(214 days)
Not Found
No
The summary describes a photometric measurement using an algorithm to translate light measurements into hemoglobin concentration. This is a standard signal processing technique and does not indicate the use of AI or ML. There is no mention of AI, ML, or related concepts like training data or complex pattern recognition.
No
The device is intended for quantitative determination of hemoglobin for diagnostic purposes, not for treating any condition.
Yes.
The device is specifically stated to be "for professional in vitro diagnostic use only," which directly indicates its function as a diagnostic tool.
No
The device description explicitly states that the system consists of an analyzer (hardware), single-use microcuvettes (consumable hardware), and a power supply (hardware). While it uses an algorithm for calculation, it is fundamentally a hardware-based photometric measurement system.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "The HemoCue® Hb 801 System is for professional in vitro diagnostic use only."
- Intended Use: The device is intended for the "quantitative determination of hemoglobin in capillary or venous whole blood." This is a measurement performed on a biological sample in vitro (outside the body) to provide diagnostic information.
- Device Description: The description details how the device analyzes a blood sample using a microcuvette and an analyzer to determine hemoglobin concentration. This process is characteristic of an in vitro diagnostic test.
- Performance Studies: The document describes various analytical performance studies conducted on blood samples (precision, linearity, detection limit, interference, method comparison), which are standard for validating an IVD device.
N/A
Intended Use / Indications for Use
The HemoCue® Hb 801 System is intended for the quantitative determination of hemoglobin in capillary or venous whole blood (K2EDTA and Li-Heparin) in point-of-care settings. The HemoCue® Hb 801 System is intended to be used to determine the hemoglobin concentration for adults, adolescents, children, and infants above 1 month old. The HemoCue® Hb 801 System is for professional in vitro diagnostic use only.
Product codes (comma separated list FDA assigned to the subject device)
GKR
Device Description
The HemoCue® Hb 801 System provides a direct reading of the hemoglobin concentration in a sample using specially designed, single use microcuvette and an analyzer. The system can be used by non-laboratory personnel.
The HemoCue® Hb 801 System consists of the following parts:
- An analyzer supporting the following features:
- Photometric determination of hemoglobin
- Presentation of results on a display
- Wired and wireless communication (USB and Bluetooth)
- Power supply by power adapter, chargeable or non- chargeable batteries
- Single use microcuvettes (test consumable)
- Labeling:
- Operating Manual
- Package Insert
- Quick reference Guide
- Labels
The microcuvette serves both as a pipette and as a measuring cuvette. No dilution or other preparation of the blood sample is required before filling of the microcuvette. A whole blood sample of approximately 10 uL is drawn into the cavity in the microcuvette by capillary action.
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
Adults, adolescents, children, and infants above 1 month old.
Intended User / Care Setting
Professional in vitro diagnostic use only, in point-of-care settings. The system can be used by non-laboratory personnel.
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
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
- Precision (Whole Blood):
- Multi-microcuvette study: Performed at a single site over 5 operating days. Six hemoglobin levels analyzed with 5 separate runs testing 5 replicates with three lots of HemoCue® Hb 801 Microcuvette and one HemoCue® Hb 801 Analyzer. Each blood sample analyzed with 25 replicates per microcuvette lot, providing 75 measurements for each level. SD and CV were calculated for repeatability, within-laboratory precision, and reproducibility.
- Multi-site study: Performed at 3 sites during 5 operating days. Six hemoglobin levels analyzed with five separate runs testing five replicates at each site using three HemoCue® Hb 801 Analyzers and one lot of HemoCue® Hb 801 Microcuvette. Each blood sample analyzed with 25 replicates using one analyzer per site, providing 75 measurements for each level. SD and CV were calculated for repeatability, within-laboratory precision, and reproducibility.
- Precision (Quality Control Material): Conducted at three sites over 20 operating days using three HemoCue® Hb 801 Microcuvette lots (one lot per site), three HemoCue® Hb 801 Analyzers (one analyzer per site), and 1 lot of control material (level 1= low, level 2= medium, level 3= high). Each control set run in duplicate twice daily for 20 days, by 10 operators (minimum 2 operators per site). A total of 240 measurements (80 per level) were generated at each site. SD and CV calculated for repeatability, between-run, between-day, within laboratory precision, and combined reproducibility for all sites were within defined acceptance criteria.
- Linearity: Used hemoglobin concentration prepared from a single, venous whole blood sample. A total of 9 hemoglobin concentrations (0.50, 3.78, 7.05, 10.33, 13.60, 16.88, 20.15, 23.43, 26.70 g/dL) spanning the claimed measuring range (1.0-25.6 g/dL) were tested with 15 replicates and analyzed using three HemoCue® Hb 801 Analyzers (5 replicates/analyzer) and one lot of HemoCue® Hb 801 Microcuvette. Statistical analysis was performed separately for each analyzer using polynomial regression analysis. The HemoCue® Hb 801 System is linear in the range 1.0-25.6 g/dL with fulfilled acceptance criteria for the non-linear error.
