(225 days)
ABX PENTRA 80 (K024002)
No
The summary describes a standard automated hematology analyzer with added reticulocyte measurement capabilities using fluorescence detection. There is no mention of AI, ML, or related concepts in the device description, intended use, or performance studies.
No.
The device is an in vitro diagnostic (IVD) device used for analysis of blood samples, not for providing therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the PENTRA XLR is "for in vitro diagnostic use."
No
The device description explicitly states it is a modification to an existing automated hematology analyzer (ABX PENTRA 80) and involves the addition of a "RET mode, based on the use of Thiazol orange reagent and fluorescence detection by optical bench". This indicates the device includes hardware components (optical bench, reagent handling) and is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "for in vitro diagnostic use in clinical laboratories". This is the primary indicator that the device is intended for use outside of the body to examine specimens for diagnostic purposes.
N/A
Intended Use / Indications for Use
The PENTRA XLR is a quantitative multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories to identify and enumerate the following parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, LYM (#, %), MON (#, %), NEU (#, %), EOS (#, %), BAS (#, %), as well as the Reticulocyte parameters RET (#, %), CRC, and IRF in K2EDTA and K3EDTA anticoagulated venous whole blood samples from patients ≥ 18 years of age.
Product codes (comma separated list FDA assigned to the subject device)
GKZ
Device Description
The PENTRA XLR is a device modification to the ABX PENTRA 80 (K024002), which consists in the addition of the measurement of Reticulocytes (RET) parameters to the existing Complete Blood Count (CBC) and Differential (DIFF) counts already performed by the analyzer. The additional RET mode, based on the use of Thiazol orange reagent and fluorescence detection by optical bench, is independent from the modes already existing on the ABX PENTRA 80: the CBC and the CBC+DIFF modes, as there have been no modifications to the existing mechanical and analytical portions of the original device. The existing fundamental scientific technology for the analyzer itself has not changed. Including, hematological parameters for complete blood count and differential leucocyte count, the reagents and controls, measuring principles, and the principles of operation are the same as previously cleared by the FDA. The parameters already available on the ABX PENTRA 80 are unchanged: CBC parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV; DIFF parameters: LYM#, LYM%, MON#, MON%, NEU#, NEU%, EOS#, EOS%, -BAS#, BAS%. The additional Reticulocytes parameters are the following: RET#: Reticulocyte Absolute Value, RET%: Reticulocyte Percentage, CRC: Corrected Reticulocyte Count, IRF: Immature Reticulocyte Fraction. RBC parameter is as well reported in RET mode. Software changes reflect routine updates to the cycle operation, increased user interface options, and the support of the Reticulocyte counting.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
patients ≥ 18 years of age.
Intended User / Care Setting
in clinical laboratories
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Performance
- Analytical Limits at Low Level: Limit of Blank (LoB) and Limit of Detection (LoD) studies performed for RBC parameter. LoB for RBC: 0 x 10^6/mm^3. LoD for RBC: 0.01 x 10^6/mm^3.
- Analytical Sensitivity - Limit of Quantitation (LoQ):
- Reticulocyte parameters: Analytical sensitivity determined using a linearity range. 7 levels prepared and run 4 times each on at least 3 PENTRA XLR instruments with four reagents lots. Analytical sensitivity limits obtained: RET%: 0.7%, RET#: 0.01 x 10^6/mm^3.
- RBC parameter: LoQ determined using linearity ranges. 3 to 6 samples per level prepared and run at least 5 times each (40 replicates per level). LoQ for RBC: 0.24 x 10^6/mm^3.
- Precision (Repeatability): Performed using a minimum of 10 normal and 5 abnormal fresh whole blood samples (K2EDTA) at 3 clinical sites. Each sample run 12 consecutive times. Results were in specifications.
- Precision (Reproducibility): Assessed on four PENTRA XLR instruments at four sites. High, Normal, and Low levels of control material (Minotrol Retic for Reticulocyte parameters, Difftrol for RBC) run in duplicate, twice daily for minimum of 25 days. Results were in specifications.
