(576 days)
XN-10, XN-20
No
The summary describes a standard automated hematology analyzer and slide maker stainer. There is no mention of AI, ML, or any advanced algorithms beyond typical data processing for quantitative measurements and flagging. The performance studies focus on standard analytical validation metrics.
No
The device is an in-vitro diagnostic system that performs blood analysis to provide quantitative results for various measurands, rather than directly treating or impacting a patient's health.
Yes
The "Intended Use / Indications for Use" states that the device is "intended for screening patient populations found in clinical laboratories" and is "indicated to identify patients with hematologic parameters within and outside of established reference ranges." This demonstrates its role in diagnosing and monitoring patient conditions. It also explicitly states "For in-vitro diagnostic use."
No
The device description explicitly states it is a "multimodule system that consists of different combinations of one or more of the following modules: a quantitative multi-parameter automated hematology analyzer (Alinity hg) and an automated slide maker stainer (Alinity hs)." These are physical hardware components, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section explicitly states: "For in-vitro diagnostic use."
- Nature of the Device: The device is a hematology analyzer and slide maker stainer. These types of devices are used to analyze blood samples in vitro (outside the body) to provide diagnostic information about a patient's health.
- Measurands: The device measures various blood parameters (WBC, RBC, HGB, etc.) which are used by healthcare professionals to diagnose and monitor medical conditions.
- Intended Use: The intended use is for "screening patient populations found in clinical laboratories by qualified health care professionals," which is a typical application for IVD devices.
N/A
Intended Use / Indications for Use
The Alinity h-series System is an integrated hematology analyzer (Alinity hq) and slide maker stainer (Alinity hs) intended for screening patient populations found in clinical laboratories by qualified health care professionals. The Alinity h-series System can be configured as:
- · One standalone automated hematology analyzer system.
- A multimodule system that includes at least one Alinity hq analyzer module and may include one Alinity hs slide maker stainer module.
The Alinity hq analyzer module provides complete blood count and a 6-part white blood cell differential for normal and abnormal cells in capillary and venous whole blood collected in K2EDTA. The Alinity hq analyzer provides quantitative results for the following measurands: WBC, NEU, %N, MON, %M, EOS, %E, BASO, %B, 1G, %IG, RBC, HCT, HGB, MCV, MCH, MCHC, MCHr, RDW, NRBC, NR/W, RETIC, %R, IRF, PLT, MPV, %oP. The Alinity hq analyzer module is indicated to identify patients with hematologic parameters within and outside of established reference ranges. The Alinity hs slide maker stainer module automates whole blood film preparation and staining and stains externally prepared whole blood smears.
For in-vitro diagnostic use.
Product codes
GKZ, KPA
Device Description
The Alinity h-series system is a multimodule system that consists of different combinations of one or more of the following modules: a quantitative multi-parameter automated hematology analyzer (Alinity hg) and an automated slide maker stainer (Alinity hs).
The modules are designed to fit together. Each module has an internal conveyor that enables racks of specimen tubes to be transported between modules. The system can move racks between modules to perform different tests on a given specimen (e.g., make slide smears on the Alinity hs).
Principles of Operation
The Alinity hq uses flow cytometry and absorption spectrophotometry technologies to measure, count, and calculate hematological parameters in samples.
Two methods are used to introduce a specimen to the Alinity hq module:
- Closed-tube processing mode
- Open-tube processing mode
The Alinity hs module creates and stains smears from whole blood samples in addition to staining externally prepared smears for morphologic review. The operator selects and may configure staining protocols as needed by the laboratory. The Alinity hs module is configured with the May-Grünwald-Giemsa stain or the Wright-Giemsa stain.
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
pediatric (≤ 21 years) and adult (> 21 years)
Intended User / Care Setting
clinical laboratories by qualified health care professionals.
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
Method Comparison
A total of 2,194 unique venous and/or capillary specimens collected in K2EDTA tubes from pediatric (≤ 21 years) and adult (> 21 years) subjects including a wide variety of disease states (clinical conditions) were tested across 7 clinical sites. For each measurand, each specimen was tested within 8 hours from the time of collection in 1 replicate using either the Closed or Open tube processing mode in the CBC+Diff+Retic test selection on the Alinity h-series System and in 1 replicate on the Sysmex (XN-10, XN-20) System.
Sensitivity and Specificity
Sensitivity and specificity performance of the Alinity h-series System was assessed by identifying distributional abnormalities and morphological flags using blood films from venous and capillary specimens collected in K2EDTA tubes.
For this analysis, separate 2x2 tables were constructed in order to determine sensitivity for both morphological and distributional abnormalities.
Precision (Repeatability)
Samples from 32 unique donors (16 normal and 16 pathological around medical decision points) were collected in K2EDTA tubes and tested in a minimum of 32 consecutive replicates for normal samples and a minimum of 10 consecutive replicates for pathological samples.
System Reproducibility
The reproducibility study was performed at three clinical sites using a single lot of Alinity h-series 29P Control (low, normal, high). Each control level was tested for 5 days with 3 runs per day and in a minimum of 2 replicates per run.
Linearity
Linearity for RBC, HGB, and NRBC was determined using whole blood to span the analytical measuring interval of each measurand. Linearity for WBC, PLT, and RETIC was determined using commercially available linearity kits. For each measurand, the testing minimally included:
- 9 levels
- 4 replicates of each level
- 1 instrument
- 1 set of reagent lots
Carryover
Venous whole blood specimens were collected in K2EDTA tubes. For each measurand, a minimum of 4 carryover runs was completed at each of 4 testing sites for a minimum of 16 total carryover runs per measurand, where each run consisted of testing a high target specimen in 3 replicates followed by testing a low target specimen in 3 replicates.
Potentially Interfering Substances Study
The susceptibility of the Alinity h-series System to interference in the presence of hemoglobin, triglycerides, bilirubin, cholesterol, elevated WBCs, elevated RBCs, elevated PLTs, and microcytic RBCs was tested in samples collected in K2EDTA tubes.
Limits of Blank, Detection, and Quantitation (LoB, LoD, and LoO)
Testing was conducted over a minimum of 3 days using a minimum of 2 unique samples per day on each of 2 test selections (CBC+Diff and CBC+Diff+Retic) in a minimum of 5 replicates using each of the 2 sets of reagent lots.
Specimen Stability
For venous specimen stability, a minimum of 10 abnormal and 10 normal venous whole blood specimens K2EDTA and K3EDTA tubes. Each specimen was tested in a minimum of 2 replicates. For capillary specimen stability, a minimum of 20 normal whole blood specimens were collected in K2EDTA and K3EDTA tubes. Each specimen was tested in a minimum of 1 replicate. All samples were tested within 4 hours (baseline) of specimen collection. Samples stored at Refrigerated Temperature (2-8℃) were tested at up to 24 hours after specimen collection. Samples stored at Room Temperature (18-26℃) were tested at up to 48 hours after specimen collection.
Anticoagulant Comparability (K3EDTA versus K2EDTA)
A total of 199 unique adult and pediatric donor sets covering relevant medical decision levels and reference ranges and spanning the analytical measurement ranges to the extent possible were tested in 2 replicates for each measurand.
Microtainer Capillary versus Microtube for Automated Process (MAP)
A total of 44 unique donor sets (normal whole blood specimens) were collected in K2EDTA Microtainer Capillary and Microtainer Microtube for Automated Process (MAP) blood collection tubes. Each specimen was tested in 1 replicate in the open-tube processing mode for each measurand.
Matrix Comparability (Capillary versus Venous)
A total of 76 unique venous and capillary donor sets (normal and abnormal whole blood specimens) were collected in Microtainer Microtube for Automated Process (MAP) Microtubes (capillary specimens) and standard K2EDTA tubes (venous specimens). Each specimen was tested in 2 replicates for each measurand.
Sample/Tube Processing Mode Comparability (Open Mode versus Closed Mode)
A total of 226 unique venous specimens covering relevant medical decision levels and reference ranges and spanning the analytical measurement ranges to the extent possible were collected in K2EDTA tubes. Each specimen was tested in 2 replicates in the closed-tube and open-tube processing modes for each measurand.
Reference Intervals (Expected Values)
A total of 261 unique venous and 1 capillary whole blood specimens collected from 126 male and 136 female adult subjects were tested in a minimum of 1 replicate to establish adult reference intervals. A total of 360 venous or capillary specimens from pediatric sub-populations: 61 neonates (birth to 1 month); 68 infant (> 1 month to 2 years old), 109 child (> 2 to 12 years old), and 122 adolescents (> 12 to 21 years old) were tested in 1 replicate to establish pediatric reference intervals for each measurand.
Summary of Performance Studies
1. Method Comparison
Study Type: Comparison to predicate device
Sample Size: 2,194 unique venous and/or capillary specimens
Key Results: Passing-Bablok and Deming regression analyses were performed. All results were within the predefined acceptance criteria and found to be acceptable. Biases at critical points were evaluated and found acceptable.
2. Sensitivity and Specificity
Study Type: Diagnostic accuracy
Sample Size: 674 specimens (from table)
Key Results: Sensitivity: 80.19% (75.38%, 84.43%), Specificity: 76.40% (71.64%, 80.72%), Efficiency: 78.19% (74.88%, 81.25%). All results were within the predefined acceptance criteria and found to be acceptable.