- Shelf-life: Determined using 3 lots of HemoCue® Hb 801 Microcuvette. At every analysis run, microcuvettes were tested with 3 venous K2EDTA whole blood samples from 3 different subjects at each Hb level (a total of 9 fresh blood samples per analysis run). Shelf life determined to 6 months (at time of premarket notification, will be extended).
- Detection limit:
- Limit of Blank (LoB): Plasma samples obtained from four individual whole blood samples. Study conducted with 3 HemoCue® Hb 801 Analyzers and 2 lots of HemoCue® Hb 801 Microcuvette over 4 operating days. One sample analyzed each day at 3 different runs with two replicates/analyzer per run, totaling 72 replicates/microcuvette lot. LoB determined to be 0.26 g/dL.
- Limit of Detection (LoD): Four K2EDTA whole blood samples collected from different subjects with Hb-levels within 1-5 times LoB value (0.46 - 1.0 g/dL). Study conducted over 4 operating days using 3 HemoCue® Hb 801 Analyzers and 2 lots of HemoCue® Hb 801 Microcuvette. Four samples analyzed with one sample each day at 3 different runs with 2 replicates/analyzer per run, totaling 72 replicates/microcuvette lot. LoD determined to be 0.3 g/dL.
- Limit of Quantification (LoQ): Four K2EDTA whole blood samples collected from different subjects with Hb-levels slightly above LoD (0.40-0.52 g/dL). Study conducted with 3 HemoCue® Hb 801 Analyzers and 2 lots of HemoCue® Hb 801 Microcuvette over 4 operating days. Samples analyzed within the interval of LoD+0.4 g/L, with one sample each day at 3 different runs with 3 replicates/analyzer per run, totaling 108 replicates/microcuvette lot. LoQ determined to be 0.5 g/dL.
- Analytical specificity (Interference): Evaluated the effect of potential interferents on the HemoCue® Hb 801 System. Study performed by adjusting Hb-levels of K2EDTA whole blood samples. For leucocytes, platelets, and certain patient conditions (Sickle cells, Polycythemia vera, Thalassemia/hypochromia and Anemia), interference was evaluated using a comparative procedure between the HemoCue® Hb 801 System and ICSH as a reference method. No interference found for Acetaminophen, Ascorbic acid, Creatinine, HbCO, HbO2, Hemolysis, Ibuprofen, MetHb, Platelets, Total protein, Salicylic acid, Simvastatin, Tetracycline, Triglycerides, Urea, Uric acid, Warfarin at specified concentrations. Interfering concentrations were identified for Conjugated bilirubin, Unconjugated bilirubin, Intralipid, and Leucocytes.
- Within Measurement Equivalence Tests (Anticoagulants): Demonstrated equivalence between K2EDTA and Li-Heparin. Conducted at two sites, over 5 operating days at each site, using one HemoCue® Hb 801 Analyzer and one lot of HemoCue® Hb 801 Microcuvettes. Each of 120 subjects provided one fresh venous K2EDTA and one fresh venous Li-Heparin whole blood sample. Additional samples collected from 11 subjects to adjust Hb value to high and low Hb values. Regression analysis performed. Both K2EDTA and Lithium Heparin samples fulfilled acceptance criteria regarding correlation and bias.
- Within Measurement Equivalence Tests (Capillary vs. Venous Sample): Verified equivalency of venous and capillary whole blood samples. Capillary and venous whole blood samples collected from 40 subjects. Additional data points from 212 subjects were taken from the method comparison study. Regression analysis performed. Both venous and capillary samples were within the defined acceptance criteria and showed equivalency.
- Method Comparison Study (with predicate device): Evaluated accuracy of the HemoCue® Hb 801 System in point-of-care facilities. Performed at five primary care settings in the US over 73 operating days. Total of 264 venous and 233 capillary whole blood samples tested using the HemoCue® Hb 801 System and the predicate device, HemoCue® Hb 301 System (in duplicate). Studies performed on six HemoCue® Hb 801 Analyzers and four lots of HemoCue® Hb 801 Microcuvette by 13 operators. 6% of samples (28/497) were adjusted (contrived). Linear regression analysis demonstrated comparable performance.
- K2EDTA Venous (n=264): Slope 1.00 (0.99 to 1.01 CI), Intercept -0.14 (-0.26 to -0.03 CI), r=1.00.
- Capillary (n=233): Slope 1.07 (1.02 to 1.12 CI), Intercept -0.91 (-1.54 to -0.28 CI), r=0.96.
- Pediatric samples (n=71): Tested at one European clinical laboratory site over 7 operating days. Analyzed with 2 replicates on subject device, 2 replicates on predicate device, and 3 replicates with reference method ICSH.
- Subject device vs. ICSH: slope 0.95, correlation coefficient (r) 0.99.
- Subject device vs. predicate device: slope 0.97, correlation coefficient (t) 0.99.
- Reference Range Verification: Verified by testing whole blood specimens collected and tested at 5 point-of-care locations in the US on the HemoCue® Hb 801 System. The study results verified that the reference ranges data on the HemoCue® Hb 801 System for the subgroups fall within the defined reference ranges below.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Precision: SD (g/dL), CV (%), Repeatability, Within Lab Precision, Reproducibility.