- Linearity / Assay's Measuring (Reportable) Range: Commercial Linearity kits used. Each level run in replicates of four (n=4). Linear across the claimed range. Claimed AMR: RET%: 0.7 - 27; RET#: 0.01 - 0.5 (10^6/mm^3); RBC: 0.2 - 8.0 (10^6/mm^3).
- Carryover: Tested in duplicate using alternating high and low concentration samples. All carry-over results within specifications. RBC 3 High Level)
RET# (10^6/mm^3) (Normal Level): CV% 0.1 High Level)
CRC (%) (Normal Level): CV% 2.3 High Level)
IRF (Low 0.30 High Level)
RBC (10^6/mm^3): CV% 6 High)
Reproducibility (CV total):
Minotrol Retic Control:
RET% Low Level: 18%, Normal Level: 10%, High Level: 8%
RET# Low Level: 18%, Normal Level: 10%, High Level: 8%
CRC Low Level: 18%, Normal Level: 10%, High Level: 8%
IRF Low Level: 15%, Normal Level: 12%, High Level: 10%
RBC Low Level: 3%, Normal Level: 3%, High Level: 3%
Difftrol Control:
RBC Low Level: 3.0%, Normal Level: 2.5%, High Level: 2.5%
Carry-over Limit:
RBC: 0.95
RET# r2>0.95
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
ABX PENTRA DX 120 (K050719, K991839, K990311)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
ABX PENTRA 80 (K024002)
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.”
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an image of a stylized eagle with three human profiles incorporated into its design. The eagle's wings are formed by the profiles, creating a sense of unity and collaboration.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 9, 2015
HORIBA ABX SAS HORIBA MEDICAL Ms. Caroline Ferrer Regulatory Affairs Manager Parc Euromédecine Rue du Caducée - BP7290 34184 Montpellier Cedex 4, France
Re: K151133
Trade/Device Name: PENTRA XLR Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ Dated: November 6, 2015 Received: November 9, 2015
Dear Ms. Ferrer:
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
1
comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); 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.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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" (21CFR 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 vours.
Leonthena R. Carrington -S
Leonthena R. Carrington, MS, MBA, MT(ASCP) 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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K151133
Device Name PENTRA XLR
Indications for Use (Describe)
The PENTRA XLR is a quantitative multi-parameter automated hematology analyzer for in vitro diagnostic use in clinical laboratories to identify and enumerate the following parameters: WBC, RBC, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, LYM (#, %), MON (#, %), NEU (#, %), EOS (#, %), BAS (#, %), as well as the Reticulocyte parameters RET (#, %), CRC, and IRF in K2EDTA and K3EDTA anticoagulated venous whole blood samples from patients ≥ 18 years of age.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C) |
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Premarket Notification [510(k)] Summarv
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number: K151133
1.0 Sumitted bv : Company: HORIBA ABX SAS HORIBA MEDICAL Parc Euromédecine Rue du Caducée - BP 7290 34184 Montpellier cedex 4 FRANCE
Contact Person: Caroline Ferrer (caroline.ferrer@horiba.com) Telephone: + (33) 4 67 14 1843 Fax: + (33) 4 67 14 1517
2.0 Date Submitted :
November 2, 2015
3.0 Device Name and Classification : Trade/Proprietary Name: PENTRA XLR
Classification:
| Device: | Counter, differential cell |
|---|---|
| Panel: | 81 Hematology |
| Regulation number: | 864.5220 |
| Product Code: | GKZ |
| Class: | II |
4.0 System description : 4.1 Device Description
The PENTRA XLR is a device modification to the ABX PENTRA 80 (K024002), which consists in the addition of the measurement of Reticulocytes (RET) parameters to the existing Complete Blood Count (CBC) and Differential (DIFF) counts already performed by the analyzer.