3. Precision (Repeatability)
Study Type: Repeatability
Sample Size: 32 unique donors (16 normal, 16 pathological)
Key Results: Mean, standard deviation (SD), coefficient of variation (CV), and 95% CI were calculated for each parameter. All results met the predefined acceptance criteria and were determined to be acceptable.
4. System Reproducibility
Study Type: Reproducibility
Sample Size: Samples from a single lot of Alinity h-series 29P Control (low, normal, high) tested for 5 days with 3 runs/day, 2 replicates/run at 3 sites.
Key Results: Within-laboratory %CV or SD for each control level were calculated and presented in tables. All results met the predefined acceptance criteria and were determined to be acceptable.
5. Linearity
Study Type: Linearity
Sample Size: Not explicitly stated as overall sample size; minimum 9 levels, 4 replicates each per measurand.
Key Results: A weighted linear regression analysis was used. All results met the predefined acceptance criteria and were determined to be acceptable across the specified linear ranges.
6. Carryover
Study Type: Carryover assessment
Sample Size: Minimum of 4 carryover runs at each of 4 testing sites (minimum 16 total runs per measurand).
Key Results: All results met the predefined acceptance criteria and were determined to be acceptable.
7. Potentially Interfering Substances Study
Study Type: Interference
Sample Size: Not explicitly stated.
Key Results: The device's susceptibility to interference from hemoglobin, triglycerides, bilirubin, cholesterol, elevated WBCs, elevated RBCs, elevated PLTs, and microcytic RBCs was tested. All results met the predefined acceptance criteria and were determined to be acceptable.
8. Limits of Blank, Detection, and Quantitation (LoB, LoD, and LoQ)
Study Type: Analytical sensitivity (LoB, LoD, LoQ determination)
Sample Size: Testing conducted over a minimum of 3 days using a minimum of 2 unique samples per day on each of 2 test selections in a minimum of 5 replicates each.
Key Results: Maximum observed LoB, LoD, and LoQ values are summarized. All results met the predefined acceptance criteria and were determined to be acceptable.
9. Specimen Stability
Study Type: Specimen stability
Sample Size: Minimum 10 abnormal/10 normal venous specimens, minimum 20 normal capillary specimens.
Key Results: Results were used to support information in the system labeling for venous and capillary specimen stability.
10. Anticoagulant Comparability (K3EDTA versus K2EDTA)
Study Type: Comparability
Sample Size: 199 unique adult and pediatric donor sets.
Key Results: Comparability was assessed based on mean difference or % difference and regression analysis. All reportable parameters met predefined bias acceptance criteria.
11. Microtainer Capillary versus Microtube for Automated Process (MAP)
Study Type: Comparability
Sample Size: 44 unique donor sets.
Key Results: Comparability assessed based on mean difference or % difference and regression analysis. All reportable parameters met predefined bias acceptance criteria.
12. Matrix Comparability (Capillary versus Venous)
Study Type: Matrix comparability
Sample Size: 76 unique venous and capillary donor sets.
Key Results: Comparability assessed based on mean difference or % difference and regression analysis. All reportable parameters met predefined bias acceptance criteria.
13. Sample/Tube Processing Mode Comparability (Open Mode versus Closed Mode)
Study Type: Processing mode comparability
Sample Size: 226 unique venous specimens.
Key Results: Comparability assessed based on mean difference or % difference and regression analysis. All reportable parameters met predefined bias acceptance criteria.
14. Reference Intervals (Expected Values)
Study Type: Reference interval establishment
Sample Size: 261 unique venous and 1 capillary specimens from adults; 360 venous or capillary specimens from pediatric sub-populations.
Key Results: Reference intervals were established for adult male/female and pediatric subgroups.
Key Metrics
Sensitivity and Specificity:
Sensitivity: 80.19% (95% CI: 75.38%, 84.43%)
Specificity: 76.40% (95% CI: 71.64%, 80.72%)
Efficiency: 78.19% (95% CI: 74.88%, 81.25%)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
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/0 description: The image contains the logo of the U.S. Food & 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.
August 4, 2023
Abbott Laboratories Neha Vatsyayan Regulatory Affairs Project Manager 4551 Great America Pkwy Santa Clara, California 95054
Re: K220031
Trade/Device Name: Alinity h-series System Regulation Number: 21 CFR 864.5220 Regulation Name: Automated Differential Cell Counter Regulatory Class: Class II Product Code: GKZ Dated: March 29, 2023 Received: March 31, 2023
Dear Neha Vatsyayan:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
1
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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Min V
Min Wu, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K220031
Device Name Alinity h-series System
Indications for Use (Describe)
The Alinity h-series System is an integrated hematology analyzer (Alinity hq) and slide maker stainer (Alinity hs) intended for screening patient populations found in clinical laboratories by qualified health care professionals. The Alinity h-series System can be configured as:
- · One standalone automated hematology analyzer system.
· A multimodule system that includes at least one Alinity hq analyzer module and may include one Alinity hs slide maker stainer module.
The Alinity hq analyzer module provides complete blood count and a 6-part white blood cell differential for normal and abnormal cells in capillary and venous whole blood collected in K2EDTA. The Alinity hq analyzer provides quantitative results for the following measurands: WBC, NEU, %N, MON, %M, EOS, %E, BASO, %B, 1G, %IG, RBC, HCT, HGB, MCV, MCH, MCHC, MCHr, RDW, NRBC, NR/W, RETIC, %R, IRF, PLT, MPV, %oP. The Alinity hq analyzer module is indicated to identify patients with hematologic parameters within and outside of established reference ranges. The Alinity hs slide maker stainer module automates whole blood film preparation and staining and stains externally prepared whole blood smears.
For in-vitro diagnostic use.
| 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) | ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the
time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
3
Section 5: 510(k) Summary
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
I. Applicant Name
Abbott Laboratories 4551 Great America Pkwy, Santa Clara, CA 95054 Date Prepared: April 28, 2023
Contact: Neha Vatsyayan Regulatory Affairs Project Manager Abbott Diagnostics Division Phone: (408) 313 4401 E-Mail: neha.vatsyayan@abbott.com
II. Device Information
Trade name (proprietary name): Alinity h-series system Common name (usual name): Automated Hematology Analyzer and Slide Maker Stainer Classification Name: Automated Differential Cell Counter
III. Regulatory Information
Alinity hq (Analyzer) Device Classification: Class II Regulation Description: Automated Differential Cell Counter Governing Regulation: 21 CFR 864.5220 Code: GKZ Alinity hs (Slide maker stainer) Device Classification: Class I Regulation Description: Automated Slide Stainer Governing Regulation: 21 CFR 864.3800 Code: KPA
4
IV. Predicate Device
Sysmex® XN-Series (XN-10, XN-20) Automated Hematology Analyzers (K112605)
V. Device Description
The Alinity h-series system is a multimodule system that consists of different combinations of one or more of the following modules: a quantitative multi-parameter automated hematology analyzer (Alinity hg) and an automated slide maker stainer (Alinity hs).
The modules are designed to fit together. Each module has an internal conveyor that enables racks of specimen tubes to be transported between modules. The system can move racks between modules to perform different tests on a given specimen (e.g., make slide smears on the Alinity hs).
Principles of Operation
The Alinity hq uses flow cytometry and absorption spectrophotometry technologies to measure, count, and calculate hematological parameters in samples.
Two methods are used to introduce a specimen to the Alinity hq module:
- . Closed-tube processing mode
- . Open-tube processing mode
The Alinity hs module creates and stains smears from whole blood samples in addition to staining externally prepared smears for morphologic review. The operator selects and may configure staining protocols as needed by the laboratory. The Alinity hs module is configured with the May-Grünwald-Giemsa stain or the Wright-Giemsa stain.
Intended Use
The Alinity h-series system is an integrated hematology analyzer (Alinity hq) and slide maker stainer (Alinity hs) intended for screening patient populations found in clinical laboratories by qualified health care professionals. The Alinity h-series can be configured as:
- One standalone automated hematology analyzer system. •
- A multimodule system that includes at least one Alinity hq analyzer module and may . include one Alinity hs slide maker stainer module.
5
The Alinity hq analyzer module provides complete blood count and a 6-part white blood cell differential for normal and abnormal cells in capillary and venous whole blood collected in K2EDTA or K3EDTA. The Alinity hq analyzer provides quantitative results for the following measurands: WBC, NEU, %N, LYM, %L, MONO, %M, EOS, %E, BASO, %B, IG, %IG, RBC, HCT, HGB, MCV, MCH, MCHC, MCHr, RDW, NRBC, NR/W, RETIC, %R, IRF, PLT, MPV, %rP. The Alinity hq analyzer module is indicated to identify patients with hematologic parameters within and outside of established reference ranges. The Alinity hs slide maker stainer module automates whole blood film preparation and staining and stains externally prepared whole blood smears.
For in-vitro diagnostic use.
Definitions of Reportable Parameters
Definitions of the reportable parameters are presented in Table 5-1.