- Linearity: Non-linear error (fulfilled acceptance criteria).
- Detection Limits: LoB (0.26 g/dL), LoD (0.3 g/dL), LoQ (0.5 g/dL).
- Method Comparison: Slope, Intercept, Correlation coefficient (r).
- K2EDTA Venous: Slope 1.00, r=1.00.
- Capillary: Slope 1.07, r=0.96.
- Pediatric samples (vs. ICSH): slope 0.95, r=0.99.
- Pediatric samples (vs. predicate): slope 0.97, r=0.99.
- Reference Ranges:
- Infant (>1 month - 2 years): 9.4 - 14.1 Hb, g/dL
- Child (>2 - 12 years): 11.0 - 15.5 Hb, g/dL
- Adolescent (>12 - 21 years): 10.9 - 15.1 Hb, g/dL
- Adult Male (>21 years): 13.0 - 17.0 Hb, g/dL
- Adult Female (>21 years): 12.0 - 15.0 Hb, g/dL
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.
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.
Not Found
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
§ 864.5620 Automated hemoglobin system.
(a)
Identification. An automated hemoglobin system is a fully automated or semi-automated device which may or may not be part of a larger system. The generic type of device consists of the reagents, calibrators, controls, and instrumentation used to determine the hemoglobin content of human blood.(b)
Classification. Class II (performance standards).
0
Image /page/0/Picture/0 description: The image shows the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. Food & Drug Administration" in blue.
February 1, 2019
HemoCue AB Maria Fagerberg Director Regulatory Affairs Kuvettgatan 1 Angelholm, Sweden SE-26271
Re: K181751
Trade/Device Name: HemoCue Hb 801 System Regulation Number: 21 CFR 864.5620 Regulation Name: Automated hemoglobin system Regulatory Class: Class II Product Code: GKR Dated: June 27, 2018 Received: July 2, 2018
Dear Maria Fagerberg:
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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
1
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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice
(https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Leonthena R. Carrington -S
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K181751
Device Name HemoCue® Hb 801 System
Indications for Use (Describe)
The HemoCue® Hb 801 System is intended for the quantitative determination of hemoglobin in capillary or venous whole blood (K2EDTA and Li-Heparin) in point-of-care settings. The HemoCue® Hb 801 System is intended to be used to determine the hemoglobin concentration for adults, adolescents, children, and infants above 1 month old. The HemoCue® Hb 801 System is for professional in vitro diagnostic use only.
| 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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Enclosure 1
510(k) Summary
4
1. Submitter and contact information
Submitter:
| Company Name: | HemoCue AB |
|---|---|
| ER Number: | 3003044483 |
| Address: | Kuvettgatan 1 |
| SE-262 71 | |
| Sweden |
Official contact person:
| Name: | Maria Fagerberg |
|---|---|
| Function: | Director Regulatory Affairs |
| E-mail: | maria.fagerberg@hemocue.se |
| Phone: | +46 431 48 13 46 |
| Fax: | +46 431 48 12 25 |
Secondary contact:
| Name: | Andrijana Kankaras |
|---|---|
| Function: | Regulatory Affairs Specialist |
| Phone: | +46 431 48 12 26 |
| Fax: | +46 431 48 12 25 |
| E-mail: | andrijana.kankaras@hemocue.se |
Date of preparation:
Date: June 27, 2018
2. Device information
| Proprietary name: | HemoCue® Hb 801 System |
|---|---|
| Common name: | Hemoglobin analyzing system |
| Regulation: | Automated hemoglobin system (21 CFR § 864.5620 |
| Product code: | GKR |
| Classification: | Class II |
| Common name: | Hemoglobin analyzing system |
| Panel: | Hematology |
5
3. Device description
The HemoCue® Hb 801 System provides a direct reading of the hemoglobin concentration in a sample using specially designed, single use microcuvette and an analyzer. The system can be used by non-laboratory personnel.
The HemoCue® Hb 801 System consists of the following parts:
- An analyzer supporting the following features: .
- O Photometric determination of hemoglobin
- Presentation of results on a display O
- O Wired and wireless communication (USB and Bluetooth)
- Power supply by power adapter, chargeable or non- chargeable batteries ●
- Single use microcuvettes (test consumable)
- Labeling: ●
- O Operating Manual
- o Package Insert
- Quick reference Guide o
- o Labels
The microcuvette serves both as a pipette and as a measuring cuvette. No dilution or other preparation of the blood sample is required before filling of the microcuvette. A whole blood sample of approximately 10 uL is drawn into the cavity in the microcuvette by capillary action.
The measurement takes place in the analyzer, which measures the absorbance of whole blood at an Hb/ HbO2 isosbestic point. The measurement is performed directly on the whole blood through measurement of the transmitted and scattered light and using an algorithm for translation into the hemoglobin concentration of the sample.
The HemoCue® Hb 801 System is traceable to the hemiglobincyanide (HiCN) method, the international reference method according to ICSH for the determination of the hemoglobin concentration in blood.