The additional RET mode, based on the use of Thiazol orange reagent and fluorescence detection by optical bench, is independent from the modes already existing on the ABX PENTRA 80: the
4
CBC and the CBC+DIFF modes, as there have been no modifications to the existing mechanical and analytical portions of the original device.
The existing fundamental scientific technology for the analyzer itself has not changed. Including, hematological parameters for complete blood count and differential leucocyte count, the reagents and controls, measuring principles, and the principles of operation are the same as previously cleared by the FDA. Refer to Table I.
The parameters already available on the ABX PENTRA 80 are unchanged:
- CBC parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV -
- DIFF parameters: LYM#, LYM%, MON%, NEU#, NEU%, EOS#, EOS%, -BAS#, BAS%
The additional Reticulocytes parameters are the following: RET#: Reticulocvte Absolute Value RET%: Reticulocyte Percentage CRC: Corrected Reticulocyte Count IRF: Immature Reticulocyte Fraction
RBC parameter is as well reported in RET mode.
Software changes reflect routine updates to the cycle operation, increased user interface options, and the support of the Reticulocyte counting.
4.2 Principles of Operation
The PENTRA XLR performs hematology analyses using the following methods:
- RBC / PLT: Impedance
- WBC: Impedance ●
- HGB: Spectrophotometry
- DIFF: Impedance with hydrofocus Cytometry and Cytochemistry (DHSS)
- . MCV: Calculated
- . RET: Fluorescence and Impedance
The Principles of Operation for the parameters already existing on the ABX Pentra 80 are unchanged, and are therefore not explained again.
The Principle of Operation for the Reticulocyte Parameters is described below.
The instrument samples 35 uL of blood and injects 10 uL of it in the DIL1 chamber. It then mixes it with 1.7 mL of ABX Diluent. Then the instrument samples 28 uL of diluted blood and mixes it with 2.5 mL of ABX Fluocyte.
This reagent contains a fluorescent stain which is specific to nucleic acids: thiazol orange (Thiazol orange is a patented product from Becton Dickinson, San Jose, CA, USA).
The dilution is warmed at 35°C for 50 seconds. The stain molecules enter through the cell membrane and fix the ribonucleic acid molecules. This binding gives an increase of the
5
fluorescence (enhancement: ~3000x). After 50 seconds, the solution is transferred to the laser optical bench to be measured.
The laser optical bench simultaneously measures the fluorescence of the cells passing through the measuring point into the flowcell, and the volume by impedance. A cell passing through the flowcell gives two types of information:
- The size of the cell measured by resistivity (Cell Impedance Signal),
- The fluorescence signal (Orthogonal Fluorescence Light OFL).
OFL: The fluorescence is collected using:
a lens focused on the optical flowcell and located at 90° from the laser beam,
- an interferential filter specific to the thiazol orange stain selecting only the fluorescent wavelength,
- an avalanche photodiode.
Reticulocvte Matrix:
The Reticulocytes matrix is generated from two measurements: resistivity volume (CIS) and orthogonal fluorescence (OFL) of cells according to the X and Y axes respectively.
Mature red blood cells without RNA show little or no fluorescent signal. They are located at the bottom of the matrix, and horizontally distributed according to their MCV and RDW. Reticulocytes are separated from the red blood cells by their fluorescence which is proportional to the RNA content and their immaturity.
The most fluorescent elements, which are saturated at the top of the matrix, are the most immature. Erythroblasts may also be found in this area.
4.3 Modes of Operation
Measurement modes:
The PENTRA XLR instrument can operate in:
- CBC mode (Complete Blood Count)
- DIFF mode (CBC + WBC Differential)
- RET mode (Reticulocytes + RBC)
Sampling modes:
The PENTRA XLR operates in:
- Automatic sampling (auto mixer and auto loader) for CBC and DIFF modes only ● or
- . Manual sampling (STAT mode) for CBC, DIFF and RET modes.
Therefore, for the RET mode, only the manual sampling (STAT mode) is available.
4.4 Specimen Identification
Tube sample ID can be identified manually or by double barcode label reading.