6
| Abbreviation | Definition |
|---|---|
| White Blood Cell Parameters | |
| BASO | Basophil absolute concentration |
| %B | Basophil percentage of WBCs (%BASO) |
| EOS | Eosinophil absolute concentration |
| %E | Eosinophil percentage of WBCs (%EOS) |
| IG | Immature Granulocyte concentration |
| %IG | Immature Granulocyte percentage |
| LYM | Lymphocyte absolute concentration |
| %L | Lymphocyte percentage of WBCs (%LYM) |
| MONO | Monocyte absolute concentration |
| %M | Monocyte percentage of WBCs (%MON) |
| NEU | Neutrophil absolute concentration |
| %N | Neutrophil percentage of WBCs (%NEU) |
| WBC | White Blood Cell concentration |
| Table 5-1 |
|---|
| Peripheral Whole Blood Reportable Parameters |
| Abbreviation | Definition |
|---|---|
| Red Blood Cell Parameters | |
| HCT | Hematocrit |
| HGB | Hemoglobin concentration |
| IRF | Immature Reticulocyte Fraction |
| MCH | Mean Cell Hemoglobin |
| MCHC | Mean Cell Hemoglobin Concentration |
| MCHr | Mean cell hemoglobin of the reticulocyte |
| MCV | Mean Cell Volume |
| NRBC | Nucleated red blood cell absolute concentration |
| NR/W | NRBCs per 100 WBCs |
| RETIC | reticulocyte concentration (RETC) |
| RBC | Red Blood Cell concentration |
| RDW | red blood cell distribution width |
| %R | Reticulocyte percentage of RBCs (%RETC) |
| Platelet Parameters | |
|---|---|
| PLT | Platelet concentration |
| MPV | Mean Platelet Volume |
| %rP | Reticulated Platelet percentage |
7
VI. Comparison of Technological Characteristics
The similarities and differences between the subject device and the predicate device are
presented in the Device Similarities and Differences tables below.
| Device Similarities | ||
|---|---|---|
| Subject Device: | Predicate Device: | |
| Item | Alinity h-series System | Sysmex® XN-Series (XN-10, XN-20) |
| Intended | ||
| Use | The Alinity h-series system is an integrated | |
| hematology analyzer (Alinity hq) and slide | ||
| maker stainer (Alinity hs) intended for | ||
| screening patient populations found in | ||
| clinical laboratories by qualified health care | ||
| professionals. The Alinity h-series can be | ||
| configured as: | ||
| • One standalone automated hematology | ||
| analyzer system. | ||
| • A multimodule system that includes at | ||
| least one Alinity hq analyzer module and | ||
| may include one Alinity hs slide maker | ||
| stainer module. | ||
| The Alinity hq analyzer module provides | ||
| complete blood count and a 6-part white | ||
| blood cell differential for normal and | ||
| abnormal cells in capillary and venous | ||
| whole blood collected in K2EDTA or | ||
| K3EDTA. The Alinity hq analyzer provides | ||
| quantitative results for the following | ||
| measurands: WBC, NEU, %N, LYM, %L, | ||
| ΜΟΝΟ, %M, EOS, %E, BASO, %B, | ||
| IG, %IG, RBC, HCT, HGB, MCV, MCH, | ||
| MCHC, MCHr, RDW, NRBC, NR/W, | ||
| RETIC, %R, IRF, PLT, MPV, %rP. The | ||
| Alinity hq analyzer module is indicated to | ||
| identify patients with hematologic | ||
| parameters within and outside of established | ||
| reference ranges. The Alinity hs slide maker | ||
| stainer module automates whole blood film | ||
| preparation and staining and stains | ||
| externally prepared whole blood smears. | ||
| For in-vitro diagnostic use. | The Sysmex XN-10 and XN-20 modules | |
| 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 for | ||
| whole blood: | ||
| WBC, RBC, HGB, HCT, MCV, MCH, | ||
| MCHC, PLT, NEUT%/#, LYMPH%/#, | ||
| ΜΟΝΟ%/#, EO%/#, BASO%/#, | ||
| NRBC%/#, IG%/#, RDW-CV, RDW-SD, | ||
| MPV, RET%/#, IRF, IPF, RET-He and has | ||
| a Body Fluid mode for body fluids. The | ||
| Body Fluid mode enumerates the WBC-BF, | ||
| RBC-BF, MN%/#, PMN%/# and TC-BF# | ||
| parameters in cerebrospinal fluids (CSF), | ||
| serous fluids (peritoneal, pleural) and | ||
| synovial fluids. Whole blood should be | ||
| collected in K2 or K3EDTA anticoagulant | ||
| and serous and synovial fluids in K2EDTA | ||
| anticoagulant to prevent clotting of fluid. | ||
| The use of anticoagulants with CSF | ||
| specimens is neither required nor | ||
| recommended. |
Table 5-2 Device Similarities and Differences
8
| Device Similarities (Continued) | |||
|---|---|---|---|
| Item | Subject Device: | ||
| Alinity h-series System | Predicate Device: | ||
| Sysmex® XN-Series | |||
| (XN-10, XN-20) | |||
| Test Principle | Performs hematology analyses | ||
| according to flow cytometry | |||
| method (using Hydro Dynamic | |||
| Focusing) and absorption | |||
| spectrophotometry method (using | |||
| cyan-methemoglobin). | Performs hematology analyses | ||
| according to flow cytometry | |||
| method (using Hydro Dynamic | |||
| Focusing), and absorption | |||
| spectrophotometry method (using | |||
| sodium lauryl sulphate (SLS)) | |||
| Parameters 1 | Whole Blood Mode: | ||
| WBC, RBC, HGB, HCT, MCV, | |||
| MCH, MCHC, PLT, | |||
| MPV, IRF, | |||
| NEU, %N, | |||
| LYM, %L, | |||
| MONO, %M, | |||
| EOS, %E, | |||
| BASO, %B, | |||
| NRBC, NR/W, | |||
| IG, %IG, | |||
| RETIC, %R, | |||
| RDW, | |||
| MCHr, | |||
| %rP | Whole Blood Mode: | ||
| WBC, RBC, HGB, HCT, MCV, | |||
| MCH, MCHC, PLT, | |||
| MPV, IRF, | |||
| NEUT%/#, | |||
| LYMPH%/#, | |||
| MONO%/#, | |||
| EO%/#, | |||
| BASO%/#, | |||
| NRBC%/#, | |||
| IG%/#, | |||
| RET%/#, | |||
| RDW-CV, RDW-SD, | |||
| RET-He#, | |||
| IPF | |||
| Specimen Type | Whole blood | Whole blood | |
| Use of Controls/ | |||
| Calibrators | Yes | Yes | |
| IPU | Multi-Module connect | Multi-Module connect | |
| Sample Aspiration/ | |||
| Fluidic Pathway | Single aspiration pathway | Single aspiration pathway | |
| Software/Hardware | Rules based rerun / reflex | Rules-based rerun / reflex | |
| Device Differences | |||
| Item | Subject Device: | ||
| Alinity h-series System | Predicate Device: | ||
| Sysmex® XN-Series | |||
| (XN-10, XN-20) | |||
| Test Principle | The Alinity h-series System uses | ||
| flow cytometry method with Hydro | |||
| Dynamic Focusing to analyze whole | |||
| blood samples including RBC and PLT. | Sysmex XN-Series uses Hydro | ||
| Dynamic Focusing (Direct Current | |||
| Detection) for RBC and PLT. | |||
| Parameters | Not Applicable - Body Fluid test | ||
| selection is not included in this | |||
| submission. | Body Fluid Mode: | ||
| WBC-BF, RBC-BF, MN%/#, | |||
| PMN%/#, TC-BF# | |||
| Specimen Type | Not Applicable - Body Fluid is not | ||
| included in this submission. | Body Fluids [i.e., cerebrospinal | ||
| fluids (CSF), serous fluids | |||
| (peritoneal, pleural) and synovial | |||
| fluids] | |||
| Reagents | • Diluent | ||
| • HGB Reagent | |||
| • WBC Reagent | |||
| • Retic Reagent | CELLPACKTM DCL (Diluent) | ||
| CELLPACKTM 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) | |||
| Controls/ | |||
| Calibrators | Whole Blood: | ||
| • Calibrator - Alinity h-series HemCal | |||
| • Control - Alinity h-series Control 29P | |||
| No Body Fluids Mode on Alinity hq. | Whole Blood: | ||
| • XN-Check - 3 Levels | |||
| • XN CAL (XN-10/X-20 | |||
| Calibrator) | |||
| • XN CAL PF (Platelet F | |||
| Calibrator) | |||
| Body Fluid: | |||
| • XN Check BF – 2 Levels | |||
| Measuring | |||
| Channels/ | |||
| Methods | |||
| Selection | • CBC+Diff (for RBC, WBC, and PLT) | ||
| • CBC+Diff+Retic (for RBC, WBC, | |||
| PLT and Retic) | • RET/PLT | ||
| • WNR, WDF, WNR, WPC (Not | |||
| available in XN-10) | |||
| • PLT-F | |||
| Device Differences (Continued) | |||
| Item | Subject Device: | ||
| Alinity h-series System | Predicate Device: | ||
| Sysmex® XN-Series | |||
| (XN-10, XN-20) | |||
| Modules Connected to | |||
| the Analyzer | Required | ||
| Water Purification System | |||
| System Control Center Computer (SCC) | |||
| Optional | |||
| Laboratory Automation System (LAS) for | |||
| automatic sample loading | IPU (Information | ||
| processing unit) | |||
| Pneumatic Unit | |||
| Data Transfer Mode | USB, Internet, and Intranet | USB, CD-R, Internet, | |
| and Intranet |
Table 5-2, Continued Device Similarities and Differences
1 Different names/formats of equivalent parameters are used between the Alinity h-series System and Sysmex® XN-series; therefore, equivalent parameters are listed in the same row.