4. Intended use and Indications for Use
Intended Use
The HemoCue® Hb 801 System is intended for the quantitative determination of hemoglobin in capillary or venous whole blood (K2EDTA and Li-Heparin) in point-of-care settings. The HemoCue® Hb 801 System is intended to be used to determine the hemoglobin concentration for adults, adolescents, children, and infants above 1 month old. The HemoCue® Hb 801 System is for professional in vitro diagnostic use only.
Indications for Use Same as intended use.
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5. Substantial Equivalence
| Candidate device | Predicate device | |
|---|---|---|
| Proprietary name: | HemoCue® Hb 801 System | HemoCue® Hb 301 System |
| Common name: | Hemoglobin analyzing system | Hemoglobin analyzing system |
| 510(k) number | / | K061047 |
| Product code | GKR | GKR |
| Classification | Class II | Class II |
| Regulation | 21 CFR 864.5620 | |
| Automated hemoglobin system | 21 CFR 864.5620 | |
| Automated hemoglobin system | ||
| Classification Panel | Hematology | Hematology |
The most important similarities and differences between the HemoCue® Hb 801 System (Candidate Device) and HemoCue® Hb 301 System (Predicate Device) are listed in the table below.
| Characteristic | HemoCue® Hb 801 System
(Candidate device) | HemoCue® Hb 301 System
(Predicate device) |
|---------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analyzer | Image: HemoCue® Hb 801 System Analyzer | Image: HemoCue® Hb 301 System Analyzer |
| Microcuvette | Image: HemoCue® Hb 801 System Microcuvette | Image: HemoCue® Hb 301 System Microcuvette |
| Characteristic | HemoCue® Hb 801 System
(Candidate device) | HemoCue® Hb 301 System
(Predicate device) |
| | Similarities | |
| Intended Use | The HemoCue® Hb 801 System is
intended for the quantitative
determination of hemoglobin in
capillary or venous whole blood
(K2EDTA and Li-Heparin) in point-
of-care settings. The HemoCue® Hb
801 System is intended to be used to
determine the hemoglobin
concentration for adults, adolescents,
children, and infants above 1 month
old. The HemoCue® Hb 801 System
is for professional in vitro diagnostic
use only. | The HemoCue® Hb 301 System is
designed for quantitative point-of-care
whole blood hemoglobin determination
in primary care using a specially
designed analyzer, the HemoCue Hb
301 Analyzer, and specially designed
microcuvettes, the HemoCue Hb 301
Microcuvettes. The HemoCue Hb 301
System is for In Vitro Diagnostic use
only. The HemoCue Hb 301 Analyzer
is only to be used with HemoCue Hb
301 Microcuvettes. |
| Analyte | Hemoglobin | Same |
| Sample preparation
(pre-treatment) | None | Same |
| Sample volume | 10 μL | Same |
| Measuring principle | Spectrophotometric | Same |
| Reagent | No active ingredients | Same |
| Calibration | The system is traceable to the
hemiglobincyanide (HiCN) method,
according to ICSH. The system is
factory calibrated and needs no
further calibration. | Same |
| Quality control | Internal self-test (verifying analyzer
performance) | Same |
| | Differences | |
| Sample type | Capillary or venous whole blood | Capillary, venous or arterial whole
blood |
| Measuring range | 1-25.6g/dL | 0-25.6 g/dL |
| Connectivity | • Wireless Bluetooth Low
Energy (BLE)
• USB | Serial port |
| Microcuvette insertion
technique | "Slot in" | Tray |
| Characteristic | HemoCue® Hb 801 System | HemoCue® Hb 301 System |
| | (Candidate device) | (Predicate device) |
| | Image: HemoCue® Hb 801 System | Image: HemoCue® Hb 301 System |
| User interface | ● Display | ● Display |
| | ● Beeper | ● Beeper |
| | ● Two buttons | ● One button |
| | ● Status LED | |
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8
6. Measuring principle
Spectrophotometric
7. Standard/Guidance Referenced
- CLSI EP05-A3; Evaluation of Precision Performance of Qualitative Measurement Methods; . Approved Guideline - Third Edition.
- CLSI EP06-A; Evaluation of the Linearity of Quantitative Measurement Procedures: A ● Statistical Approach; Approved Guideline.
- CLSI EP07-A2: Interference Testing in Clinical Chemistry: Approved Guideline Second . Edition.
- CLSI EP07- Interference Testing in Clinical Chemistry; Approved Guideline -Third Edition ●
- CLSI EP37; Supplemental Tables for Interference Testing in Clinical Chemistry First Edition ●
- CLSI EP09-A3; Measurement procedure comparison and Bias Estimation Using Patient Samples; Approved Guideline - Third Edition.
- CLSI EP17-A2; Evaluation of Detection Capability for Clinical Laboratory Measurement ● Procedures; Approved Guideline - Second Edition.
- CLSI EP25-A; Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline. ●
- CLSI EP28-A3c; Defining, Establishing, and Verifying Reference Intervals in the Clinical ● Laboratory; Approved Guideline - Third Edition.