4.5 Calibration
Calibration is a procedure that is performed during specific situations such as installation, maintenance or service intervention. It is performed by a HORIBA ABX SAS representative. It
6
ensures that the precision and accuracy of the analyzer are acceptable, so that accurate measurements are performed by the analyzer.
The RET measurement is adjusted by HORIBA Medical technician upon the PENTRA XLR installation and according to procedure described in the User Manual.
4.6 Quality Control
Quality control allows the user to monitor a set of analyses based on known sample values and ranges over a period of several months. Statistical computation performed on these populations allows the extraction of qualitative information related to the stability of the instrument. The manufacturer's instructions are to be followed for material and frequency of quality control analysis.
The RET parameters are controlled with a specific Quality Control; ABX MINOTROL RETIC, already cleared by 510(k) K94336 as Retic CONTROL-H Hematology Control, R&D Systems, Inc.
4.7 Software
HORIBA ABX SAS's Hazard Analysis and Software Development process for this product are included in this submission.
5.0 Intended use
5.1 Indications for Use :
The PENTRA XLR is a quantitative multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories to identify and enumerate the following parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, LYM (#, %), MON (#, %), NEU (#, %), EOS (#, %), BAS (#, %), as well as the Reticulocyte parameters RET (#, %), CRC, and IRF in K2EDTA and K3EDTA anticoagulated venous whole blood samples from patients ≥ 18 years of age.
5.2 Special Conditions for Use Statements:
For prescription use only.
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6.0 Comparison with the original device : Similarities
| Item | PENTRA 80 (K024002) Original Device | PENTRA XLR Modified device |
|---|---|---|
| Manufacturer | HORIBA ABX SAS | Same |
| Type of product | Automated blood cell counter | Same |
| Parameters | Complete Blood Cell Count (CBC) | |
| WBC, RBC, HGB, HCT, MCV, MCH, | ||
| MCHC, RDW, PLT, MPV | Same | |
| Leukocyte Differential (DIFF): | ||
| NEU (# and %), LYM (# and %), MON | ||
| (# and %), EOS (# and %), BAS (# and | ||
| %) | Same | |
| Sample types | K2 and K3EDTA anti-coagulated whole | |
| blood | Same | |
| Specimen volume | CBC mode: 35 μL | |
| CBC + DIFF mode: 53 µL | Same | |
| Principles | ||
| of | ||
| measurements | RBC / PLT: Impedance | |
| WBC: Impedance | ||
| HGB: Spectrophotometry | ||
| DIFF: Impedance with hydrofocus | ||
| Cytometry and Cytochemistry (DHSS) | ||
| MCV: Calculated | Same | |
| Reagents | ABX Diluent (10L, 20L) | |
| ABX Cleaner | ||
| ABX Basolyse II | ||
| ABX Eosinofix | Same | |
| Calibrators | ABX Minocal | Same |
| Controls | ABX Minotrol 16 | |
| ABX Difftrol | Same | |
| Throughput | 80 samples / hour | Same |
| Dimensions | ||
| (Height x Width x | ||
| Depth) | 82cm x 57cm x 54cm | Same |
| Performances | ||
| for | ||
| parameters in CBC | ||
| and DIFF modes | Precision | |
| Linearity | ||
| Accuracy | ||
| Leukocyte Differentiation | ||
| Sample stability | Same | |
| Item | PENTRA 80 (K024002) Original Device | PENTRA XLR Modified device |
| Intended Use | The ABX PENTRA 80 Hematology Analyzer is a fully automated (microprocessor controlled) hematology analyzer used for the in vitro diagnostic testing of whole blood specimens. |