9
Table 5-2, Continued Device Similarities and Differences
10
Table 5-2, Continued Device Similarities and Differences
11
VII. Performance Characteristics:
A. Analytical Performance:
1. Method Comparison
The method comparison study was conducted based on guidance from the Clinical and Laboratory Standards Institute CLSI EP09c, 3rd edition2 to assess the performance of the Alinity hq when compared to the predicate device, Sysmex (XN-10, XN-20) (K112605). A total of 2,194 unique venous and/or capillary specimens collected in K2EDTA tubes from pediatric (≤ 21 years) and adult (> 21 years) subjects including a wide variety of disease states (clinical conditions) were tested across 7 clinical sites. For each measurand, each specimen was tested within 8 hours from the time of collection in 1 replicate using either the Closed or Open tube processing mode in the CBC+Diff+Retic test selection on the Alinity h-series System and in 1 replicate on the Sysmex (XN-10, XN-20) System.
Passing-Bablok and Deming regression analyses were performed with the investigational method as the dependent variable (y) and the predicate method as the independent variable (x).
Bias at the critical points (the upper and lower limits of the reference ranges and relevant medical decision levels) were also evaluated for each site individually and for all sites combined. All results were within the predefined acceptance criteria and found to be acceptable. The method comparison results are shown in the table below.
² Clinical and Laboratory Standards Institute (CLSI). Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Third Edition. CLSI Document EP09-A3. Wayne, PA: CLSI; 2013.
12
| Measurand | N | Sample Range | r
(95% CI) | Slope
(95% CI) | Intercept
(95% CI) | | Critical Points | Bias | | %Bias | |
|------------------|------|----------------|----------------------|----------------------|-------------------------|----------------|-----------------|----------|--------------|----------|--------------|
| WBC (X 103/μL) | 2002 | 0.07 - 436.00 | 1.00
(1.00, 1.00) | 1.00
(1.00, 1.00) | 0.01
(0.00, 0.03) | Measurand | | Estimate | 95% CI | Estimate | 95% CI |
| %N (%) | 1551 | 7.56 - 98.30 | 0.99
(0.99, 1.00) | 1.00
(1.00, 1.01) | 0.22
(-0.10, 0.50) | HGB (g/dL) | 8.00 | 0.17 | 0.16, 0.20 | 2.18 | 2.03, 2.48 |
| %L (%) | 1640 | 0.34 - 84.60 | 1.00
(1.00, 1.00) | 1.00
(0.99, 1.00) | 0.08
(0.00, 0.16) | | 12.0 | 0.14 | 0.13, 0.17 | 1.17 | 1.09, 1.43 |
| %M (%) | 1646 | 0.03 - 49.20 | 0.98
(0.97, 0.98) | 0.99
(0.98, 1.00) | -0.03
(-0.13, 0.06) | | 16.2 | 0.11 | 0.09, 0.15 | 0.65 | 0.53, 0.90 |
| %E (%) | 1712 | 0.00 - 37.50 | 0.99
(0.99, 0.99) | 1.02
(1.01, 1.03) | 0.02
(0.01, 0.03) | HCT (%) | 14.0 | -0.25 | -0.37, -0.11 | -1.75 | -2.61, -0.81 |
| %B (%) | 1854 | 0.00 - 8.37 | 0.45
(0.41, 0.49) | 1.53
(1.47, 1.59) | -0.14
(-0.17, -0.11) | | 35.4 | 0.13 | 0.06, 0.20 | 0.38 | 0.18, 0.57 |
| %IG (%)a | 1545 | 0.00 - 12.50 | 0.59
(0.56, 0.62) | 0.59
(0.45, 0.73) | -0.30
(-0.44, -0.15) | | 46.4 | 0.33 | 0.22, 0.45 | 0.71 | 0.46, 0.97 |
| NR/Wa | 1949 | 0.00 - 228.00 | 0.99
(0.99, 0.99) | 0.97
(0.93, 1.02) | -0.07
(-0.13, -0.01) | | 70.0 | 0.75 | 0.51, 1.00 | 1.07 | 0.72, 1.42 |
| RBC (X 106/μL) | 1993 | 0.60 - 8.03 | 1.00
(0.99, 1.00) | 0.99
(0.99, 0.99) | 0.04
(0.03, 0.06) | MCV (fL) | 80.0 | -0.47 | -0.70, -0.29 | -0.58 | -0.88, -0.36 |
| HGB (g/dL) | 2006 | 1.64 - 23.30 | 1.00
(1.00, 1.00) | 0.99
(0.99, 0.99) | 0.24
(0.21, 0.28) | | 100 | 0.55 | 0.31, 0.82 | 0.55 | 0.31, 0.82 |
| HCT (%) | 1999 | 4.92 - 86.00 | 0.99
(0.99, 0.99) | 1.02
(1.01, 1.02) | -0.49
(-0.68, -0.29) | RDW (%) | 11.6 | 0.57 | 0.54, 0.63 | 4.93 | 4.64, 5.42 |
| MCV (fL) | 2001 | 51.40 - 131.00 | 0.95
(0.94, 0.95) | 1.05
(1.03, 1.07) | -4.56
(-6.06, -3.12) | | 14.0 | 0.23 | 0.20, 0.27 | 1.63 | 1.46, 1.93 |
| MCH (pg) | 1993 | 15.30 - 47.00 | 0.98
(0.97, 0.98) | 0.97
(0.96, 0.98) | 1.25
(0.94, 1.52) | WBC (X 103/μL) | 1.00 | 0.01 | 0.00, 0.02 | 1.09 | 0.03, 2.40 |
| MCHC (g/dL) | 1993 | 25.00 - 39.30 | 0.66
(0.63, 0.68) | 0.97
(0.92, 1.00) | 1.51
(0.40, 2.90) | | 3.54 | 0.01 | 0.00, 0.02 | 0.29 | 0.02, 0.54 |
| %R (%) | 1942 | 0.12 - 20.80 | 0.97
(0.96, 0.97) | 1.06
(1.04, 1.07) | 0.01
(-0.01, 0.03) | | 9.06 | 0.01 | -0.01, 0.02 | 0.10 | -0.10, 0.21 |
| IRF | 1935 | 0.00 - 0.70 | 0.89
(0.88, 0.90) | 0.94
(0.92, 0.96) | -0.01
(-0.01, -0.01) | | 30.0 | 0.00 | -0.08, 0.04 | 0.01 | -0.26, 0.13 |
| PLT (X 103/μL) | 1933 | 1.21 - 5144.00 | 0.99
(0.99, 0.99) | 0.97
(0.97, 0.98) | 0.27
(-0.41, 1.08) | %N (%) | 40.0 | 0.39 | 0.25, 0.60 | 0.99 | 0.62, 1.50 |
| Measurand | N | Sample Range | r
(95% CI) | Slope
(95% CI) | Intercept
(95% CI) | | 70.0 | 0.52 | 0.40, 0.60 | 0.74 | 0.57, 0.86 |
| MPV (fL) | 1723 | 8.04 - 13.30 | 0.73
(0.71, 0.75) | 0.94
(0.91, 0.99) | 0.29
(-0.14, 0.65) | %L (%) | 20.0 | 0.02 | -0.03, 0.10 | 0.09 | -0.14, 0.50 |
| %rP (%)b | 1910 | 0.55 - 42.10 | 0.82
(0.81, 0.84) | 0.78
(0.76, 0.80) | 0.62
(0.55, 0.69) | | 50.0 | -0.08 | -0.23, 0.10 | -0.15 | -0.46, 0.20 |
| MCHr (pg) | 1933 | 6.89 - 45.80 | 0.84
(0.82, 0.85) | 1.09
(1.06, 1.12) | -1.28
(-2.27, -0.29) | %M (%) | 4.00 | -0.05 | -0.11, -0.01 | -1.34 | -2.79, -0.25 |
| NEU (X 103/μL) | 1551 | 0.10 - 55.00 | 1.00
(1.00, 1.00) | 1.01
(1.01, 1.01) | 0.00
(-0.02, 0.02) | | 8.00 | -0.08 | -0.12, -0.05 | -1.00 | -1.53, -0.68 |
| LYM (X 103/μL) | 1640 | 0.05 - 27.20 | 0.99
(0.99, 1.00) | 0.99
(0.99, 1.00) | 0.02
(0.01, 0.03) | %E (%) | 0.00 | 0.02 | 0.01, 0.03 | NA | NA |
| MONO (X 103/μL) | 1646 | 0.00 - 8.84 | 0.99
(0.99, 0.99) | 1.02
(1.01, 1.03) | -0.02
(-0.03, -0.01) | | 6.00 | 0.16 | 0.11, 0.21 | 2.67 | 1.81, 3.42 |
| EOS (X 103/μL) | 1712 | 0.00 - 4.19 | 0.99
(0.99, 0.99) | 1.02
(1.01, 1.03) | 0.00
(0.00, 0.00) | %B (%) | 0.00 | -0.14 | -0.18, -0.11 | NA | NA |
| BASO (X 103/μL) | 1854 | 0.00 - 8.11 | 0.22
(0.18, 0.26) | 1.31
(1.27, 1.37) | 0.00
(-0.01, 0.00) | | 2.00 | 0.91 | 0.80, 1.01 | 45.57 | 40.05, 50.73 |
| IG (X 103/µL)ª | 1545 | 0.00 - 3.15 | 0.81
(0.80, 0.83) | 1.01
(0.85, 1.18) | -0.07
(-0.09, -0.05) | NEU (X 103/μL) | 0.50 | 0.01 | -0.01, 0.02 | 1.17 | -1.99, 4.10 |
| NRBC (X 103/μL)ª | 1945 | 0.00 - 17.70 | 0.91
(0.90, 0.92) | 0.88
(0.70, 1.07) | 0.01
(0.00, 0.02) | | 1.42 | 0.01 | 0.00, 0.03 | 0.97 | 0.03, 1.85 |
| RDW (%) | 2003 | 10.10 - 32.30 | 0.94
(0.93, 0.94) | 0.86
(0.84, 0.87) | 2.23
(2.06, 2.45) | | 6.34 | 0.06 | 0.04, 0.07 | 0.89 | 0.66, 1.12 |
| RETIC (X 103/uL) | 1935 | 1.96 - 614.00 | 0.96
(0.96, 0.97) | 1.05
(1.04, 1.06) | 0.79
(0.02, 1.64) | LYM (X 103/μL) | 25.0 | 0.22 | 0.13, 0.30 | 0.88 | 0.53, 1.19 |
| 1.00 | 0.01 | 0.00, 0.01 | 0.77 | 0.27, 1.28 | | | | | | | |
| | 4.00 | 0.02 | 0.04, 0.00 | 0.47 | 0.89, 0.95 | | | | | | |
All Sites Combined - Regression Analysis
4 A summary of the Deming regression model is presented for NRBC, NR/W, IG, and %IG. A summary of the Passing-Bablok regression model is presented for all other measurands.
