(273 days)
The BC-3600 auto hematology analyzer is a quantitative, automated hematology analyzer for in vitro diagnostic use in clinical laboratories. The BC-3600 auto hematology analyzer provide complete blood count (WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV) and leukocyte 3-Part differential (Lymph#, Mid#, Gran#, Lymph%, Mid%, Gran%) for whole blood specimens, collected in a salt of EDTA [dipotassium (K2) or tripotassium (K3)] obtained by venipuncture or fingerstick. The purpose of the BC-3600 Auto Hematology Analyzer is to identify the normal human patient, with normal system-generated parameters, from patients whose results require additional studies.
The BC-3600Auto Hematology Analyzer is a quantitative, automated hematology analyzer and leukocyte differential counter for In Vitro Diagnostic Use in clinical laboratories. It is only to be used by trained medical professionals to identify the normal patient, with all normal system-generated parameters, and to flag or identify patient results that require additional studies. The analyzer provides analysis results of 16 parameters of human blood and three histograms.
The BC-3600 Auto Hematology Analyzer system consists of:
- The analyzer (BC-3600)
- Reagents (M-30D DILUENT, M-30CFL LYSE, M-30R RINSE, PROBE CLEANSER)
- Controls (BC-3D Control (High, Normal, Low levels))
- Calibrator (SC-CAL PLUS Calibrator)
The analyzer provides analysis results of 16 parameters (WBC, Lymph#, Mid#, Gran#, Lymph%, Mid%, Gran%, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV) of human blood and three histograms (WBC Histogram, RBC Histogram, PLT Histogram).
The provided text describes the Mindray BC-3600 Auto Hematology Analyzer and its substantial equivalence to the predicate device, BC-3200 Hematology Analyzer.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a table of "acceptance criteria" against which the device performance is directly compared column-by-column. Instead, it describes performance characteristics and states that the device "met the pre-defined specification of the difference limits" or "passed specifications." We can infer the acceptance criteria from the context of these statements and the reported performance.
For method comparison against the predicate device (BC-3200), the acceptance criteria are implicitly defined by the parameters r (correlation coefficient), slope (95% CI), and intercept (95% CI) and the statement that biases met pre-defined limits. For flagging ability, the percentages for sensitivity, specificity, and efficiency serve as the reported performance, with implicit acceptance criteria for these values. For carryover, an explicit acceptance criterion is given.
| Performance Characteristic | Acceptance Criteria (Implicit/Explicit) | Reported Device Performance |
|---|---|---|
| Method Comparison (vs. Predicate BC-3200) | (See Table 1 and accompanying text) | |
| Correlation Coefficient (r) | High correlation (e.g., typically >0.90 to 0.95 for quantitative assays) and slope/intercept within acceptable ranges indicating comparable measurements. | WBC: 0.999Lymph#: 0.985Mid#: 0.873Gran#: 0.998Lymph%: 0.982Mid%: 0.677Gran%: 0.985RBC: 0.997HGB: 0.998HCT: 0.997MCV: 0.994MCH: 0.991MCHC: 0.915RDW: 0.901PLT: 0.992MPV: 0.865Slopes and intercepts with 95% CI reported. Biases "met the pre-defined specification of the difference limits." |
| WBC Flagging Ability (vs. Manual Differential) | Implicitly, clinically acceptable levels of sensitivity, specificity, and efficiency. | Sensitivity: 73.6%Specificity: 76.5%Efficiency: 75.9% |
| Precision/Reproducibility | Coefficients of variation (CV%) and standard deviations (SD) for within-run, between-run, between-day, and within-device (and between-device for combined data) met specifications. | "The reproducibility results in each site met the specifications.""All data in each site passed specifications." |
| Linearity Range (R2) | Coefficient of determination (R2) > 0.95 and parameters recovering within bias limits. | "data fitting a linear regression line with a coefficient of determination (R2) of >0.95 and the parameters measured recovering within the bias limits for each parameters based on CLSI EP06-A." |
| Carryover (WBC, RBC, HGB) | ≤ 0.5% | "results were within specifications (≤ 0.5%)" |
| Carryover (PLT) | < 1.0% | "results were within specifications (< 1.0%)" |
| Sample Stability | Performance results met acceptance limits. | "analyzer performance results met the acceptance limits according to CLSI EP25-A." Specifically, whole blood stable for 24 hours (refrigerated) / 12 hours (room temp, most parameters), 8 hours (differential parameters, room temp). Predilute stable for 30 minutes (room temp). |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison and WBC Flagging Ability:
- Sample Size: 1222 K2EDTA whole blood samples.