The ABX PENTRA 80 is able to operate either in complete blood count (CBC) mode or in CBC + 5 differential leucocyte count (5DIFF) mode. | The PENTRA XLR is a quantitative multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories to identify and enumerate the following parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, LYM#, LYM%, MON#, MON%, NEU#, NEU%, EOS#, EOS%, BAS#, BAS%, as well as the Reticulocyte parameters RET#, RET%, CRC, and IRF in K2EDTA and K3EDTA anticoagulated venous whole blood samples from patients ≥ 18 years of age. |
| RET mode | Not available | Additional Reticulocyte Count (RET):
RET (in #, %), IRF (in %), CRC (in %)
- RBC (same as in CBC mode) |
| Specimen volume in RET mode | No RET Mode | Additional RET mode: 35 μL |
| RET Principles of measurements | No RET Mode | RET: Fluorescence and impedance |
| Hardware | Mechanical and pneumatic | Identical with addition of the following for RET measurement : diode laser, lens focused on the optical flowcell, an interferential filter specific to the thiazol orange stain selecting only the fluorescent wavelength, an avalanche photodiode. |
| Software | Windows-based software application | Identical. The software has been updated to integrate the RET measurement. |
| Reagents | ABX Lyse (ABX Alphalyse or ABX Lysebio) | ABX Lyse (ABX Lysebio only) ABX Fluocyte (specific reagent for Reticulocyte count, based on |
| | | Thiazole Orange dye) |
| Controls | No Reticulocyte Control | ABX Minotrol Retic (specific
control for RET count) |
| Weight | 55 kg | 57 kg |
| Performances | | |
| Reticulocyte
parameter | No Reticulocyte claim | Performance available for RET
(in #, %), IRF (in %), CRC (in %) |
The CBC and DIFF mode performance verification has been done and is on file at HORIBA ABX SAS. The performance of the PENTRA XLR RBC parameter obtained in RET mode has been verified during the RET parameters validation. The RBC parameter performance is identical to the performance obtained in CBC mode and previously detailed to FDA through K024002.
8
Differences
9
SECTION 007 : 510(k) Summary
7.0 Substantial Equivalence Information :
The following tables show the similarities and differences between the candidate device and its predicate device identified below.
7.1 Predicate Device Name and 510(k) number:
For the validation of the Reticulocyte parameters on the PENTRA XLR the following predicate device was used during the clinical evaluation:
| Candidate device | Predicate device | Manufacturer | Predicate 510(k) numbers |
|---|---|---|---|
| PENTRA XLR | ABX PENTRA DX 120 | HORIBA ABX SAS | K050719 |
| K991839 | |||
| K990311 |
7.2 Comparison with predicate Device : Similarities
| Item | ABX PENTRA DX 120 (K991839) Predicate Device for RET parameters | PENTRA XLR Modified device |
|---|---|---|
| Manufacturer | HORIBA ABX SAS | Same |
| Type of product | Automated blood cell counter | Same |
| Diagnostic Parameters | RET: RET (#, %), IRF (%), MRV (Fl), CRC (%), RET L (%), RET M (%), RET H (%) | RET: RET (#, %), IRF (%), CRC (%) |
| Sample types | K2 and K3EDTA anti-coagulated whole blood | Same |
| RET Principles | Fluorescence and Impedance | Same |
| RET Reagents | ABX Fluocyte | Same |
| RET Methodology | ABX Fluocyte contains a fluorescent stain which is specific to nucleic acids: thiazol orange (Thiazol orange is a patented product from Becton Dickinson San | Same |
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SECTION 007 : 510(k) Summary
| Item | ABX PENTRA DX 120 (K991839)
Predicate Device for RET
parameters | PENTRA XLR
Modified device |
|-----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------|
| | Jose, CA, USA).