13
All Sites Combined - Regression Analysis (Continued)
4 A summary of the Deming regression model is presented for NRBC, NR/W, IG, and %IG. A summary of the Passing-Bablok regression model is presented for all other measurands.
b %rP (%) on Alinity h-series System is equivalent to the Sysmex XN-10 IPF measurand.
14
All Sites Combined - Estimated Bias at Critical Points
NA = Not applicable since the critical point is zero.
15
| Measurand | Critical Points | Bias | %Bias | ||
|---|---|---|---|---|---|
| Estimate | 95% CI | Estimate | 95% CI | ||
| MONO (X 103/μL) | 0.20 | -0.01 | -0.02, -0.01 | -7.49 | -10.18, -5.56 |
| MONO (X 103/μL) | 1.00 | 0.00 | 0.00, 0.01 | 0.39 | -0.24, 0.95 |
| EOS (X 103/μL) | 0.00 | 0.0 | 0.00, 0.00 | NA | NA |
| EOS (X 103/μL) | 0.40 | 0.01 | 0.01, 0.01 | 2.72 | 1.96, 3.50 |
| EOS (X 103/μL) | 1.50 | 0.04 | 0.02, 0.05 | 2.38 | 1.56, 3.21 |
| BASO (X 103/μL) | 0.00 | 0.00 | -0.01, 0.00 | NA | NA |
| BASO (X 103/μL) | 0.20 | 0.06 | 0.05, 0.07 | 29.22 | 24.67, 34.63 |
| BASO (X 103/μL) | 1.00 | 0.31 | 0.26, 0.37 | 30.73 | 25.66, 36.94 |
| %IG (%) | 0.00 | -0.30 | -0.44, -0.15 | NA | NA |
| %IG (%) | 1.00 | -0.71 | -0.74, -0.68 | -70.96 | -73.67, -68.25 |
| %IG (%) | 2.00 | -1.12 | -1.26, -0.99 | -56.13 | -62.86, -49.39 |
| NR/W | 0.00 | -0.07 | -0.13, -0.01 | NA | NA |
| NR/W | 1.00 | -0.10 | -0.15, -0.04 | -9.54 | -15.36, -3.72 |
| RBC (X 106/μL) | 4.00 | 0.00 | 0.00, 0.01 | 0.10 | -0.03, 0.26 |
| RBC (X 106/μL) | 5.60 | -0.01 | -0.02, 0.00 | -0.22 | -0.42, -0.02 |
| MCH (pg) | 26.7 | 0.47 | 0.43, 0.51 | 1.76 | 1.60, 1.89 |
| MCH (pg) | 31.9 | 0.32 | 0.27, 0.37 | 1.00 | 0.85, 1.15 |
| MCHC (g/dL) | 32.3 | 0.43 | 0.39, 0.50 | 1.33 | 1.20, 1.55 |
| MCHC (g/dL) | 35.9 | 0.31 | 0.18, 0.40 | 0.86 | 0.49, 1.11 |
| RETIC (X 103/μL) | 32.0 | 2.38 | 1.86, 2.97 | 7.43 | 5.80, 9.29 |
| RETIC (X 103/μL) | 129 | 7.18 | 6.09, 8.21 | 5.57 | 4.72, 6.36 |
| %R (%) | 0.80 | 0.05 | 0.04, 0.07 | 6.29 | 4.79, 8.68 |
| %R (%) | 2.30 | 0.13 | 0.12, 0.15 | 5.82 | 5.24, 6.68 |
| IRF | 0.04 | -0.01 | -0.01, -0.01 | -25.91 | -30.19, -20.67 |
| IRF | 0.37 | -0.03 | -0.04, -0.02 | -8.01 | -9.72, -6.41 |
| PLT (X 103/μL) | 10.0 | -0.02 | -0.75, 0.85 | -0.24 | -7.51, 8.53 |
| PLT (X 103/μL) | 165 | -4.58 | -5.06, -3.93 | -2.78 | -3.06, -2.38 |
| PLT (X 103/μL) | 415 | -11.94 | -13.55, -10.31 | -2.88 | -3.27, -2.48 |
| PLT (X 103/μL) | 1000 | -29.14 | -33.97, -24.59 | -2.91 | -3.40, -2.46 |
| Measurand | Critical Points | Bias | %Bias | ||
| Estimate | 95% CI | Estimate | 95% CI | ||
| MPV (fL) | 6.40 | -0.07 | -0.23, 0.06 | -1.16 | -3.61, 0.93 |
| MPV (fL) | 11.0 | -0.34 | -0.38, -0.30 | -3.06 | -3.44, -2.68 |
| %rP (%) | 1.00 | 0.40 | 0.35, 0.45 | 39.80 | 34.65, 45.18 |
| %rP (%) | 7.00 | -0.92 | -1.03, -0.80 | -13.17 | -14.70, -11.50 |
| MCHr (pg) | 29.0 | 1.30 | 1.11, 1.46 | 4.47 | 3.83, 5.04 |
| MCHr (pg) | 34.5 | 1.78 | 1.62, 1.95 | 5.17 | 4.70, 5.64 |
All Sites Combined - Estimated Bias at Critical Points (Continued)
NA = Not applicable since the critical point is zero.
16
All Sites Combined - Estimated Bias at Critical Points (Continued)
NA = Not applicable since the critical point is zero.
17
Sensitivity and Specificity 2.
The Sensitivity and Specificity study was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document CLSI H20-A2².
Sensitivity and specificity performance of the Alinity h-series System was assessed by identifying distributional abnormalities and morphological flags using blood films from venous and capillary specimens collected in K2EDTA tubes.
For this analysis, separate 2x2 tables were constructed in order to determine sensitivity for both morphological and distributional abnormalities. The sample size (N) and numbers of true positives (TP), false positives (FP), true negatives (TN), false negatives (FN), sensitivity, specificity, and efficiency are presented in the table below. All results were within the predefined acceptance criteria and found to be acceptable.
| Any Morphological Flags and/or
Distributional Abnormalities | N | TP | FP | FN | TN | Sensitivity
(95% CI) | Specificity
(95% CI) | Efficiency
(95% CI) |
|----------------------------------------------------------------|-----|----|----|-----|-------------------------------|-------------------------------|-------------------------------|------------------------|
| 674 | 255 | 84 | 63 | 272 | 80.19%
(75.38%,
84.43%) | 76.40%
(71.64%,
80.72%) | 78.19%
(74.88%,
81.25%) | |
All Sites Combined – Sensitivity and Specificity
3 Clinical and Laboratory Standards Institute (CLS). Reference Leukocyte (WBC) Differential Count (Proportional) and Evaluation of Instrumental Methods; Approved Standard-Second Edition. CLSI Document H20-A2. Wayne, PA: CLSI; 2007.
18
3. Precision (Repeatability)
Precision was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document H26-A24. Samples from 32 unique donors (16 normal and 16 pathological around medical decision points) were collected in K2EDTA tubes and tested in a minimum of 32 consecutive replicates for normal samples and a minimum of 10 consecutive replicates for pathological samples. The mean, standard deviation (SD), coefficient of variation (CV), and 95% CI were calculated for each parameter. All results met the predefined acceptance criteria and were determined to be acceptable.
4. System Reproducibility
Reproducibility was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP05-A35.
The reproducibility study was performed at three clinical sites using a single lot of Alinity h-series 29P Control (low, normal, high). Each control level was tested for 5 days with 3 runs per day and in a minimum of 2 replicates per run. The within-laboratory %CV or SD for each control level were calculated and presented in the table below. All results met the predefined acceptance criteria and were determined to be acceptable.