- Data Provenance: Three actual user sites, two in China and one in the U.S. Patients aged 1 day to 100 years, with 547 females, 672 males, and 3 unknown. Retrospective/prospective not explicitly stated, but "Patient's samples covered the normal and most abnormal conditions" suggests selection, possibly from archives or collected for the study.
- Precision/Reproducibility: Not explicitly stated as a fixed test set size for patient samples, but control materials were run in duplicate twice a day for 20 days at three clinical sites. For within-run precision, ten replicates of whole blood samples were used around medical decision levels and analytical measuring range limits at three clinical sites.
- Linearity Range: Not explicitly stated as a fixed test set size, but "7 subsequent dilutions" were prepared and "three (3) from each of the 7 dilutions" were measured.
- Comparison of Whole Blood Mode and Predilute Mode Sample:
- Sample Size: 61 pairs of samples.
- Data Provenance: K2EDTA collection tube, not specified if US or China.
- Comparison of Venipuncture and Fingerstick Sample:
- Sample Size: 52 paired specimens.
- Data Provenance: Collected from donors (not specified where, but tested at the U.S. site).
- Comparison of K2EDTA and K3EDTA Anticoagulants Samples:
- Sample Size: 60 paired fresh whole blood samples.
- Data Provenance: Not specified where, but tested at an actual user site in the U.S.
- Sample Stability:
- Whole Blood: 35 normal and abnormal samples collected at Finlay Laboratory (U.S. site).
- Predilute: 25 normal and abnormal samples collected at NSH site (location not specified, likely one of the clinical sites mentioned earlier).
- Reference Interval:
- Sample Size: 255 donors (124 adult male, 131 adult female).
- Data Provenance: Not specified, but adult donors aged 19-85.
- Determination of LoB, LoD, LoQ:
- Sample Size: 5 blank samples and 5 low-level samples, tested 12 times (blank) or 5 times (low-level).
- Data Provenance: One clinical laboratory in China.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Method Comparison and WBC Flagging Ability:
- Number of Experts: Not explicitly stated. The text mentions "A 400 cell WBC differential was performed on two smears per CLSI H20-A2." This typically implies trained laboratory professionals, but the exact number and qualifications (e.g., years of experience, specific certifications) are not provided. CLSI H20-A2 (Reference Leukocyte (WBC) Differential Count (Proportional) and Evaluation of Instrumental Methods) guides this process, which requires expert review.
4. Adjudication Method for the Test Set
- Method Comparison and WBC Flagging Ability: The text states "A 400 cell WBC differential was performed on two smears per CLSI H20-A2." This standard often outlines procedures for resolving discrepancies, but the specific adjudication method (e.g., 2+1, 3+1) is not detailed in the provided summary. It implies expert review for ground truth, but not a specific reader adjudication process for the study.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study focusing on the improvement of human readers with vs. without AI assistance was not performed. This device is an automated hematology analyzer, not an AI-assisted diagnostic tool for human interpretation of images. The comparison was primarily between the new device and the predicate device, and between the device's flagging ability and a manual differential (human expert determination).
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, the performance data presented (e.g., method comparison, WBC flagging ability, precision, linearity, carryover) represents the standalone performance of the BC-3600 Auto Hematology Analyzer. The device is designed to be an automated analyzer providing quantitative results.
7. The Type of Ground Truth Used
- Method Comparison (vs. Predicate): The ground truth for this comparison was the results obtained from the predicate device (BC-3200).
- WBC Flagging Ability: The ground truth for this was established by manual differential counts performed by experts on peripheral blood smears, following CLSI H20-A2 guidelines.
- Precision/Reproducibility: Used commercial control materials (BC-3D control Low, Normal and High).
- Linearity Range: Used dilutions prepared from fresh whole blood and commercial high-value analogs for WBC and PLT.
- Comparisons (Modes, Samples, Anticoagulants): Used the BC-3600 results in different configurations/conditions to show equivalence.
- Sample Stability: Used the BC-3600 results at different time points compared against initial readings.
- Reference Interval: Determined by testing samples from 255 healthy donors.
- LoB, LoD, LoQ: Established using blank samples (diluent) and low-level samples created by adding whole blood to diluent.
8. The Sample Size for the Training Set
- The document describes validation and verification studies for a medical device submitted for 510(k) clearance, not the development or training of an AI algorithm. Therefore, there is no mention of a training set sample size as it pertains to AI/machine learning. The studies described are for demonstrating the performance of the final device against established standards and predicates. This device uses the "Coulter principle of Impedance method" and "Colorimetric method," classical laboratory techniques, not explicitly an AI/ML algorithm that would require a "training set."