The stain molecules enter through
the cell membrane and fix the
ribonucleic acid molecules. The
binding gives an increase of
fluorescence. The laser optical
bench simultaneously measures the
fluorescence of the cells passing
through the measuring point into the
flowcell, and volume by
absorbance. The size of the cell is
measured by resistivity, the
scattered light (FSL) is measured
approximately 200 µS after the
aperture measurement, the
fluorescence signal (OFL) is
measured simultaneously with the
FSL. | |
| RET Calibrators | None | Same |
| RET Controls | ABX Minotrol Retic | Same |
| RET Technical
parameters | MFI
PIC | Same |
| RET Performance Claims | | |
| Carryover | RET% Carryover 0.95
RET# r2>0.95 | | | |
| Reference
intervals | RET% (%):
Age 4-99 m/f: 0.5 – 2.5
Age 14-19 m/f: 0.5 – 2.0
Age 20-29 m/f: 0.6 – 2.0
Age 30-99 m/f: 0.6 – 2.5 | | | | | RET% (%):
Age > 18 f: 0.70 – 2.35
Age > 18 m: 0.70 – 2.06 | | | |
| | RET# (x106/mm3)
Age 4-13 m: 0.03 – 0.12
Age 4-13 f: 0.03 – 0.12
Age 14-19 m: 0.03 – 0.09
Age 14-19 f: 0.03 – 0.11
Age 20-29 m: 0.03 – 0.10
Age 20-29 f: 0.03 – 0.10
Age 30-99 m: 0.03 – 0.13
Age 30-99 f: 0.03 – 0.12 | | | | | RET# (x106/mm3)
Age > 18 f: 0.022 – 0.106
Age > 18 m: 0.024 – 0.106 | | | |
| | CRC (%):
Age 4-13 m: 0.50 – 1.64
Age 4-13 f: 0.58 – 2.38
Age 14-19 m: 0.52 – 1.74
Age 14-19 f: 0.57 – 2.22
Age 20-29 m: 0.70 – 2.07
Age 20-29 f: 0.56 – 1.97
Age 30-99 m: 0.70 – 2.66
Age 30-99 f: 0.55 – 2.50 | | | | | CRC (%):
Age > 18 f: 0.44 – 2.27
Age > 18 m: 0.51 – 2.15 | | | |
| | IRF: Not available | | | | | IRF:
Age > 18 f: 0.018 – 0.191
Age > 18 m: 0.033 – 0.232 | | | |
| Analytical
sensitivity | Not available | | | | | LoQ:
RET% (%): 0.7
RET# (x106/mm3): 0.01 | | | |
7.3 Comparison with predicate Device : Differences
12
SECTION 007 : 510(k) Summary
13
SECTION 007 : 510(k) Summary
| Item | ABX PENTRA DX 120 (K991839)
Predicate Device for RET
parameters | PENTRA XLR
Modified device |
|------------------|-----------------------------------------------------------------------|--------------------------------------------------|
| Sample stability | No claim when samples are stored at
room temperature | 24h at Room Temp. for RET%,
RET#, CRC and IRF |
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8.0 Special Control/Guidance Document Referenced :
8.1 Standards Followed
- CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement ● Methods - 2004
- CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedure: A ● Statistical Approach - 2003
- CLSI EP07-A2: Interference Testing in Clinical Chemistry - 2005
- CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples - 2013
- . CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures - 2012
- CLSI EP28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory - 2008
- CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers - 2010
- CLSI H44-A2: Methods for reticulocyte Counting (Automated Blood Cell Counters, ● Flow Cytometry, and Supravital Dyes); Approved Guideline - Second Edition - 2004
- IEC61010-1, IEC61010-2-081, IEC61010-2-101, UL61010-1, CAN/CSA-C22.2 No. ● 61010-1-12, CAN/CSA-C22.2 No. 61010.2.081-04, CAN/CSA-C22.2 No. 61010-2-101-04: Safety requirements for electrical equipment for measurement, control, and laboratory use
- EN61326-1, EN61326-2-6: Electrical equipment for measurement, control and laboratory use - EMC requirements
- . EN60825-1: Safety of Laser products - Part 1: Equipment classification and requirements
- ISO14971: Medical devices – Application of risk management to medical devices
8.2 FDA Guidances Followed
- Guidance for Industry and FDA Staff : Format for Traditional and Abbreviated 510(k)s -● 2005
- Final Guidance for Industry and FDA: Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells - 2001
- Guidance for Industry and FDA Staff : Guidance for the Content of Premarket ● Submissions for Software Contained in Medical Devices - 2005
- Guidance for Industry, FDA Reviewers and Compliance on Off-The-Shelf Software Use ● in Medical Devices - 1999
- Guidance for Industry and Food and Drug Administration Staff on the Content of Premarket Submissions for Management of Cybersecurity in Medical Devices - 2014
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9.0 Summary of Performance Data :
Note :
RET parameters included in this submission are the following:
- . RET#
- . RET%
- CRC
- IRF
RET# are calculated using RBC value.