9
- . CLSI H15-A3 Reference and Selected Procedures for the Quantitative Determination of Hemoglobin in Blood; Approved Standard - Third Edition.
- IEC 61010-1: 2010 (Third Edition) + AMD1:2016, Safety requirements for electrical equipment for measurement, control and laboratory use - Part 1: General requirements.
- IEC 61010-2-101:2015 (Second Edition), Safety requirements for electrical equipment for ● measurement, control and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment.
- IEC 61326-1:2012 (Second Edition), Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements.
- IEC 61326-2-6:2012 (Second Edition), Electrical equipment for measurement, control and ● laboratory use - EMC requirements - Part 2-6: Particular requirements - In vitro diagnostic medical equipment.
- Electromagnetic Compatibility according to FCC CFR 47 Part 15 ●
- IEC 62304:2006 (First Edition), Medical device software - Software life cycle processes
- ISO 14971:2007 (Second Edition), Medical devices Application of risk management to ● medical devices
8. Performance Characteristics (if/when applicable)
-
- Analytical performance
- a. Precision Whole Blood
Whole blood precision study was conducted with the purpose to verify repeatability, reproducibility, within-laboratory and between lot and site precision of the HemoCue® Hb 801 System by using venous K2EDTA whole blood samples. This study was divided in two different parts, Part 1 a multi-microcuvette lots and Part 2 a multi-site test to evaluate repeatability, within laboratory precision and reproducibility.
Multi-microcuvette study was performed at a single site over 5 operating day. Six hemoglobin levels were analyzed with 5 separate runs testing 5 replicates with three lots of HemoCue® Hb 801 Microcuvette and one HemoCue® Hb 801 Analyzers. Each blood sample was analyzed with 25 replicates per microcuvette lot, providing 75 measurements for each level.
Multi-site study was performed at 3 sites during 5 operating days. Six hemoglobin levels were analyzed with five separate runs testing five replicates at each site using three HemoCue® Hb 801 Analyzers and one lot of HemoCue® Hb 801 Microcuvette. Each blood sample was analyzed with 25 replicates using one analyzer per site, providing 75 measurements for each level.
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| Hb level
(g/dL) | Mean
(g/dL) | SD (g/dL) | CV (%) | SD (g/dL) | CV (%) | SD (g/dL) | CV (%) |
|--------------------|----------------|-----------|--------|-----------|--------|-----------|--------|
| 2.0-3.0 | 2.43 | 0.05 | - | 0.05 | - | 0.05 | - |
| 6.0-7.0 | 6.55 | 0.07 | - | 0.08 | - | 0.08 | - |
| 9.5-10.5 | 9.96 | - | 0.68 | - | 0.71 | - | 1.11 |
| 13.5-14.5 | 14.07 | - | 0.71 | - | 0.82 | - | 1.16 |
| 16.5-17.0 | 16.87 | - | 0.60 | - | 0.73 | - | 0.95 |
| 23.0-24.0 | 23.39 | - | 0.67 | - | 0.77 | - | 0.97 |
all precision based on all HemoCue® Hh 801 microcuvette lots
Table 2: Overall precision based on all sites
| Hb level
(g/dL) | Mean
(g/dL) | Repeatability | | Within Lab Precision | | Reproducibility | |
|--------------------|----------------|---------------|--------|----------------------|--------|-----------------|--------|
| | | SD (g/dL) | CV (%) | SD (g/dL) | CV (%) | SD (g/dL) | CV (%) |
| 2.0-3.0 | 2.30 | 0.03 | - | 0.04 | - | 0.05 | - |
| 6.0-7.0 | 6.55 | 0.07 | - | 0.07 | - | 0.08 | - |
| 9.5-10.5 | 10.24 | - | 1.04 | - | 1.17 | - | 1.63 |
| 13.5-14.5 | 13.91 | - | 0.71 | - | 0.75 | - | 1.00 |
| 16.5-17.0 | 16.75 | - | 0.52 | - | 0.63 | - | 0.66 |
| 23.0-24.0 | 23.35 | - | 0.74 | - | 0.74 | - | 0.89 |
b. Precision - Quality Control Material
A precision study was conducted at three sites over 20 operating days using three HemoCue® Hb 801 Microcuvette lots (one lot per site), three HemoCue® Hb 801 Analyzers (one analyzer per site), and 1 lot of control material (level 1= low, level 2= medium, level 3= high). Each control set was run in duplicate twice daily for 20 days, by 10 operators (minimum 2 operators per site). A total of 240 measurements (80 per level) were generated at each site. SD and CV calculated for repeatability, between-run, between-day and within laboratory precision for each level were within the defined acceptance criteria. Also, SD and CV calculated for repeatability, within-laboratory precision and reproducibility combined for all sites per level were within the defined acceptance criteria.