4 Clinical and Laboratory Standards Institute (CLSI). Validation, Verification, And Quality Assurance Of Automated Hematology Analyzers: Approved Standard - Second Edition. CLSI Document H26-A2. Wayne, PA: CLSI; 2010.
5 Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
19
| Repeatability | Between-Run | Between-Day | Within-Laboratorya | Between-Device | Reproducibility | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Measurand | Level | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| WBC (X 103/μL) | Low | 84 | 3.04 | 0.068 | 2.22 | 0.000 | 0.00 | 0.028 | 0.93 | 0.073 | 2.41 | 0.027 | 0.87 | 0.078 | 2.56 |
| Normal | 84 | 7.18 | 0.138 | 1.92 | 0.000 | 0.00 | 0.000 | 0.00 | 0.138 | 1.92 | 0.045 | 0.63 | 0.145 | 2.02 | |
| High | 84 | 16.12 | 0.185 | 1.15 | 0.000 | 0.00 | 0.000 | 0.00 | 0.185 | 1.15 | 0.000 | 0.00 | 0.185 | 1.15 | |
| NEU (X 103/μL) | Low | 84 | 1.40 | 0.052 | 3.73 | 0.014 | 0.98 | 0.000 | 0.00 | 0.054 | 3.86 | 0.034 | 2.46 | 0.064 | 4.58 |
| Normal | 84 | 3.45 | 0.097 | 2.80 | 0.015 | 0.42 | 0.000 | 0.00 | 0.098 | 2.83 | 0.060 | 1.72 | 0.115 | 3.32 | |
| High | 84 | 8.15 | 0.187 | 2.29 | 0.000 | 0.00 | 0.000 | 0.00 | 0.187 | 2.29 | 0.102 | 1.25 | 0.213 | 2.61 | |
| LYM (X 103/μL) | Low | 84 | 0.88 | 0.035 | 4.02 | 0.000 | 0.00 | 0.008 | 0.93 | 0.036 | 4.13 | 0.012 | 1.35 | 0.038 | 4.34 |
| Normal | 84 | 1.84 | 0.054 | 2.92 | 0.000 | 0.00 | 0.000 | 0.00 | 0.054 | 2.92 | 0.000 | 0.00 | 0.054 | 2.92 | |
| High | 84 | 3.57 | 0.082 | 2.29 | 0.000 | 0.00 | 0.000 | 0.00 | 0.082 | 2.29 | 0.000 | 0.00 | 0.082 | 2.29 | |
| MONO (X 103/μL) | Low | 84 | 0.33 | 0.024 | 7.18 | 0.000 | 0.00 | 0.005 | 1.65 | 0.024 | 7.36 | 0.007 | 2.15 | 0.025 | 7.67 |
| Normal | 84 | 0.80 | 0.051 | 6.35 | 0.000 | 0.00 | 0.000 | 0.00 | 0.051 | 6.35 | 0.000 | 0.00 | 0.051 | 6.35 | |
| High | 84 | 1.84 | 0.073 | 4.00 | 0.047 | 2.57 | 0.000 | 0.00 | 0.087 | 4.75 | 0.000 | 0.00 | 0.087 | 4.75 | |
| EOS (X 103/μL) | Low | 84 | 0.07 | 0.010 | 13.91 | 0.000 | 0.00 | 0.002 | 2.76 | 0.010 | 14.18 | 0.000 | 0.00 | 0.010 | 14.18 |
| Normal | 84 | 0.20 | 0.014 | 7.20 | 0.006 | 2.77 | 0.000 | 0.00 | 0.015 | 7.72 | 0.000 | 0.00 | 0.015 | 7.72 | |
| High | 84 | 0.49 | 0.025 | 5.16 | 0.010 | 2.13 | 0.000 | 0.00 | 0.027 | 5.59 | 0.003 | 0.55 | 0.027 | 5.61 |
All Sites Combined – Reproducibility Study
NA=Not Applicable; %CVs are not meaningful when measurand result approaches zero.
4 Reproducibility contains repeatability, between-run, between-day, and between-device variance components.
20
| Repeatability | Between-Run | Between-Day | Within-Laboratorya | Between-Device | Reproducibility | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Measurand | Level | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| BASO (X 103/μL) | Low | 84 | 0.03 | 0.008 | 24.23 | 0.005 | 14.55 | 0.001 | 2.04 | 0.009 | 28.34 | 0.000 | 0.00 | 0.009 | 28.34 |
| BASO (X 103/μL) | Normal | 84 | 0.06 | 0.012 | 18.37 | 0.000 | 0.00 | 0.000 | 0.00 | 0.012 | 18.37 | 0.000 | 0.00 | 0.012 | 18.37 |
| BASO (X 103/μL) | High | 84 | 0.15 | 0.017 | 10.71 | 0.007 | 4.57 | 0.000 | 0.00 | 0.018 | 11.64 | 0.003 | 2.14 | 0.018 | 11.84 |
| IG (X 103/μL) | Low | 84 | 0.33 | 0.024 | 7.40 | 0.000 | 0.00 | 0.000 | 0.00 | 0.024 | 7.40 | 0.010 | 2.96 | 0.026 | 7.97 |
| IG (X 103/μL) | Normal | 84 | 0.82 | 0.047 | 5.71 | 0.000 | 0.00 | 0.013 | 1.62 | 0.049 | 5.94 | 0.017 | 2.06 | 0.052 | 6.29 |
| IG (X 103/μL) | High | 84 | 1.92 | 0.079 | 4.09 | 0.061 | 3.16 | 0.000 | 0.00 | 0.099 | 5.17 | 0.059 | 3.08 | 0.116 | 6.02 |
| NRBC (X 103/μL) | Low | 84 | 0.00 | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA |
| NRBC (X 103/μL) | Normal | 84 | 0.00 | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA |
| NRBC (X 103/μL) | High | 84 | 2.34 | 0.062 | 2.64 | 0.000 | 0.00 | 0.000 | 0.00 | 0.062 | 2.64 | 0.016 | 0.69 | 0.064 | 2.73 |
| RBC (X 106/μL) | Low | 84 | 2.67 | 0.018 | 0.69 | 0.000 | 0.00 | 0.006 | 0.23 | 0.019 | 0.73 | 0.000 | 0.00 | 0.019 | 0.73 |
| RBC (X 106/μL) | Normal | 84 | 4.13 | 0.028 | 0.68 | 0.000 | 0.00 | 0.000 | 0.00 | 0.028 | 0.68 | 0.019 | 0.46 | 0.034 | 0.82 |
| RBC (X 106/μL) | High | 84 | 5.16 | 0.047 | 0.92 | 0.000 | 0.00 | 0.008 | 0.15 | 0.048 | 0.93 | 0.085 | 1.65 | 0.098 | 1.90 |
| HGB (g/dL) | Low | 84 | 7.11 | 0.041 | 0.57 | 0.017 | 0.25 | 0.000 | 0.00 | 0.044 | 0.62 | 0.048 | 0.68 | 0.065 | 0.92 |
| HGB (g/dL) | Normal | 84 | 11.34 | 0.066 | 0.58 | 0.000 | 0.00 | 0.000 | 0.00 | 0.066 | 0.58 | 0.048 | 0.42 | 0.082 | 0.72 |
| HGB (g/dL) | High | 84 | 16.37 | 0.094 | 0.57 | 0.017 | 0.11 | 0.020 | 0.12 | 0.097 | 0.60 | 0.000 | 0.00 | 0.097 | 0.60 |
NA=Not Applicable; %CVs are not meaningful when measurand result approaches zero.
ª Reproducibility contains repeatability, between-run, between-day, and between-device variance components.
