Predicate Devices

Reference Devices

Not Found.

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary mentions "computer imaging" and "image-based assessment of cell morphology," but it does not explicitly mention AI, ML, or related terms like deep learning or neural networks. While image processing is a component often used with AI/ML in this domain, its presence alone is not sufficient to confirm the use of AI/ML based on this summary. The "Mentions AI, DNN, or ML" field is also marked as "Not Found".

Therapeutic

No
The device is an in vitro diagnostic (IVD) device used for analyzing blood samples and providing imaging of blood cell morphology. It is used to generate data for diagnosis, not to treat a condition.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" explicitly states that the device is "intended for in vitro diagnostic use by a skilled operator in the clinical laboratory." The device performs a complete blood count and analyzes cell morphology, which are diagnostic procedures.

SaMD (Software as a Medical Device)

No

The device description explicitly states it is a "fully automated stand-alone hematology analyzer with integrated slide making capability and digital cell imaging," indicating it is a hardware device with integrated software, not a software-only medical device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "It is intended for in vitro diagnostic use by a skilled operator in the clinical laboratory."
Function: The device analyzes whole blood samples to provide quantitative measurements and morphological assessments of blood cells. This is a classic function of an in vitro diagnostic device, as it is performed on a sample taken from the body (in vitro) to aid in diagnosis or monitoring.
Clinical Laboratory Setting: The intended user and setting are the clinical laboratory, which is where IVD testing is performed.
Parameters Reported: The reported parameters (RBC, WBC, HGB, etc.) are standard hematology parameters used in clinical diagnosis and monitoring.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The cobas m 511 integrated hematology analyzer is a quantitative, automated analyzer with cell locating capability. It is intended for in vitro diagnostic use by a skilled operator in the clinical laboratory. The system prepares a stained microscope slide from EDTA-anticoagulated whole blood. It utilizes computer imaging to count the formed elements of blood and provide an image-based assessment of cell morphology, which may be reviewed by the operator, and also allows for manual classification of unclassified cells. The instrument reports the following parameters: RBC, HGB, HCT, MCV, MCH, MCHC, RDW, RDW-SD, %NRBC, #NRBC, WBC, %NEUT, #NEUT, %LYMPH, #LYMPH, %MONO, #MONO, %EO, #EO, %BASO, #BASO, PLT, MPV, %RET, #RET, HGB-RET.

Product codes

GKZ, JOY

Device Description

The cobas m 511 system is a fully automated stand-alone hematology analyzer with integrated slide making capability and digital cell imaging. It provides a complete blood count, 5-part differential, and reticulocyte enumeration of samples of whole blood collected in K2 or K3 EDTA. It is designed for high throughput in the clinical laboratory environment.

Mentions image processing

Yes

Mentions AI, DNN, or ML

Not Found.

Input Imaging Modality

Digital morphology from an automatically produced Romanowsky stained monolayer slide. Images captured at low magnification (10x lens) and high magnification (50x lens).

Anatomical Site

Blood (formed elements of blood)

Indicated Patient Age Range

Normal healthy donors for adult males, adult females, and the following six (6) pediatric subgroups: 0 to

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.”

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

March 2, 2018

Roche Diagnostics Hematology, Inc. Dan Bracco Head of Clinical and Regulatory Affairs 69 Milk Street, Suite 120 Westborough, Massachusetts 01581

Re: K171655

Trade/Device Name: cobas m 511 integrated hematology analyzer Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ, JOY Dated: June 2, 2017 Received: June 5, 2017

Dear Dan Bracco:

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Leonthena R. Carrington -S

Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K171655

Device Name

cobas m 511 integrated hematology analyzer

Indications for Use (Describe)

The cobas m 511 integrated hematology analyzer is a quantitative, automated analyzer with cell locating capability. It is intended for in vitro diagnostic use by a skilled operator in the clinical laboratory. The system prepares a stained microscope slide from EDTA-anticoagulated whole blood. It utilizes computer imaging to count the formed elements of blood and provide an image-based assessment of cell morphology, which may be reviewed by the operator, and also allows for manual classification of unclassified cells. The instrument reports the following parameters: RBC, HGB, HCT, MCV, MCH, MCHC, RDW, RDW-SD, %NRBC, #NRBC, WBC, %NEUT, %LYMPH, #LYMPH, %MONO, #MONO, %EO, #EO, %BASO, #BASO, PLT, MPV, %RET, #RET, HGB-RET.

Type of Use (Select one or both, as applicable)
Registration Use (Part 21 CFR 601 Subpart D) One-Time Study Use (21 CFR 601 Subpart C)	Registration Use (Part 21 CFR 601 Subpart D)	One-Time Study Use (21 CFR 601 Subpart C)
Registration Use (Part 21 CFR 601 Subpart D)
One-Time Study Use (21 CFR 601 Subpart C)

Prescription Use (Part 21 CFR 801 Subpart D)

| | Over-The-Counter Use (21 CFR 801 Subpart C)

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cobas m 511 integrated hematology analyzer 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

In accordance with 21 CFR 807.87, Roche Diagnostics Hematology, Inc. (RDH) hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).

The purpose of this traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the cobas m 511 integrated hematology analyzer (cobas m 511 system).