| Table 3: Overall precision, based on all sites, all microcuvette lots, all operators and all days per level | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Control
Level | Mean
Value
(g/dL) | Number
of
results | Repeatability | | Within Lab/site
Precision | | Reproducibility | |
|------------------|-------------------------|-------------------------|---------------|--------|------------------------------|--------|-----------------|--------|
| | | | SD (g/dL) | CV (%) | SD (g/dL) | CV (%) | SD (g/dL) | CV (%) |
| Low | 6.34 | 240 | 0.05 | 0.7 | 0.04 | 0.7 | 0.06 | 0.9 |
| Medium | 11.50 | 240 | 0.05 | 0.4 | 0.05 | 0.5 | 0.06 | 0.5 |
| High | 15.36 | 240 | 0.15 | 1.0 | 0.16 | 1.0 | 0.17 | 1.1 |
c. Linearity
A linearity study was conducted using hemoglobin concentration prepared from a single, venous whole blood sample. A total of 9 hemoglobin concentration (0.50, 3.78, 7.05, 10.33, 13.60, 16.88, 20.15, 23.43, 26.70 g/dL) spanning the claimed measuring range of the HemoCue® Hb 801 Analyzer (1.0-25.6 g/dL) were tested with 15 replicates and analyzed using three HemoCue® Hb 801 Analyzers (5 replicates/analyzer) and one lot of HemoCue® Hb 801 Microcuvette. The statistical analysis was performed separately for each analyzer using a polynomial regression analysis using first, second and third order fits. Statistical testing was used to determine the polynomial model with the best fit by examining the standard error of the regression, Syx.
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The HemoCue® Hb 801 System is linear in the range 1.0-25.6 g/dL with fulfilled acceptance criteria for the non-linear error.
d. Shelf -life
HemoCue® Hb 801 Microcuvette shelf-life was determined by using 3 lots of HemoCue® Hb 801 Microcuvette. At every analysis run, the microcuvettes were tested with 3 venous K2EDTA whole blood samples from 3 different subjects at each Hb level (a total of 9 fresh blood samples per analysis run). The shelf life of the HemoCue® Hb 801 Microcuvette is determined to 6 months (at time of premarket notification, will be extended)
e. Detection limit
Limit of Blank (LoB)
To determine Limit of Blank (LoB), plasma samples were obtained from four individual whole blood samples. The study was conducted with 3 HemoCue® Hb 801 Analyzers and 2 lots of HemoCue® Hb 801 Microcuvette over 4 operating days. One sample was analyzed each day at 3 different runs separated by at least 2 hours between each run. Two replicates/analyzer were analyzed at each run, in total 72 replicates/microcuvette lot. The data from both microcuvette lots were combined and the Anderson Darling normality test showed a non-normal distribution of the measuring results. The rank position was calculated according to the non-parametric option, using a-error 0.05 (yields p =0.95). 72 measurements resulted in a rank position of 68.9. LoB for the HemoCue® Hb 801 System was determined to be 0.26 g/dL.
Limit of Detection (LoD)
To determine Limit of Detection (LoB), four K2EDTA whole blood samples were collected from different subjects. Four independent samples were prepared and the Hb-levels were within 1-5 times the LoB value and distributed within the range 0.46 - 1.0 g/dL. The study was conducted over 4 operating days using 3 HemoCue® Hb 801 Analyzers and 2 lots of HemoCue® Hb 801 Microcuvette. Four samples were analyzed where one sample was analyzed each day at 3 different runs with at least 2 hours between each run and with 2 replicates/analyzer and run, totally 72 replicates/microcuvette lot. The data has been evaluated and showed to have equal variance and LoD was established with a ß-error at 0.05. LoD for the HemoCue® Hb 801 System was determined to be 0.3 g/dL.
Limit of Quantification (LoQ)
To determine Limit of Quantification (LoQ), four K2EDTA whole blood samples were collected from different subjects. Four independent samples were prepared and the Hb-levels of the samples were slightly above LoD, within the range 0.40-0.52 g/dL. The study was conducted with 3 HemoCue® Hb 801 Analyzers and 2 lots of HemoCue® Hb 801 Microcuvette over 4 operating days. Samples were analyzed within the interval of LoD+0.4 g/L, where one sample was analyzed each day at 3 different runs with at least 2 hours between each run and with 3 replicates /analyzer and run, totally 108 replicates /microcuvette lot. Total Error for each sample was calculated by using the RMS-model. The calculated TE for each microcuvette lot was reviewed against the
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defined goal for TE 8≤ 0.5 g/dL. LoQ for the HemoCue® Hb 801 System was determined to be 0.5 g/dL.
- f. Analytical specificity
The purpose of the interference studies was to evaluate the effect of potential interferents on the HemoCue® Hb 801 System.
The study was performed by adjusting Hb-levels of the K2EDTA whole blood samples collected. Each sample was divided into a reference group and a test group containing potential interferent at the test concentration listed below.
For potential interferences from leucocytes and platelets, and certain patient conditions (Sickle cells, Polycythemia vera, Thalassemia/hypochromia and Anemia) the interference was evaluated by using a comparative procedure between the HemoCue® Hb 801 System and ICSH as a reference method.