The RBC value reported in the RET mode is obtained from a measurement identical to the existing RBC measurement on the ABX PENTRA 80.
The performance of the PENTRA XLR RBC parameter obtained in RET mode has been verified during the RET parameters validation. The RBC parameter performance is identical to the performance obtained in CBC mode and previously detailed to FDA through K024002.
9.1 Analytical Performance
9.1.1 Analytical Limits at Low Level
Limit of Blank (LoB) and Limit of Detection (LoD) studies cannot be performed for Reticulocyte parameters, because it is not possible to have result when there is no or not enough RBC in the sample. A verification of the LoB and LoD has been done for the RBC parameter.
Analytical sensitivity has been determined for the Reticulocyte parameters according to CLSI H44-A2 guideline. A verification of the LoQ according to CLSI EP17-A2 guideline has been done for the RBC parameter.
Limit of Blank (LoB)
Plasma samples, obtained by centrifugation of normal samples, were used as blank samples, in order to be as close as possible as the blood sample matrix.
To estimate the LoB, a total of 60 repeated measurements of different plasma are run in the same series (6 different samples run 10 times).
This test is performed on 2 PENTRA XLR instruments with two reagents lots.
RBC results on PENTRA XLR met specifications and are consistent with ABX PENTRA 80 claim.
LoB obtained from 60 repeated measurements of 6 different plasma samples, are:
| Measurand | LoB |
|---|---|
| RBC | 0 x 106/mm3 |
Limit of Detection (LoD)
A set of six samples with very low parameter concentration (i.e. in the range LoB and 4 x LoB) are run 10 times over several days.
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To estimate the LOD, take 60 results and calculate the pooled standard deviation (SDs). This test is performed on 2 PENTRA XLR instruments with two reagents lots. RBC results on PENTRA XLR met specifications and are consistent with ABX PENTRA 80 claim.
LoD obtained from 10 runs of 6 low samples on each instrument are:
| Measurand | LoD |
|---|---|
| RBC | $0.01 x 10^6/mm^3$ |
Analytical sensitivity - Limit of Quantitation (LoQ)
For Reticulocyte parameters: ●
To estimate the analytical senstivity for Reticulocyte parameters, a range of linearity in low concentrations is prepared. 7 levels are prepared and run 4 times each. This test is performed on at least 3 PENTRA XLR instruments with four reagents lots.
The Analytical sensitivity data are considered acceptable when the distribution of the residuals is randomly distributed and r2 higher than 0.98. The lowest value obtained in agreement with the acceptance criteria is the sensitivity limit and will be used as low limit for measuring range.
Analytical sensitivity limits obtained are:
| Measurand | Analytical sensitivity |
|---|---|
| RET% | 0.7% |
| RET# | 0.01 x 106/mm3 |
For RBC parameter: ●
To estimate the limit of quantitation, several ranges of linearity in low concentrations are prepared. Between 3 to 6 samples by level are prepared and run at least 5 times each, 40 replicates by level are necessary. The LoQ data are considered acceptable when the %Total-error is smaller than the desired total error for each measurand.
This test is performed on 2 PENTRA XLR instruments with two reagents lots.
RBC results on PENTRA XLR met specifications and are consistent with ABX PENTRA 80 claim.