Submitter Name	Roche Diagnostics Hematology, Inc.
Address	69 Milk Street
Suite 120
Westborough, MA 01581
Contact	Dan Bracco
Phone: (508) 329-2455
FAX: (508) 329-2486
Email: dan.bracco@roche.com
Date Prepared	February 22, 2018
Proprietary Name	cobas m 511 integrated hematology analyzer
Common Name	Automated Differential Cell Counter
Automated Cell Locating Device
Classification Name	21 CFR 864.5220, Differential Cell Counter, Class II
21 CFR 864.5260, Automated Cell Locating Device, Class II
Product Codes,
Regulation Numbers	GKZ
JOY
Predicate Devices	Sysmex® XN-Series (XN-10, XN-20) Automated Hematology Analyzer
CellaVision® DM1200 Automated Hematology Analyzer
Establishment Registration	The establishment registration number for Roche Diagnostics Hematology has
not yet been established.

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1. DEVICE DESCRIPTION

The cobas m 511 system is a fully automated stand-alone hematology analyzer with integrated slide making capability and digital cell imaging. It provides a complete blood count, 5-part differential, and reticulocvte enumeration of samples of whole blood collected in K2 or K3 EDTA. It is designed for high throughput in the clinical laboratory environment.

Instrument Components and Consumables 1.1.

The cobas m 511 system consists of the following major components:

The analyzer, with rack transport system for sample tubes .
Viewing stations, that can be configured as the control station or as a review station .
Associated consumables and components .

The cobas m 511 system major components:

cobas m 511 analyzer 1.1.1. -

The cobas m 511 analyzer is a stand-alone hematology analyzer with integrated slide making capability and digital cell imaging. It has five (5) processing stations: sample mixing, slide printing, slide staining, slide imaging (low and high magnification), and slide output. It also includes a separate compartment, which houses the necessary consumables and waste containers.

cobas m 511 viewing station 1.1.2. -

The viewing station hardware is a computer with custom software developed by RDH that provides the graphical user interface for the system. It is designed to interface with a standard Laboratory Information System (LIS) for results reporting.

DigiMAC3 stain pack 1.1.3. -

The DigiMAC3 stain pack is intended to fix and stain cells from a whole blood sample or control/calibrator material that have been applied to a slide by the cobas m 511 analyzer, in order to make the cells suitable for automated imaging or manual microscopy. The DigiMAC3 stain pack is comprised of the following four (4) separate solutions, which are individually applied to each processed slide: DigiMAC3 fix, DigiMAC3 eosin, DigiMAC3 methylene blue,

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and DigiMAC3 rinse. The application of these stain solutions results in a Romanowsky type stain such as typically used in hematologic evaluations of whole blood.

DigiMAC3 reticulocyte 1.1.4. -

DigiMAC3 reticulocyte is intended to stain a whole blood sample or control material before it is applied to a slide by the cobas m 511 analyzer, in order to make the reticulocytes suitable for automated imaging or manual microscopy. DigiMAC3 reticulocyte is a supravital stain consisting of an aqueous solution of Azure B dye as the critical component, which condenses the reticulum in red blood cells and allows visualization of reticulocytes. Unlike the stain pack solutions that stain a prepared slide, DigiMAC3 reticulocyte is mixed with the whole blood sample by the cobas m 511 analyzer prior to slide printing.

DigiMAC³ wash 1.1.5. -

DigiMAC3 wash is used to clean all specimen-contacting surfaces, including blood fluid pathways, following processing of each blood sample. This solution is unique to the cobas m 511 system and is comprised of detergent and preservative in an aqueous, buffered solution.

1.1.6. DigiMAC³ clean

DigiMAC3 clean is primarily a 0.7% sodium hypochlorite formulation, which is used to remove protein build-up from the surfaces of the cobas m 511 analyzer components that come in contact with blood samples.

DigiMAC3 slides 1.1.7.

The DigiMAC3 slide is a glass substrate on which a whole blood sample or control/calibrator material is applied and stained by the cobas m 511 analyzer, in order to enable automated imaging or manual microscopy.

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Principles of Operation 1.2.

The cobas m 511 system uses digital morphology from an automatically produced Romanowsky stained monolayer slide, to provide the standard set of hematology parameters for the complete blood count (CBC), automated white blood cell (WBC) differential, and the enumeration of reticulocytes. This is done through the use of proprietary imaging algorithms that locate, count and evaluate red and white blood cells, platelets and nucleated red blood cells.

The cobas m 511 system prints a consistent sample volume (a nominal 1 uL) onto a glass microscope slide using a precision application method. In the stainer module, four reagents are applied to the cells on the slide: a fixative, an eosin stain, a methylene blue stain, and a rinse. Following staining, the slide is imaged at low magnification using a 10x lens to locate, image, and count white and red blood cells, nucleated red blood cells, and platelets. The system selects a specific number of white blood cell locations and provides their coordinates to the high magnification module for additional analysis. In the high magnification module a 50x lens is used to classify white blood cell types, evaluate red blood cells, and platelets and to evaluate cellular morphology. The white blood cells are categorized into the five (5) normal types or as unclassified cells by the instrument. This allows a skilled technologist to review images of the cells on the viewing station or to perform a full microscopic review of the slide. This 50x magnification is also used to identify and count the reticulocytes when a reticulocyte test is requested. For reticulocyte processing, an additional slide is produced from blood in the sample cup that is first incubated with a supravital stain. The cells are then printed onto the slide, stained using DigiMAC3 stain and imaged to determine the number and percentage of reticulocytes and reticulocyte hemoglobin.