The following substances have been tested at hemoglobin concentrations 10±0.5 and 20±1.0 g/dL. No interference was found at following concentrations of the substances tested.
| Substance | Test concentration | Unit |
|---|---|---|
| Acetaminophen | 1324 | µmol/L |
| Ascorbic acid | 342 | µmol/L |
| Creatinine | 442 | µmol/L |
| HbCO | 10 | % |
| HbO2 | ≤ 50 | % |
| Hemolysis | 10 | g/L |
| Ibuprofen | 2425 | µmol/L |
| MetHb* | 25 | % |
| Platelets | 2000 | x 109/L |
| Total protein | 15 | g/dL |
| Salicylic acid | 4.34 | mmol/L |
| Simvastatin | 49 | µmol/L |
| Tetracycline | 34 | µmol/L |
| Triglycerides | 1500 | mg/dL |
| Urea | 42.9 | mmol/L |
| Uric acid | 1.4 | mmol/L |
| Warfarin | 32.5 | µmol/L |
*Multiple concentrations of MetHb up to 25% were tested and did not interfere with hemoglobin measurement at Hb-level 10±0..
Normal blood pH and above, up to 8, at Hb level 10±0.5 or 20±1.0 g/dL do not interfere with the system.
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| Substance | Concentration (unit) | Hb concentration (g/dL) | Result |
|---|---|---|---|
| Conjugated | |||
| bilirubin | >23 (mg/dL) | 10 | Interfering* |
| Conjugated | |||
| bilirubin | Up to 40 (mg/dL) | 20 | Non-interfering |
| Unconjugated | |||
| bilirubin | >12 (mg/dL) | 10 | Interfering* |
| Unconjugated | |||
| bilirubin | >23 (mg/dL) | 20 | Interfering* |
| Intralipid | >214 (mg/dL) | 10 | Interfering* |
| Intralipid | >483 (mg/dL) | 20 | Interfering* |
| Leucocytes | >260 x 109/L | 6.8 – 14.7 | Interfering* |
The following substances have been tested to determine the interfering concentration.
- May give elevated results in higher substance concentrations.
- g. Within Measurement Equivalence Tests: Anticoagulants
The purpose of this study was to demonstrate the equivalence between the anticoagulants K2EDTA and Li-Heparin on the HemoCue® Hb 801 System. The study was conducted at two sites, over 5 operating days at each site, using one HemoCue® Hb 801 Analyzer and one lot of HemoCue® Hb 801 Microcuvettes. Each out of 120 subjects provided one fresh venous K2EDTA and one fresh venous Li-Heparin whole blood samples. Additional samples were collected from 11 subjects to adjust Hb value to high and low Hb values. The regression analysis was performed by using replicate 1 from the sample in the Li-Heparin tube vs. replicate 1 from the sample from the K2EDTA tube.
Both the K2EDTA and Lithium Heparin samples fulfils the acceptance criteria regarding the correlation and bias between the two anticoagulants used on the HemoCue® 801 System.
-
h. Within Measurement Equivalence Tests: Capillary vs. Venous Sample
The purpose of this study was to verify the equivalency of venous and capillary whole blood samples on the HemoCue® Hb 801 System. Capillary and venous whole blood samples were collected from 40 subjects, within an as wide range as possible. Additional data points from 212 subjects were taken from the method comparison study. The regression analysis was performed by using replicate from the venous sample vs. replicate from the capillary sample from the same subject. The venous K2EDTA blood sample was collected directly after collection of the capillary sample. Both the venous and capillary samples were within the defined acceptance criteria and showed equivalency when used on the HemoCue® Hb 801 System. -
i. Assay cut-off
N/A
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-
- Method Comparison Study
- a. Method comparison with predicate device
Method comparison studies were performed to evaluate the accuracy of the HemoCue® Hb 801 System in the hands of intended users in point-of-care facilities when testing capillary and/or venous blood from individuals 1 month of age and older. The studies were performed at five primary care settings in the US over 73 operating days.
The study included a total of 264 venous and 233 capillary whole blood samples. Both venous and capillary whole blood samples were tested at each site using the HemoCue® Hb 801 System and the predicate device, HemoCue® Hb 301 System (comparative method, in duplicate). The studies were performed on six HemoCue® Hb 801 Analyzers and four lots of HemoCue® Hb 801 Microcuvette by 13 operators. 6 % of the total number of samples (28/497 samples) were adjusted (contrived) in order to cover the lower and upper ends of the HemoCue® Hb 801 System's Analytical Measuring Range (AMR).
The results for all venous samples respectively all capillary samples are summarized in the table below. Linear regression analysis demonstrated comparable performance between the HemoCue® Hb 801 System and HemoCue® Hb 301 System.
| Sample type | Total
n = | Contrived
n = | Slope
(95% CI) | Intercept
(95% CI) | r |
|------------------|--------------|------------------|------------------------|---------------------------|------|
| K2EDTA
Venous | 264 | 28 | 1.00
(0.99 to 1.01) | -0.14
(-0.26 to -0.03) | 1.00 |
| Capillary | 233 | NA | 1.07
(1.02 to 1.12) | -0.91
(-1.54 to -0.28) | 0.96 |
Table 4: Method comparison study overall summary, all sites combined
In addition, 71 pediatric samples were tested at one European clinical laboratory site over 7 operating days. Each blood sample was analyzed with 2 replicates on the HemoCue® Hb 801 System, with 2 replicates on the predicate device HemoCue® Hb 301 System, and with 3 replicates with the reference method ICSH.