21
| Measurand | Level | N | Mean | Repeatability | Between-Run | Between-Day | Within-Laboratoryᵃ | Between-Device | Reproducibility | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| HCT (%) | Low | 84 | 22.64 | 0.179 | 0.79 | 0.000 | 0.00 | 0.107 | 0.47 | 0.209 | 0.92 | 0.062 | 0.27 | 0.218 | 0.96 |
| Normal | 84 | 35.88 | 0.269 | 0.75 | 0.000 | 0.00 | 0.038 | 0.11 | 0.272 | 0.76 | 0.244 | 0.68 | 0.366 | 1.02 | |
| High | 84 | 49.80 | 0.468 | 0.94 | 0.000 | 0.00 | 0.155 | 0.31 | 0.493 | 0.99 | 0.897 | 1.80 | 1.023 | 2.05 | |
| MCV (fL) | Low | 84 | 84.68 | 0.120 | 0.14 | 0.185 | 0.22 | 0.248 | 0.29 | 0.332 | 0.39 | 0.320 | 0.38 | 0.461 | 0.54 |
| Normal | 84 | 86.93 | 0.212 | 0.24 | 0.153 | 0.18 | 0.173 | 0.20 | 0.313 | 0.36 | 0.247 | 0.28 | 0.399 | 0.46 | |
| High | 84 | 96.48 | 0.092 | 0.10 | 0.116 | 0.12 | 0.270 | 0.28 | 0.308 | 0.32 | 0.201 | 0.21 | 0.368 | 0.38 | |
| MCH (pg) | Low | 84 | 26.58 | 0.231 | 0.87 | 0.076 | 0.29 | 0.069 | 0.26 | 0.253 | 0.95 | 0.154 | 0.58 | 0.296 | 1.11 |
| Normal | 84 | 27.48 | 0.240 | 0.88 | 0.000 | 0.00 | 0.000 | 0.00 | 0.240 | 0.88 | 0.041 | 0.15 | 0.244 | 0.89 | |
| High | 84 | 31.72 | 0.344 | 1.08 | 0.000 | 0.00 | 0.075 | 0.24 | 0.352 | 1.11 | 0.495 | 1.56 | 0.607 | 1.92 | |
| MCHC (g/dL) | Low | 84 | 31.39 | 0.292 | 0.93 | 0.000 | 0.00 | 0.154 | 0.49 | 0.330 | 1.05 | 0.251 | 0.80 | 0.415 | 1.32 |
| Normal | 84 | 31.61 | 0.310 | 0.98 | 0.000 | 0.00 | 0.000 | 0.00 | 0.310 | 0.98 | 0.150 | 0.47 | 0.344 | 1.09 | |
| High | 84 | 32.88 | 0.363 | 1.10 | 0.000 | 0.00 | 0.112 | 0.34 | 0.380 | 1.16 | 0.563 | 1.71 | 0.679 | 2.07 | |
| RDW (%) | Low | 84 | 13.26 | 0.084 | 0.63 | 0.000 | 0.00 | 0.033 | 0.25 | 0.090 | 0.68 | 0.670 | 5.05 | 0.676 | 5.10 |
| Normal | 84 | 13.32 | 0.096 | 0.72 | 0.000 | 0.00 | 0.021 | 0.16 | 0.098 | 0.74 | 0.705 | 5.29 | 0.711 | 5.34 | |
| High | 84 | 12.37 | 0.049 | 0.39 | 0.031 | 0.25 | 0.035 | 0.29 | 0.068 | 0.55 | 0.621 | 5.02 | 0.625 | 5.05 |
NA=Not Applicable; %CVs are not meaningful when measurand result approaches zero.
- Reproducibility contains repeatability, between-run, between-day, and between-device variance components.
22
| Measurand | Level | N | Mean | Repeatability | Between-Run | Between-Day | Within-Laboratorya | Between-Device | Reproducibility | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| RETIC ( $X 10^3/μL$ ) | Low | 84 | 216.24 | 3.142 | 1.45 | 0.000 | 0.00 | 1.132 | 0.52 | 3.340 | 1.54 | 4.535 | 2.10 | 5.632 | 2.60 |
| Normal | 84 | 153.55 | 3.478 | 2.26 | 0.805 | 0.52 | 1.374 | 0.89 | 3.825 | 2.49 | 7.441 | 4.85 | 8.367 | 5.45 | |
| High | 84 | 132.30 | 4.172 | 3.15 | 0.000 | 0.00 | 0.000 | 0.00 | 4.172 | 3.15 | 10.734 | 8.11 | 11.517 | 8.71 | |
| IRF | Low | 84 | 0.33 | 0.011 | 3.30 | 0.000 | 0.00 | 0.008 | 2.52 | 0.014 | 4.15 | 0.050 | 15.31 | 0.052 | 15.86 |
| Normal | 84 | 0.27 | 0.011 | 4.23 | 0.000 | 0.00 | 0.005 | 2.02 | 0.013 | 4.69 | 0.028 | 10.30 | 0.031 | 11.32 | |
| High | 84 | 0.19 | 0.009 | 4.56 | 0.003 | 1.48 | 0.000 | 0.00 | 0.009 | 4.80 | 0.004 | 2.28 | 0.010 | 5.31 | |
| PLT ( $X 10^3/μL$ ) | Low | 84 | 73.78 | 1.977 | 2.68 | 0.000 | 0.00 | 0.508 | 0.69 | 2.041 | 2.77 | 1.317 | 1.79 | 2.429 | 3.29 |
| Normal | 84 | 225.19 | 3.454 | 1.53 | 1.380 | 0.61 | 0.216 | 0.10 | 3.726 | 1.65 | 1.257 | 0.56 | 3.932 | 1.75 | |
| High | 84 | 478.12 | 7.653 | 1.60 | 0.000 | 0.00 | 2.889 | 0.60 | 8.180 | 1.71 | 3.997 | 0.84 | 9.105 | 1.90 | |
| MPV (fL) | Low | 84 | 9.55 | 0.070 | 0.73 | 0.000 | 0.00 | 0.000 | 0.00 | 0.070 | 0.73 | 0.022 | 0.23 | 0.073 | 0.77 |
| Normal | 84 | 9.59 | 0.041 | 0.43 | 0.000 | 0.00 | 0.008 | 0.08 | 0.042 | 0.44 | 0.022 | 0.23 | 0.047 | 0.49 | |
| High | 84 | 9.60 | 0.031 | 0.32 | 0.021 | 0.22 | 0.000 | 0.00 | 0.037 | 0.39 | 0.005 | 0.05 | 0.038 | 0.39 | |
| %rP (%) | Low | 84 | 9.77 | 0.439 | 4.49 | 0.000 | 0.00 | 0.030 | 0.31 | 0.440 | 4.50 | 0.000 | 0.00 | 0.440 | 4.50 |
| Normal | 84 | 8.82 | 0.140 | 1.59 | 0.095 | 1.08 | 0.017 | 0.20 | 0.170 | 1.93 | 0.000 | 0.00 | 0.170 | 1.93 | |
| High | 84 | 9.00 | 0.105 | 1.16 | 0.000 | 0.00 | 0.055 | 0.62 | 0.119 | 1.32 | 0.000 | 0.00 | 0.119 | 1.32 |
NA=Not Applicable; %CVs are not meaningful when measurand result approaches zero.
4 Reproducibility contains repeatability, between-run, between-day, and between-device variance components.
23
| Measurand | Level | N | Mean | Repeatability | Between-Run | Between-Day | Within-Laboratoryª | Between-Device | Reproducibility | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| %B (%) | Low | 84 | 1.04 | 0.251 | 24.03 | 0.154 | 14.79 | 0.032 | 3.03 | 0.296 | 28.38 | 0.000 | 0.00 | 0.296 | 28.38 |
| Normal | 84 | 0.90 | 0.164 | 18.32 | 0.000 | 0.00 | 0.000 | 0.00 | 0.164 | 18.32 | 0.000 | 0.00 | 0.164 | 18.32 | |
| High | 84 | 0.96 | 0.100 | 10.39 | 0.049 | 5.09 | 0.000 | 0.00 | 0.111 | 11.57 | 0.020 | 2.06 | 0.113 | 11.75 | |
| %IG (%) | Low | 84 | 10.78 | 0.780 | 7.24 | 0.000 | 0.00 | 0.000 | 0.00 | 0.780 | 7.24 | 0.450 | 4.17 | 0.900 | 8.35 |
| Normal | 84 | 11.46 | 0.572 | 4.99 | 0.175 | 1.53 | 0.078 | 0.68 | 0.603 | 5.26 | 0.322 | 2.81 | 0.684 | 5.97 | |
| High | 84 | 11.92 | 0.465 | 3.90 | 0.378 | 3.17 | 0.000 | 0.00 | 0.599 | 5.03 | 0.379 | 3.18 | 0.709 | 5.95 | |
| NR/W | Low | 84 | 0.00 | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA |
| Normal | 84 | 0.00 | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA | 0.000 | NA | |
| High | 84 | 14.53 | 0.384 | 2.64 | 0.000 | 0.00 | 0.035 | 0.24 | 0.385 | 2.65 | 0.093 | 0.64 | 0.396 | 2.73 | |
| %R (%) | Low | 84 | 8.09 | 0.120 | 1.49 | 0.000 | 0.00 | 0.000 | 0.00 | 0.120 | 1.49 | 0.173 | 2.14 | 0.211 | 2.60 |
| Normal | 84 | 3.72 | 0.078 | 2.10 | 0.027 | 0.73 | 0.026 | 0.70 | 0.087 | 2.33 | 0.198 | 5.32 | 0.216 | 5.81 | |
| High | 84 | 2.57 | 0.084 | 3.28 | 0.000 | 0.00 | 0.000 | 0.00 | 0.084 | 3.28 | 0.254 | 9.90 | 0.268 | 10.43 |
NA=Not Applicable; %CVs are not meaningful when measurand result approaches zero.
4 Reproducibility contains repeatability, between-run, between-day, and between-device variance components.
24
5. Linearity
Linearity was evaluated based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP06 2nd edition6.
Linearity for RBC, HGB, and NRBC was determined using whole blood to span the analytical measuring interval of each measurand. Linearity for WBC, PLT, and RETIC was determined using commercially available linearity kits. For each measurand, the testing minimally included:
- 9 levels
- 4 replicates of each level
- 1 instrument
- 1 set of reagent lots
A weighted linear regression analysis was used to assess linearity for each measurand. Results are presented in the table below. All results met the predefined acceptance criteria and were determined to be acceptable.
| Measurand | Linear Range |
|---|---|
| RBC | 0.00 – $8.08 \times 10^6$ /μL |
| HGB | 0.04 – 24.14 g/dL |
| NRBC | 0.00 – $26.10 \times 10^3$ /μL |
| WBC | 0.00 – $449 \times 10^3$ /μL |
| PLT | 0.06 – $5325 \times 10^3$ /μL |
| RETIC | 0.05 – $644 \times 10^3$ /μL |
6 Clinical and Laboratory Standards Institute (CLS). Evaluation of the Linearity of Quantitative Measurement Procedures. 2nd edition. CLSI Document EP06. Wayne, PA: CLSI; 2020.