Following processing, results and images can be viewed on the viewing station. The viewing station allows the operator to monitor system processes and status, and to view sample processing and results. The viewing station also allows a skilled medical technologist to perform a full white blood cell differential and a morphological review of white blood cells, red blood cells and platelets for samples requiring further review.

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1.3. -Modes of Operation

Closed-tube (automated rack) mode .
Open-tube (manual) mode .

Specimen Identification 1.4.

Specimen identification is performed automatically by the cobas m 511 system through an integrated barcode reader; or manually by the operator through the use of a hand-held barcode reader or keypad.

Specimen Sampling and Handling 1.5.

Samples can be introduced onto the cobas m 511 system using either the closed-tube (automated rack mode) or open-tube modes. In the closed-tube mode the sample tubes into a custom rack. The rack is then mechanically transported into the cobas m 511 system for processing. In this mode the cobas m 511 system automatically mixes, aspirates, and analyzes samples while the sample caps remain intact. In the open-tube mode, the operator mixes the samples tubes individually by hand and then introduces the sample to the open-port aspiration probe presented by the cobas m 511 system. The operator will position the tube such that the aspiration probe is immersed into the approximate center of the blood volume.

1.6. Calibration

The DigiMAC3 calibrator is used for calibration of the cobas m 511 system. The calibrator is a stable suspension of cells of human or animal origin. It is used for calibrating the following hematology parameters of the cobas m 511 system: WBC, RBC, MCH, MCV, PLT, and MPV.

Quality Control 1.7.

DigiMAC3 controls are used to monitor the performance of the cobas m 511 system. These hematology quality control (OC) materials consist of stable suspensions of cells of human or animal origin. They are used for evaluating the accuracy and precision of all hematology parameters of the cobas m 511 analyzer. There are three (3) levels of controls (11, L2 and L3), which are used in conjunction with each other for monitoring the performance of the cobas m 511 analyzer.

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1.8. Software

FDA has reviewed applicant's Hazard Analysis and Software Development processes for this line of product types: Yes

INTENDED USE 2.

Indication(s) for Use 2.1.

The cobas m 511 integrated hematology analyzer is a quantitative, automated analyzer with cell locating capability. It is intended for in vitro diagnostic use by a skilled operator in the clinical laboratory. The system prepares a stained microscope slide from EDTA-anticoagulated whole blood. It utilizes computer imaging to count the formed elements of blood and provide an imagebased assessment of cell morphology, which may be reviewed by the operator, and also allows for manual classification of unclassified cells. The instrument reports the following parameters: RBC, HGB, HCT, MCV, MCH, MCHC, RDW, RDW-SD, %NRBC, #NRBC, WBC, %NEUT, #NEUT, %LYMPH, #LYMPH, %MONO, #MONO, %EO, #EO, %BASO, #BASO, PLT, MPV, %RET, #RET, HGB-RET.

2.2. Special Conditions for Use Statement(s):

For prescription use only

SUBSTANTIAL EQUIVALANCE INFORMATION 3.

Predicate Device Names(s) and 510(k) numbers 3.1.

Sysmex® XN-Series (XN-10, XN-20) Automated Hematology Analyzer (Sysmex Analyzer) -K112605

CellaVision® DM1200 Automated Hematology Analyzer (CellaVision Analyzer) – K092868

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3.2. Comparison with Predicate Device

Table 1 compares the cobas m 511 system with its predicate device.