9. How the Ground Truth for the Training Set Was Established
- As stated above, this document does not describe the development or training of an AI algorithm, but rather the validation of an automated hematology analyzer based on traditional principles. Therefore, the concept of "ground truth for the training set" does not apply in this context.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
August 21, 2015
Mindray Bio-medical Electronics Co., LTD c/o Jinjie Hu, Ph.D. Senior Consultant Biologics Consulting Group, Inc. 400 N. Washington Street. Suite 100 Alexandria, VA 22314
Re: K143348
Trade/Device Name: BC-3600 Auto Hematology Analyzer Regulation Number: 21 CFR 864.5220 Regulation Name: Automated Differential Cell Counter Regulatory Class: Class II Product Code: GKZ Dated: August 10, 2015 Received: August 14, 2015
Dear Dr. Hu:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21
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Page 2 - Dr. Jinjie Hu
CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Leonthena R. Carrington -S
Leonthena R. Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name BC-3600 Auto Hematology Analyzer
Indications for Use (Describe)
The BC-3600 auto hematology analyzer is a quantitative, automated hematology analyzer for in vitro diagnostic use in clinical laboratories. The BC-3600 auto hematology analyzer provide complete blood count (WBC, RBC, HCT, MCV, MCH, MCHC, RDW, PLT, MPV) and leukocyte 3-Part differential (Lymph#, Mid%, Gran%) for whole blood specimens, collected in a salt of EDTA [dipotassium (K3)] obtained by venipuncture or fingerstick. The purpose of the BC-3600 Auto Hematology Analyzer is to identify the normal human patient, with normal system-generated parameters, from patients whose results require additional studies.
X Prescription Use (Part 21 CFR 801 Subpart D)
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Mindray Bio-medical electronics co., LTD
BC-3600 Auto Hematology Analyzer
510(k) Premarket Notification
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1. 510(K) SUMMARY
In accordance with 21 CFR 807.87(h) and (21 CFR 807.92) the 510(k) Summary for the BC-3600 Auto Hematology Analyzer is provided below.
| Device Common Name: | Auto Hematology Analyzer |
|---|---|
| Device Proprietary Name: | BC-3600 Auto Hematology Analyzer |
| Submitter: | Mindray Bio-medical electronics co., LTDMindray Building, Keji 12th Road South, High-techIndustrial Park, Nanshan,Shenzhen, Guangdong 518057, P.R. China |
| Contact: | Jinjie Hu Ph.D.400 N. Washington StreetSuite 100Alexandria, VA 22314Tel: 301-814-4985Email: jhu@bcg-usa.com |
| Date Prepared: | November 14, 2014 |
| Classification Regulation: | 21 CFR 864.5220, Class II |
| Panel: | Hematology |
| Product Code: | GKZ |
Predicate Device:
BC-3200 Hematology Analyzer (K093394) BC-3200 AUTO HEMATOLOGY ANALYZER, M-30D DILUENT, M-30R RINSE, M-30CFL LYSE, M-30E E-Z CLEANSER, M-30P PROBE CLEANSER, BC-3D, SC-CAL PLUS. SHENZHEN MINDRAY BIO-MEDICAL ELECTRONICS CO., LTD
Indication for Use:
The BC-3600 auto hematology analyzer is a quantitative, automated hematology analyzer for in vitro diagnostic use in clinical laboratories. The BC-3600 auto hematology analyzer provide complete blood count (WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV) and leukocyte 3-Part differential (Lymph#, Mid#, Gran#, Lymph%, Mid%, Gran%) for whole blood specimens, collected in a salt of EDTA [dipotassium (K2) or tripotassium (K3)] obtained by venipuncture or fingerstick. The purpose of the BC-3600 Auto Hematology Analyzer is to identify the normal human patient, with normal system-generated parameters, from patients whose results require additional studies.
Device Description
The BC-3600Auto Hematology Analyzer is a quantitative, automated hematology analyzer and leukocyte differential counter for In Vitro Diagnostic Use in clinical laboratories. It is only to be used by trained medical professionals to identify the normal
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patient, with all normal system-generated parameters, and to flag or identify patient results that require additional studies. The analyzer provides analysis results of 16 parameters of human blood and three histograms.