25
6. Carryover
Alinity hq susceptibility to potential carryover was evaluated based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document H26-A2.7 Venous whole blood specimens were collected in K2EDTA tubes. For each measurand, a minimum of 4 carryover runs was completed at each of 4 testing sites for a minimum of 16 total carryover runs per measurand, where each run consisted of testing a high target specimen in 3 replicates followed by testing a low target specimen in 3 replicates. All results met the predefined acceptance criteria and were determined to be acceptable.
Potentially Interfering Substances Study 7.
The susceptibility of the Alinity h-series System to interference in the presence of hemoglobin, triglycerides, bilirubin, cholesterol, elevated WBCs, elevated RBCs, elevated PLTs, and microcytic RBCs was tested in samples collected in K2EDTA tubes. Results are presented in the table below. All results met the predefined acceptance criteria and were determined to be acceptable.
| Interferent | Result Level | Measurand Impacted |
|---|---|---|
| Hemoglobin | 1.0 g/dL | WBC, RBC, MCV, PLT, RETIC |
| 1.15 g/dL | WBC, RBC, HGB, MCV, RETIC | |
| Triglyceride | 0.63 g/dL | PLT |
| 0.080 g/dL | WBC, RBC, HGB, PLT, RETIC | |
| Bilirubin - unconjugated | 0.040 g/dL | MCV |
| Bilirubin - conjugated | 0.080 g/dL | WBC, RBC, HGB, MCV, PLT, RETIC |
| Cholesterol | 0.40 g/dL | WBC, RBC, HGB, MCV, RETIC |
| 0.50 g/dL | PLT | |
| Elevated WBCs | 99.0 x 103 cells/µL | RBC, PLT, HGB, MPV |
| Elevated RBCs | No interference was observed across the measuring range | |
| Elevated PLTs | 2840 x 103 cells/µL | WBC, RBC, HGB, MPV |
| Microcytic RBCs | Microcytosis (MCV 7 Clinical and Laboratory Standards Institute (CLSI). Validation, Verification, And Quality Assurance Of Automated Hematology Analyzers; Approved Standard - Second Edition. CLSI Document H26-A2. Wayne, PA: CLSI; 2010. |
26
VIII. Other Supportive Instrument Performance Data
Limits of Blank, Detection, and Quantitation (LoB, LoD, and LoO) 1.
Limits of Blank, Detection, and Quantitation were established for the measurands WBC, RBC, HGB, and PLT based on guidance from the Clinical and Laboratory Standards Institute (CLSI) documents EP17-A28 and H26-A2°.
Testing was conducted over a minimum of 3 days using a minimum of 2 unique samples per day on each of 2 test selections (CBC+Diff and CBC+Diff+Retic) in a minimum of 5 replicates using each of the 2 sets of reagent lots. The maximum observed limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized in the table below. All results met the predefined acceptance criteria and were determined to be acceptable.
| Measurand | Results
LoB | Results
LoD | Results
LoQ |
|---------------|----------------|----------------|----------------|
| WBC (x103/μL) | 0.01 | 0.02 | 0.03 |
| RBC (x106/μL) | 0.00 | 0.01 | 0.01 |
| HGB (g/dL) | 0.08 | 0.11 | 0.05 |
| PLT (x103/μL) | 0.15 | 0.38 | 0.29 |
Limits of Blank, Detection, and Quantitation (LoB, LoD, and LoQ)
8 Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurent Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.
9 Clinical and Laboratory Standards Institute (CLS). Validation, Verification, And Quality Assurance Of Automated Hematology Analyzers; Approved Standard - Second Edition. CLSI Document H26-A2. Wayne, PA: CLSI; 2010.
27
2. Specimen Stability
For venous specimen stability, a minimum of 10 abnormal and 10 normal venous whole blood specimens K2EDTA and K3EDTA tubes. Each specimen was tested in a minimum of 2 replicates. For capillary specimen stability, a minimum of 20 normal whole blood specimens were collected in K2EDTA and K3EDTA tubes. Each specimen was tested in a minimum of 1 replicate. All samples were tested within 4 hours (baseline) of specimen collection. Samples stored at Refrigerated Temperature (2-8℃) were tested at up to 24 hours after specimen collection. Samples stored at Room Temperature (18-26℃) were tested at up to 48 hours after specimen collection. The results were used to support the information provided in the system labeling for venous and capillary specimen stability.
Anticoagulant Comparability (K3EDTA versus K2EDTA) 3.
Anticoagulant Comparability (K3EDTA versus K2EDTA) was evaluated based on guidance from CLSI EP35 1st ed19. A total of 199 unique adult and pediatric donor sets covering relevant medical decision levels and reference ranges and spanning the analytical measurement ranges to the extent possible were tested in 2 replicates for each measurand. The performance between the anticoagulant tube type (K3EDTA) and anticoagulant tube type (K2EDTA) was compared.
Comparability between the anticoagulants was assessed based on the mean difference or % difference and a regression analysis using either a Passing-Bablok or Deming regression model. All reportable parameters that were evaluated met their predefined bias acceptance criteria.
Microtainer Capillary versus Microtube for Automated Process (MAP) 4.
Comparability between the K2EDTA Microtainer Capillary tube versus K2EDTA Microtainer Microtube for Automated Process (MAP) was evaluated
10 Clinical and Laboratory Standards Institute (CLS). Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures. 1st ed. CLSI Guideline EP35-A. Wayne, PA: CLSI; 2019.
28
based on guidance from CLSI document EP35 1* ed11. A total of 44 unique donor sets (normal whole blood specimens) were collected in K2EDTA Microtainer Capillary and Microtainer Microtube for Automated Process (MAP) blood collection tubes. Each specimen was tested in 1 replicate in the open-tube processing mode for each measurand.
Comparability between the capillary tube types was assessed based on the mean difference or % difference and a regression analysis using either a Passing-Bablok or Deming regression model. All reportable parameters that were evaluated met their predefined bias acceptance criteria.
Matrix Comparability (Capillary versus Venous) 5.
Matrix Comparability (Capillary versus Venous) was evaluated based on guidance from CLSI EP35 1* ed.12 A total of 76 unique venous and capillary donor sets (normal and abnormal whole blood specimens) were collected in Microtainer Microtube for Automated Process (MAP) Microtubes (capillary specimens) and standard K2EDTA tubes (venous specimens). Each specimen was tested in 2 replicates for each measurand.
Comparability between capillary and venous matrices was assessed based on the mean difference or % difference and a regression analysis using either a Passing-Bablok or Deming regression model. All reportable parameters that were evaluated met their predefined bias acceptance criteria.
Sample/Tube Processing Mode Comparability (Open Mode versus Closed 6. Mode)
Sample processing mode comparability was evaluated based on guidance from CLSI EP35 1* ed.11 A total of 226 unique venous specimens covering relevant medical decision levels and reference ranges and spanning the analytical
11 Clinical and Laboratory Standards Institute (CLS). Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures. 1st ed. CLSI Guideline EP35-A. Wayne, PA: CLSI; 2019.
12 Clinical and Laboratory Standards Institute (CLSI). Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures. 1st ed. CLSI Guideline EP35. Wayne, PA: CLSI; 2019.
29
measurement ranges to the extent possible were collected in K2EDTA tubes. Each specimen was tested in 2 replicates in the closed-tube and open-tube processing modes for each measurand.
Comparability between the sample/tube processing modes was assessed based on the mean difference or % difference and a regression analysis using either a Passing-Bablok or Deming regression model. All reportable parameters that were evaluated met their predefined bias acceptance criteria.
Reference Intervals (Expected Values) 7.
The study was performed based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP28-A3c13 to establish adult (> 21 years old) reference intervals for male and female populations and pediatric (≤ 21 years old) reference intervals for all subgroups (neonate, infant, child, and adolescent). Reference intervals were established by evaluating venous or capillary whole blood specimens collected in K2EDTA tubes from apparently healthy subjects.
A total of 261 unique venous and 1 capillary whole blood specimens collected from 126 male and 136 female adult subjects were tested in a minimum of 1 replicate to establish adult reference intervals. A total of 360 venous or capillary specimens from pediatric sub-populations: 61 neonates (birth to 1 month); 68 infant (> 1 month to 2 years old), 109 child (> 2 to 12 years old), and 122 adolescents (> 12 to 21 years old) were tested in 1 replicate to establish pediatric reference intervals for each measurand.
13 Clinical and Laboratory Standards Institute (CLS). Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory, 3rd Ed CLSI Guideline EP28-A3c. Wayne, PA: CLSI; 2019.
30
IX. Conclusion
The results presented in this 510(k) Pre-market Notification demonstrate that the performance of the subject device, Alinity h-series System, is substantially equivalent to the predicate device, Sysmex® XN-Series (XN-10, XN-20).
The similarities and differences between the subject device and predicate device are presented in Section 5-VI.
There is no known potential adverse effect to the operator when using the subject device, Alinity h-series System according to its Operations Manual.