ltem	Submitted Device:	Predicate Device:
Indications for use	cobas m 511 system
The cobas m 511 integrated hematology
analyzer is a quantitative, automated
analyzer with cell locating capability. It is
intended for in vitro diagnostic use by a
skilled operator in the clinical laboratory.
The system prepares a stained
microscope slide from EDTA-
anticoagulated whole blood. It utilizes
computer imaging to count the formed
elements of blood and provide an image-
based assessment of cell morphology,
which may be reviewed by the operator,
and also allows for manual classification of IRF, RET-He and has a Body Fluid mode
unclassified cells. The instrument reports
the following parameters: RBC, HGB,
HCT, MCV, MCH, MCHC, RDW, RDW-
SD, %NRBC, #NRBC, WBC, %NEUT,
#NEUT, %LYMPH, #LYMPH, %MONO,
#MONO, %EO, #EO, %BASO, #BASO,
PLT, MPV, %RET, #RET, HGB-RET.	Sysmex Analyzer
The XN-Series modules (XN-10, XN-20)
are quantitative multi-parameter automated
hematology analyzers intended for in vitro
diagnostic use in screening patient
populations found in clinical laboratories.
The XN-Series modules classify and
enumerate the following parameters in
whole blood: WBC, RBC, HGB, HCT,MCV,
MCH, MCHC, PLT (PLT-I, PLT-F),
NEUT%/#, LYMPH%/#, MONO%/#,
E0%/#, BASO%/#, IG%/#, RDW-CV,
RDW-SD, MPV, NRBC%/#, RET%/#, IPF,
for body fluids. The Body Fluid mode
enumerates the WBC-BF, RBC-BF,
MN%/#, PMN%/#, and TC-BF# parameters
in cerebrospinal fluid (CSF),serous fluids
(peritoneal, pleural) and synovial fluids.
Whole blood should be collected in K2 or K3
EDTA anticoagulant and, Serous and
Synovial fluids in K2 EDTA anticoagulant to
prevent clotting of fluid. The use of
		anticoagulants with CSF specimens is
neither required nor recommended.
Conditions for use	For prescription use.	Same
Principle of operation	Characterizes and identifies cells using
digital imaging of stained cells on a
microscope slide.	Characterizes and identifies cells based
on detection of direct-current resistance
light scatter, fluorescence, and adaptive
cluster analysis.
	Low magnification location and imaging of
white and red blood cells and platelets
using a 10x objective, combined with
illumination optics and a camera.
High magnification imaging of white blood
cell types and cell morphology using a 50x
objective, combined with illumination optics
and a camera.	Flow cytometry method using a
semiconductor laser to analyze
physiological and chemical characteristics
of cells and other biological particles
Hydro Dynamic Focusing (DC Detection)
with aperture to count the RBC and PLT
and calculate the HCT via the RBC pulse
height detection method.
	Hemoglobin measurement using LED light
absorption	SLS-Hemoglobin Method using
hemoglobin absorption after chemical
lysing and LED light.
Item	Submitted Device:
cobas m 511 system	Predicate Device:
Sysmex Analyzer
	Automatically classifies cells from whole
blood and carries out all processes from
aspiration of sample to outputting of
results.	Automatically classifies cells from whole
blood and carries out all processes
automatically from aspiration of the sample
to outputting of results.
	Displays analysis results and graphics on
a computer screen.	Same
	Results can be printed on available printer
or transmitted to a host computer.	Same
Modes of operation	Closed-tube (automated rack) mode
Open-tube (manual) mode	Sampler Analysis Mode (Closed Cap)
Manual Analysis Mode (Closed and Open
Cap)
Pre-dilute Analysis Mode
Low WBC Analysis Mode
Body Fluid Mode
Methodology	Performs automated analyses of whole
blood cells using a combination of low and
high magnification computer imaging of
stained cells.	Performs hematology analyses according
to the Hydro Dynamic Focusing (DC
Detection), flow cytometry method (using
semiconductor laser), and SLS-hemoglobin
method.
Sample identification	Automated barcode reading of sample tube
identifier.
Manual keyboard entry.
Bi-directional instrument to LIS interface:
patient demographics, orders, results.	Same
Calibrator	Calibration and verification of calibration
using stabilized whole blood calibrator.	Same
	DigiMAC³ calibrator	XN CAL (for WBC, RBC, HGB, HCT, PLT
and RET)
XN CAL PF (for PLT-F)
Quality control	Three (3) stabilized whole blood control
levels of varying component
concentrations.	Same
	DigiMAC³ control L1
DigiMAC³ control L2
DigiMAC³ control L3	XN Check (3 levels)
Sample types	Whole blood	Same
Body Fluids
Anticoagulant	K2 and K3 ethylenediaminetetraacetic acid
(EDTA)	Same
Sample collection device	Evacuated blood collection tube containing
EDTA as an anticoagulant.	Same
Quality control
techniques	Levey-Jennings control chart
X-bar charting	Same
Item	Submitted Device:
cobas m 511 system	Predicate Device:
Sysmex Analyzer
Intended use population	All whole blood samples from any
individual sent to laboratory for analysis.	Same, also including body fluids
Sample aspiration
volume	30µL (closed-tube and open-tube mode)	88µL (Sampler Mode-Whole Blood)
88µL (Manual Mode- Whole Blood)
70µL (Manual Mode- Diluted Blood)
Service diagnostics	On-board system diagnostics
Manufacturer can perform web-based
diagnostics.	Same
Throughput	Approximately 60 samples/hour maximum	Approximately 100 samples/hour maximum
Reagents	DigiMAC3 stain pack, including:
DigiMAC3 fix (fixative)
DigiMAC3 eosin (stain)
DigiMAC3 methylene blue (stain)
DigiMAC3 rinse (rinse)
DigiMAC3 reticulocyte (stain)	CELLPACK DCL (Diluent)
CELLPACK DFL (Diluent)
LYSERCELL WNR (Lyse)
LYSERCELL WDF (Lyse)
LYSERCELL WPC (Lyse)
FLUOROCELL WNR (Stain)
FLUOROCELL WDF (Stain)
FLUOROCELL RET (Stain)
FLUOROCELL PLT (Stain)
FLUOROCELL WPC (Stain)
SULFOLYSER (Lyse)
Cleaning solutions	DigiMAC3 wash
DigiMAC3 clean	CELLCLEAN AUTO
Software	Analyzer OS: Linux
Viewing Station OS: MacOS	Microsoft Windows
	Proprietary cobas m 511 software	Proprietary Sysmex software
Analysis technique	Instrument measures targeted parameters
automatically.
Examiner can assess results via viewing
screen or printed report.	Same
Number of samples	Multiple maintained in queue.
One sample result presented at a time.	Same
Number of individuals
represented per sample	One	Same
Presentation of
abnormal samples	Results reported numerically with flags.	Same
Analyte targets	Components of cells such as DNA, RNA
and proteins	Same
Sample preparation
procedure	Printing of blood onto a microscope slide
followed by staining of the slide.	Flow analysis after dilution and mixing with
reagents.
Light sources	Light Emitting Diodes (LEDs)	Semiconductor Laser
Operational conditions	18 to 27°C ambient temperature
20-60% relative humidity	15 to 30°C ambient temperature
20-85% relative humidity
ltem	Submitted Device:
cobas m 511 system	Predicate Device:
Sysmex Analyzer
Automation	Transportation of racks of sample tubes on
conveyor.	Same
Sample handling system	Individual sample tubes are automatically
removed from rack to be processed.
Manual open-tube mode.	Same
Reagent access	Reagent (cleaning solution) and slides
stored within the instrument and remaining
reagents stored in a drawer within the
instrument below the analytical
components.	Reagents stored within the top front cover
of the instrument and in a cabinet below the
analyzer.
Reagent bottle/Cartridge
identification	Barcodes	Barcode or reagent specific cassette
position
Reagent mixing	No reagent mixing required.	Same
Information transfer to
and from instrument	Through LIS or manual entry on a computer
screen.	Same
Probe cleaning	Automatically for each specimen and
periodically with special clean reagent.	Same
Host interface	LIS or middleware	Same
Calibration intervals	Performed by manufacturer at installation
and as needed.	Same
Stain types	Absorbent dyes, hemoglobin absorption
with LED light.	Fluorescent dyes, hemoglobin absorption
with chemical lysing and semiconductor
laser beam light.
User management	Allows setting of user assignment and
level of access.	Same
Flagging of errors or
sample conditions	System and sample errors and messages
are configurable, displayed and reported
by system to the LIS.	Same

