™ Count Tubes are substantially equivalent to the BD Trucount Tubes. Substantial equivalence has been demonstrated through performance testing to verify that the device functions as intended and that design specifications have been satisfied.

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Image /page/4/Picture/1 description: The image shows the seal for the Department of Health & Human Services - USA. The seal is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract image of an eagle.

SEP 1 8 2009

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G609 Silver Spring, MD 20993-0002

Microgenics Corporation Thermo Fisher Scientific, Clinical Division c/o Lisa Charter Manager, Regulatory Affairs 46360 Fremont Boulevard Fremont, CA 94538

Re: K090810

Trade/Device Name: Thermo Scientific Cyto-Cal™ Count Tubes Regulation Number: 21 CFR 864.5220 Regulation Name: Differential Cell Counter Regulatory Class: Class II Product Code: GKZ Dated: September 2, 2009 Received: September 4, 2009

Dear Ms. Charter:

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. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into class II (Special Controls), 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter

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Page 2 - Ms. Lisa Charter

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 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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Marie M. Chan

Maria M. Chan, PhD Director Division of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number (if known): K090810

Device Name: Thermo Scientific Cyto-Cal™ Count Tubes

Indication For Use:

Thermo Scientific Cyto-Cal™ Count Tubes are used for determining absolute counts of leucocytes in blood.

Thermo Scientific Cyto-Cal™ Count Tubes are used with the immnuphenotyping reagents BD TriTEST™, flow cytometers BD FACS Calibur or BD FACS Canto, and software BD CellQuest or DIVA. Thermo Scientific Cyto-Cal™ Count Tubes can be used with the BD FACS™ Loader.

This in vitro diagnostic device is intended for clinical use only.

Prescription Use _ X

And/Or

Over the Counter Use

(21 CFR Part 801 Subpart D) Subpart C)

(21 CFR Part 801

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Sunt K

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K090810

Regulation Number and Section

§ 864.5220 Automated differential cell counter.

(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”