Regression analysis demonstrated comparable performance between the HemoCue® Hb 801 System and ICSH and between the HemoCue® Hb 801 System and HemoCue® Hb 301 System.
In the linear regression analysis of the relationship between HemoCue® Hb 801 System and reference method ICSH, have a slope 0.95 and a correlation coefficient (r) 0.99.
In the linear regression analysis of the relationship between HemoCue® Hb 801 System and the predicate device HemoCue® Hb 301 System, have a slope 0.97 and a correlation coefficient (t) 0.99.
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Both the venous and capillary samples were within the defined acceptance criteria. HemoCue® Hb 801 System provides a quantitative Hb measurement in both venous and capillary whole blood samples for adults and children above 1 month old and support use at point-of-care settings.
b. Matrix comparison
For Within Measurement Equivalence Tests on Anticoagulants and Capillary vs. Venous sample, refer to "Performance Characteristics" Section above.
3. Clinical studies
- Clinical Sensitivity a. N/A
- b. Clinical specificity N/A
- Other clinical supportive data (when a. and b. are not applicable): C. N/A
4. Clinical cut-off
N/A
5. Reference range
Reference ranges were verified by testing whole blood specimens collected and tested at 5 point-ofcare locations in the US on the HemoCue® Hb 801 System. The values of the collected samples have been compared against the reference ranges to assess if the obtained values fall within the expected pediatric and adult reference intervals1.2.
The study results verified that the reference ranges data on the HemoCue® Hb 801 System for the subgroups fall within the defined reference ranges below.
| Subject group | Age | Hb, g/dL |
|---|---|---|
| Infant | >1 month -2 years | 9.4 - 14.1 |
| Child | >2 - 12 years | 11.0 - 15.5 |
| Adolescent | >12 - 21 years | 10.9 - 15.1 |
| Adult Male | >21 years | 13.0-17.0 |
| Adult Female | >21 years | 12.0-15.0 |
Table 5: Defined reference range
1 Dacie and Lewis Practical Haematology, Elsevier Limited, 11th Edition, 2011 and references herein 2 Soldin, S. J. Pediatric Reference Intervals, AACC Press; 7th edition, 2011
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6. Instrument name
HemoCue® Hb 801 System
7. System Description
- a. Mode of operation
The HemoCue® Hb 801 System provides a direct reading of the hemoglobin concentration in a sample using specially designed, single use microcuvette and an analyzer.
The microcuvette serves both as a pipette and as a measuring cuvette. No dilution or other preparation of the blood sample is required before filling of the microcuvette. A whole blood sample of approximately 10 uL is drawn into the cavity in the microcuvette by capillary action.
The measurement takes place in the analyzer, which measures the absorbance of whole blood at an Hb/ HbO2 isosbestic point. The measurement is performed directly on the whole blood through measurement of the transmitted and scattered light and using an algorithm for translation into the hemoglobin concentration of the sample.
The HemoCue® Hb 801 System is be traceable to the hemiglobincyanide (HiCN) method, the international reference method according to ICSH for the determination of the hemoglobin concentration in blood.
-
b. Software
Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." The software for this device is "moderate" level of concern. -
c. Specimen Identification
There is no specimen identification function for the HemoCue® Hb 801 System. -
d. Specimen Sampling and Handling
A whole blood sample of approximately 10 uL is drawn into the cavity in the HemoCue® Hb 801 Microcuvette by capillary action. To perform a hemoglobin reading, a filled microcuvette is inserted into the microcuvette holder in the HemoCue® Hb 801 Analyzer. -
e. Calibration
The HemoCue® Hb 801 System is factory calibrated and needs no further calibration.
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f. Quality Controls
The HemoCue® Hb 801 Analyzer has an internal quality control, a self-test. It automatically verifies that the optronic unit of the analyzer is working properly every time the analyzer is turned on, when the microcuvette holder is put back into place after removal, and every hour when in use.
If an external quality control is required by local or other regulations, commercially available controls recommended by HemoCue should be used.
8. Other Supportive Instrument Performance Characteristics Data Not Covered In the "Performance Characteristics" Section above
Cleaning and Disinfection Study
A cleaning and disinfection study was conducted to validate virucidal efficacy using the selected disinfectant with the recommended disinfection protocol. Super Sani-Cloth®Germicidal Disposable Wipe (EPA Registration No. 9480-4), a ready to use pre-saturated towelette, demonstrated complete inactivation of Duck Hepatitis B virus (surrogate for Human Hepatitis B virus) for all tested materials, following two-minutes exposure at room temperature.
A robustness study was performed to demonstrate that the HemoCue® Hb 801 System is robust to multiple cleaning and disinfection cycles by using Super Sani-Cloth® Germicidal Disposable Wipe.
9. Proposed Labeling
The labeling is sufficient and it satisfies the requirements of 21CFR Part 809.10.
10. Conclusion
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.