Table 1: Comparison with Predicate Device

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Table 2 compares the cobas m 511 system with its predicate device, CellaVision Analyzer.

| Item | Submitted Device:
cobas m 511 system | Predicate Device:
CellaVision Analyzer |
|--------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for use | The cobas m 511 integrated hematology
analyzer is a quantitative, automated
analyzer with cell locating capability. It is
intended for in vitro diagnostic use by a
skilled operator in the clinical laboratory.
The system prepares a stained
microscope slide from EDTA-
anticoagulated whole blood. It utilizes
computer imaging to count the formed
elements of blood and provide an image-
based assessment of cell morphology,
which may be reviewed by the operator,
and also allows for manual classification
of unclassified cells. The instrument
reports the following parameters: RBC,
HGB, HCT, MCV, MCH, MCHC, RDW,
RDW-SD, %NRBC, #NRBC, WBC,
%NEUT, #NEUT, %LYMPH, #LYMPH,
%MONO, #MONO, %EO, #EO, %BASO,
#BASO, PLT, MPV, %RET, #RET, HGB-
RET. | DM1200 is an automated cell-locating
device. DM1200 automatically locates and
presents images of blood cells on
peripheral blood smears. The operator
identifies and verifies the suggested
classification of each cell according to type.
DM1200 is intended to be used by skilled
operators, trained in the use of the device
and in recognition of blood cells. |
| Principle of operation | Low magnification location and imaging of
white and red blood cells and platelets.
High magnification imaging of white blood
cell types and cell morphology.
Displays analysis results, graphics, and
images on a computer screen.
Results can be printed on available printer
or transmitted to a host computer. | The analysis process consists of an
overview image processing and a cell-
location step. The overview image is used to
find cells of interest and to obtain an overall
impression of the sample. The overview
image can have one 10x zoom level or both
10x and 50x zoom levels. The cell-location
step uses the optical unit and a camera to
obtain images of the identified images and
stores the images in a database. |
| Methodology | Performs automated analyses of whole
blood cells using a combination of low and
high magnification imaging of stained cells
on a glass microscope slide, with
subsequent operator review of
computerized images or glass microscope
slide for flagged cases. | Same |
| Sample identification | Automated barcode reading of sample
identifier.
Manual keyboard entry. | Same |
| Specimen types | Whole Blood | Same
Body Fluids |
| Item | Submitted Device:
cobas m 511 system | Predicate Device:
CellaVision Analyzer |
| Sample preparation | Automated slide preparation and staining. | Automated or manual slide preparation and staining. |
| Stains | Romanowsky type stain | Same |
| Analysis technique | Locates, identifies, and counts the various
types of white blood cells under the
automated microscope.
Red blood cells and platelets and platelet
morphology can be assessed by examiner. | Same |
| Presentation of samples | Results reported numerically.
Cells can be observed on a computer
display.
Cells can be observed through a
microscope. | Same |
| Handling of abnormal
samples | Images automatically made available for
review.
Slides available as needed for subsequent
review. | Same |
| Analyte targets | Stained components of cells such as DNA,
RNA, and proteins. | Same |
| Light sources and
detector | LED light sources with specific Blue,
Green, Yellow and Red wavelengths.