LoQ obtained from at least 40 runs of 4 samples by level are:
| Measurand | LoQ |
|---|---|
| RBC | $0.24 \times 10^{6}/mm^{3}$ |
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9.1.2 Precision(Repeatability/Reproducibility) Imprecision (Repeatability)
Repeatability was performed using a minimum of 10 normal and 5 abnormal fresh whole blood samples collected into tubes containing K2EDTA anticoagulant, at 3 different clinical sites. Each sample was run 12 consecutive times on the PENTRA XLR, in a single day and all runs were completed within 8 hours of sample collection.
The size of the standard deviation (SD) was compared with the mean value of each parameter. This standard deviation divided by the mean is known as the Coefficient of Variation (CV) and is expressed as a percentage: CV% = (100*[Standard Deviation/Mean])
The results obtained were in the specifications. RBC results are consistent with ABX PENTRA 80 claim.
| Parameter | Low level | Normal Level | High Level | |||
|---|---|---|---|---|---|---|
| Claim | Level | Claim | Level | Claim | Level | |
| RET% (%) | Not applicable | CV% 3 | ||||
| RET# | ||||||
| (10 6/mm³) | Not applicable | CV% 0.1 | ||||
| CRC (%) | Not applicable | CV% 2.3 | ||||
| IRF | SD 0.30 | |||||
| RBC | ||||||
| (10 6/mm³) | CV% 6 |
Precision (Repeatability) Acceptance Criteria
Imprecision (Reproducibility)
Reproducibility was assessed on four PENTRA XLR instruments at four different sites, each with its own operator. On each site; High, Normal, and Low levels of one single lot of control material (Minotrol Retic for the Reticulocyte parameters Difftrol for the RBC parameter) were run in duplicate, twice each day, during a minimum of 25 days.
Total standard deviation and CV% were calculated for each measurand and results obtained were in the specifications. RBC results are consistent with ABX PENTRA 80 claim.
| Minotrol Retic | ||||||
|---|---|---|---|---|---|---|
| Parameter | Low Level Control | Normal Level Control | High Level Control | |||
| CV within-run | CV total | CV within-run | CV total | CV within-run | CV total | |
| RET% | 15% | 18% | 6% | 10% | 7% | 8% |
| RET# | 10% | 18% | 10% | 10% | 7% | 8% |
| CRC | 10% | 18% | 8% | 10% | 5% | 8% |
| IRF | 10% | 15% | 5% | 12% | 3% | 10% |
| RBC | 2% | 3% | 2% | 3% | 2% | 3% |
| Difftrol | ||||||
| Parameter | Low Level Control | Normal Level Control | High Level Control | |||
| CV within-run | CV total | CV within-run | CV total | CV within-run | CV total | |
| RBC | 2.0% | 3.0% | 1.5% | 2.5% | 1.2% | 2.5% |
Precision (Reproducibility) Acceptance Criteria
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Linearity / Assay's Measuring (Reportable) Range 9.1.3
Commercial Linearity kits were used to perform the linearity studies. The expected values of the kit samples were considered the "true values". Each level was run in replicates of four (n=4) as recommended by the kit supplier. For each level, the 4 replicate results wersus the theoretical value. The findings of the polynomial regression analysis indicate that the PENTRA XLR exhibits linearity across the claimed range.
The Analytical Measuring Range is defined as the range comprised between the Analytical Limit or Limit of Quantitation and the High Linearity Limit determined for each parameter. The claimed AMR are therefore:
| Parameter | AMR on PENTRA XLR |
|---|---|
| RET% (%) | 0.7 - 27 |
| RET# (106/mm3) | 0.01 - 0.5 |
| RBC (106/mm3) | 0.2 - 8.0 |
RBC results are consistent with ABX PENTRA 80 claim.
9.1.4 Carryover
The potential for sample carryover was tested in duplicate on the PENTRA XLR instrument using alternating high and low concentrations samples.
The percentage of carryover is calculated using the formula below:
$$Ct,% = \frac{low,,4-low,,6}{high,,3-low,,6} \times 100$$
All carry-over results are within specifications for the PENTRA XLR System. RBC results are consistent with ABX PENTRA 80 claim.
| | Carry-over Limit
(%CV) |
|------|---------------------------|
| RBC |