Black and White cameras. | White light source.

Comparison with CellaVision Analyzer Table 2:

14

15

4. SPECIAL CONTROL/GUIDANCE DOCUMENT REFERENCED (IF APPLICABLE)

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

| CLSI EP05-A3 | Evaluation of Precision of Quantitative Measurement Procedures;
Approved Guideline - Third Edition |
|------------------|-----------------------------------------------------------------------------------------------------------------------------|
| CLSI EP06-A | Evaluation of the Linearity of Quantitative Measurement Procedures:
A Statistical Approach; Approved Guideline |
| CLSI EP07-A2 | Interference Testing In Clinical Chemistry; Approved Guideline -
Second Edition |
| CLSI EP09-A3 | Measurement Procedure Comparison and Bias Estimation Using
Patient Samples; Approved Guideline - Third Edition |
| CLSI EP10-A3-AMD | Preliminary Evaluation of Quantitative Clinical Laboratory
Measurement Procedures, Approved Guideline - Third Edition |
| CLSI EP17-A2 | Evaluation of Detection Capability for Clinical Laboratory Measuremen
Procedures; Approved Guideline - Second Edition |
| CLSI EP28-A3c | Defining, Establishing, and Verifying Reference Intervals in the
Clinical Laboratory: Approved Guideline - Third Edition |

16

CLSI H20-A2 Reference Leukocyte (WBC) Differential Count (Proportional) and Evaluation of Instrumental Methods: Approved Standard -Second Edition
Validation, Verification, and Quality Assurance of Automated CLSI H26-A2 Hematology Analyzers; Approved Standard - Second Edition
Safety requirements for electrical equipment for measurement, control, IEC 61010-1:2010 and laboratory use - Part 1: General requirements
IEC 61010-2-101:2015 Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment
IEC 61326-1:2012 Electrical equipment for measurement, control and laboratory use -EMC requirements - Part 1: General requirements
IEC 61326-2-6:2012 Electrical equipment for measurement, control and laboratory use -EMC requirements - Part 2-6: Particular requirements - In vitro diagnostic (IVD) medical equipment
IEC 62304:2006 Medical device software - Software life cycle processes
ISO 14971:2007 Medical devices – Application of risk management to medical devices

17

PERFORMANCE CHARACTERESTICS 5.

Analytical Performance 5.1.

Method Comparison 5.1.1.

A method comparison study was performed to compare results of residual whole blood samples that were randomly collected for a minimum of two (2) weeks at each of four (4) clinical sites. Specific interference samples and medical decision level samples were also included at each site. Each sample was processed on the cobas m 511 system and the predicate device within eight (8) hours of venipuncture. Correlation and bias between the cobas m 511 system and the comparator analyzer were determined in accordance with the CLSI EP09-A3 guideline based on the results of either a Passing-Bablok or Deming regression model. For the %NRBC and #NRBC parameters the mean difference was used to calculate bias in accordance with the CLSI EP09-A3 guideline. If a parameter has mixed acceptance criteria comprised of both an absolute bias limit and a proportional bias limit, the bias been reported at the crossover point where the two (2) bias limits are equal. In these cases the crossover point is listed in both absolute and proportional terms for the same value. Because bias is calculated using a linear model, if the calculated bias was found to be acceptable at the low bias limit, high bias limit, and crossover point (if required), the bias is considered acceptable at all points in between. The results of the Method Comparison evaluation were found to be acceptable for all reportable parameters. The results for all sites combined are shown in Table 3.

18

| Parameter
[Units] | N | Pearson's
(r) | Intercept
(95% CI) | Slope (95% CI) Range | Evaluation Range | Limit |
|----------------------|----- | WBC
[103/µL] | 1859 | 0.999 (-0.01, 0.05) | 1.012
(1.007, 1.017) | (0.04, 247.04) | 0.50 (0.00, 0.05) | 0.07
(0.05, 0.08)
[103/µL] | 1.7
(1.34, 2.09)
[%] | 1.26
(0.87, 1.69) |
| RBC
[106/µL] | 1859 | 0.974 (-0.01, 0.04) | 0.991
(0.985, 1.000) | (1.15, 7.21) (-0.59, -0.25) | N/A (-0.82, -0.18) |
| HGB
[g/dL] | 1853 | 0.970 (-0.41, -0.24) | 1.046
(1.039, 1.053) | (4.20, 21.20) | 4.50 (-0.17, -0.07) | 0.14
(0.11, 0.15)
[g/dL] | 1.35
(1.15, 1.53)
[%] | 3.08
(2.70, 3.42) |
| HCT [%] | 1859 | 0.953 (-1.06, -0.35) | 1.043
(1.033, 1.053) | (13.50, 66.00) | 14.00 (-2.40, 0.71) | N/A (2.68, 3.68) |
| MCV [fL] | 1859 | 0.887 (-5.06, -0.87) | 1.060
(1.035, 1.083) | (58.20, 119.20) | 80.00 (1.97, 2.58) | N/A (2.65, 3.36) |
| MCH
[pg] | 1844 | 0.956 (0.73, 1.80) | 0.974
(0.960, 0.996) | (17.58, 40.75) | 28.00 (2.14, 2.52) | N/A (1.19, 1.76) |
| MCHC
[g/dL] | 1844 | 0.559 (14.73, 16.45) | 0.522
(0.500, 0.552) | (26.59, 36.80) | 32.00 (1.09, 1.43) | N/A (-4.44, -3.92) |
| RDW [%] | 1859 | 0.913 (2.15, 2.74) | 0.870
(0.848, 0.892) | (10.70, 29.40) | 12.00 (6.98, 7.86) | N/A (3.39, 4.11) |
| RDW-SD
[fL] | 1859 | 0.912 (4.48, 6.46) | 0.940
(0.917, 0.963) | (31.70, 97.10) | 40.00 (7.31, 8.13) | N/A (2.42, 3.90) |
| PLT [103/µL] (-13.21, -8.94) | 1.020
(1.008, 1.031) | (1.00, 1061.00) | 10.00 (-12.94, -8.85) | -9.54
(-11.04, -8.10)
[103/µL] | -12.73
(-14.72, -10.80) [%] | 0.88
(-0.08, 1.84) |
| MPV [fL] | 1678 | 0.772 (-1.40, -0.20) | 1.063
(1.000, 1.111) | (8.00, 13.00) | 8.00 (-6.62, -2.50) | N/A (-3.03, -1.96) |
| | | | Parameter
[Units] | N | Pearson's
(r) | Intercept
(95% CI) | Slope (95% CI) Range | Low
End | Crossover
Point | High
End | At Low Limit Limit |
| %NRBC
[/100 WBC] | 1862 | 0.981 (-0.06, 0.01) | N/A difference) |
| #NRBC
[103/µL] | 1864 | 0.995 (0.00, 0.00) | N/A difference) |
| %NEUT [%] | 1585 | 0.989 (1.12, 2.15) | 1.012
(1.004, 1.019) | (10.10, 94.00) | 40.00 (4.60, 5.84) | N/A (2.82, 3.30) |
| %LYMPH
[%] | 1648 | 0.989 (-0.37, -0.08) | 0.977
(0.971, 0.983) | (0.70, 83.00) (-0.91, -0.70) | -1.15
(-1.32, -0.98)
[%LYMPH] | -2.89
(-3.30, -2.44)
[%] | -2.66
(-3.13, -2.15) |
| %MONO
[%] | 1648 | 0.913 (-0.82, -0.50) | 1.000
(1.000, 1.026) | (0.60, 24.50) | 2.00 (-0.78, -0.50) | N/A (-0.70, -0.50) |
| %EO [%] | 1702 | 0.973 (-0.13, -0.03) | 1.042
(1.030, 1.054) | (0.00, 32.90) | 0.00 (-0.13, -0.03) | N/A (0.09, 0.17) |
| %BASO [%] | 1788 | 0.721 (-0.35, -0.25) | 1.649
(1.576, 1.723) | (0.00, 3.10) (-0.35, -0.25) | N/A (0.31, 0.39) |
| #NEUT
[103/µL] | 1585 | 0.994 (0.09, 0.15) | 1.027
(1.021, 1.033) | (0.37, 37.66) | 1.00 (0.12, 0.17) | 0.16
(0.14, 0.19)
[103/µL] | 10.98
(9.18, 12.37)
[%] | 3.92
(3.43, 4.36) |
| #LYMPH
[103/µL] | 1648 | 0.990 (-0.07, -0.05) | 1.032
(1.022, 1.042) | (0.02, 12.66) | 0.50 (-0.05, -0.03) | -0.01
(-0.02, 0.00)
[103/µL] | -0.71
(-1.30, -0.16)
[%] | 1.26
(0.58, 1.87) |
| #MONO
[103/µL] | 1648 | 0.940 (-0.04, -0.02) | 1.000
(0.976, 1.000) | (0.01, 6.14) (-0.04, -0.02) | N/A (-0.06, -0.03) |
| #EO
[103/µL] | 1702 | 0.976 (-0.01, 0.00) | 1.071
(1.060, 1.083) | (0.00, 7.17) (-0.01, 0.00) | N/A (0.03, 0.04) |
| #BASO
[103/µL] | 1788 | 0.680 (-0.03, -0.02) | 1.661
(1.577, 1.744) | (0.00, 0.46) (-0.03, -0.02) | N/A (0.04, 0.05) |
| %RET [%] | 1842 | 0.964 (-0.39, -0.32) | 1.094
(1.072, 1.116) | (0.05, 12.93) | 0.50 (-0.34, -0.28) | -0.20
(-0.21, -0.18)
[%RET] | -11.91
(-12.75, -10.83) [%] | -4.84
(-5.80, -3.81) |
| Parameter
[Units] | N | Pearson's
(r) | Intercept
(95% CI) | Slope (95% CI) Range | Evaluation Range | | | | | #RET
[106/µL] | 1834 | 0.924 (-0.01, -0.01) | 1.070
(1.047, 1.092) | (0.00, 0.42) (-0.01, -0.01) | N/A | HGB-RET
[pg] | 1701 | 0.793 (-4.69, -1.94) | 1.141
(1.100, 1.184) | (16.23, 45.00) | 23.00 (-2.11, 1.61) | N/A | Sample
| | Bias (95% CI) | | | At High
-|------------------|---------------------------|-------------------------|-----------------|------------------|--------------------|-------------|---------------------------|--------------------------------------|--------------------------------|-------------------------|
| 0.02
| 4.00 | 30.00 | 0.03
| 0.02
| 4.00 | N/A | 5.50 | -0.41
| | -0.56
| -0.33
| 10.00 | 21.20 | -0.12
| -0.72
| N/A | 66.00 | -0.87
| | 3.20
| -3.03
| N/A | 100.00 | 2.25
| | 3.01
| 1.37
| N/A | 34.00 | 2.33
| | 1.47
| 15.71
| N/A | 36.00 | 1.26
| | -4.19
| 2.46
| N/A | 14.60 | 7.43
| | 3.78
| 5.48
| N/A | 60.00 | 7.70
| | 3.13
| 1808 | 0.973 | -11.03
| 75.00 | 1000.0 | -10.83
| -0.91
| N/A | 10.20 | -5.08
| | -2.63
| | | | Evaluation Range | | | Bias (95% CI) | | | |
| Sample
| Crossover Point | | At High
| N/A | N/A | (0.00, 186.10) | 0.00 | N/A | 1.50 | -0.03
| | (mean
| N/A | N/A | (0.00, 9.59) | 0.00 | N/A | 0.10 | 0.00
| | (mean
| 1.62
| N/A | 85.00 | 5.21
| | 3.06
| -0.23
| 25.00 | 40.00 | 65.00 | -0.81
| -0.60
| N/A | 10.00 | -0.60
| | -0.60
| -0.08
| N/A | 5.00 | -0.08
| | 0.13
| -0.30
| 0.00 | N/A | 1.00 | -0.30
| | 0.35
| 0.12
| 1.50 | 10.00 | 0.15
| -0.06
| 1.50 | 3.00 | -0.04
| -0.03
| 0.10 | N/A | 1.50 | -0.03
| | -0.03
| -0.01
| 0.00 | N/A | 0.50 | -0.01
| | 0.03
| -0.02
| 0.00 | N/A | 0.10 | -0.02
| | 0.04
| -0.36
| 1.67 | 2.50 | -0.31
| Sample
| | Bias (95% CI) | | | |
| | | | Low End | Crossover Point | High End | At Low Limit | Crossover Point | At High Limit | |
| -0.01
| 0.02 | N/A | 0.15 | -0.01
| 0.00 (0.00, 0.00) | |
| -3.29
| N/A | 40.00 | -0.23
| 5.84 (4.94, 6.83) | |

Table 3: Summary of cobas m 511 system vs. Predicate Device for All Sites Combined

19

20

21

5.1.2. Flaqqing Capabilities

Clinical sensitivity studies were conducted at the four (4) clinical sites to evaluate cobas m 511 system messages (flags) for white blood cells versus a 400-cell reference method. The 400-cell reference method according to the CLSI H20-A2 standard refers to the combined results from two (2) 200-cell WBC differentials performed by individuals on two (2) separate blood smears. The samples used represented a variety of abnormal conditions. The results obtained from comparison of cobas m 511 system messages versus the 400-cell reference method met the acceptance criteria for sensitivity and specificity. These results are summarized in Table 4.

Clinical Sensitivity Analysis – cobas m 511 system Messages for All Sites Table 4: Combined

cobas m 511 system
	Positive (Flagged Abnormal)	Negative (Normal)	Total
Reference Method	Positive (Abnormal)	118	9	127
	Negative (Normal)	10	302	312
Total		128	311	439

Sensitivity = 118/(118+9) x 100% = 92.9%, Specificity = 302/(302+10) x 100% = 96.8%

5.1.3. Precision

Precision studies were performed at the four (4) clinical sites to evaluate repeatability (i.e., within-run precision) when whole blood samples were processed thirty-one (31) consecutive times on the cobas m 511 system, as recommended in the CLSI H26-A2 standard. Residual K2 EDTA whole blood samples spanning the upper and lower limit of the analytical measuring range generally encountered in the laboratory were selected for the WBC, RBC, HGB and PLT parameters. In addition, samples at medical decision levels of anemia, thrombocytopenia, severe leukopenia, and nucleated red blood cells were evaluated. The mean, standard deviation (SD), and coefficient of variation (CV) were calculated for each sample per the CLSI EP05-A3 guideline. Repeatability results met their pre-defined acceptance criteria. The results of the individual assessments by parameter for all sites combined are shown in Table 5.

22

| Parameter
[Units] | Sample Range | Sample Size
(N) | Observations
(N) | Range of
Sample
Means | Mean of
Sample
Means | Repeatability | | |
|-----------------------|-----------------|--------------------|---------------------|-----------------------------|----------------------------|-------------------------|-------------------------|--|
| | | | | | | SD
(95% CI) | %CV
(95% CI) | |
| WBC
[10³/μL] | All | 144 | 4436 | (1.98, 130.75) | 12.06 | 0.233
(0.229, 0.238) | 1.93
(1.89, 1.97) | |
| WBC
[10³/μL] |