The BC-3600 Auto Hematology Analyzer system consists of:
- The analyzer (BC-3600) ●
- . Reagents
- M-30D DILUENT ।
- M-30CFL LYSE -
- M-30R RINSE
- PROBE CLEANSER
- . Controls
- BC-3D Control (High, Normal, Low levels)
- . Calibrator
- SC-CAL PLUS Calibrator
The analyzer provides analysis results of 16 parameters (listed below) of human blood and three histograms. The following list provides the abbreviations for all measurands:
| Parameter | Abbreviation |
|---|---|
| White Blood Cell or leukocyte | WBC |
| Lymphocyte | Lymph# |
| Mid-sized cell | Mid# |
| Granulocyte | Gran# |
| Lymphocyte percentage | Lymph% |
| Mid-sized cell percentage | Mid% |
| Granulocyte percentage | Gran% |
| Red Blood Cell or erythrocyte | RBC |
| Hemoglobin Concentration | HGB |
| Hematocrit | HCT |
| Mean Corpuscular (erythrocyte) Volume | MCV |
| Mean Cell (erythrocyte) Hemoglobin | MCH |
| Mean Cell (erythrocyte) Hemoglobin Concentration | MCHC |
| Red Blood Cell (erythrocyte) Distribution Width | RDW |
| Platelet | PLT |
| Mean Platelet Volume | MPV |
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White Blood Cell Histogram Red Blood Cell Histogram Platelet Histogram
WBC Histogram RBC Histogram PLT Histogram
Principle of Operation
WBCs are counted and sized by the impedance method. This method is based on the measurement of changes in electrical resistance produced by a particle, which in this case is a blood cell suspended in a conductive diluent as it passes through an aperture of known dimensions. HGB is determined by the colorimetric method. RBCs and PLTs are counted by the impedance method also. In addition, volumetric metering is used. An accurate cell count cannot be obtained unless the precise volume of diluted sample that passes through the aperture during the count cycle is known. The analyzer uses a volumetric metering unit to control the count cycle and to ensure that a precise volume of sample is analyzed for the measurement.
Modes of Operation
The BC-3600 operates in a closed vial
Specimen identification
Specimen identification input is manual (by operator) or by barcode reader (optional).
Specimen sampling and handling
Samples are manually mixed and loaded into a sample compartment one at a time. The BC-3600 processes anti-coagulated whole blood collected in a K2EDTA or K3EDTA on two testing modes: whole blood analysis mode and predilute analysis mode.
Reagents. Calibrators and Controls
Reagents:
- . M-30D DILUENT
- M-30R RINSE
- M-30CFL LYSE ●
- PROBE CLEANSER .
Controls: BC-3D
Three levels of Controls with low, normal and high levels are provided. These Controls are exactly same as the Controls cleared in the predicate device BC-3200 analyzer. It is recommended to perform the quality control check using these controls at intervals established by the laboratory procedures and local or national regulations.
Calibrators: SC-CAL PLUS
Calibration and verification of Calibration are performed with the previously cleared Calibrator SC-CAL PLUS in the predicate device BC-3200 analyzer. The calibration and
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quality control should be performed according to the instruction for the Calibrator and to laboratory procedures and local or national regulations.
Software
The software is used to operate the system which features sample management, sample processing, data acquisition, data processing, result management, patient data management, and instrument management. The system is comprised of the BC-3600 analyzer with touch screen.
The BC-3600 Auto Hematology Analyzer contains moderate risk level software which has been fully verified and validated and documentation in accordance with FDA Guidance "Guidance for the Content of Premarket Submission for Software Contained in Medical Devices: May 11, 2005" has been provided in this submission.
| FDAGuidance | Class II Special Controls Guidance Document: PremarketNotifications for Automated Differential Cell Counters for Immatureor Abnormal Blood Cells; Final Guidance for Industry and FDA | 2001 |
|---|---|---|
| H26-A2 | Validation, Verification, and Quality Assurance of AutomatedHematology Analyzers; Proposed Standard - Second Edition | 2010 |
| EP6-A | Evaluation of the Linearity of Quantitative MeasurementProcedures: A Statistical Approach; Approved Guideline | 2003 |
| H20-A2 | Reference Leukocyte (WBC) Differential Count (Proportional) andEvaluation of Instrumental Methods; Approved Standard - SecondEdition | 2007 |
| EP09-A3 | Measurement Procedure Comparison and Bias Estimation UsingPatient Samples; Approved Guideline - Third Edition | 2014 |
| EP17-A | Protocols for Determination of Limits of Detection and Limits ofQuantitation; Approved Guideline | 2009 |
| EP5-A2 | Evaluation of Precision Performance of Quantitative MeasurementMethods; Approved Guideline-Second Edition | 2005 |
| C28-A3 | Defining, Establishing, and Verifying Reference Intervals in theClinical Laboratory; Approved Guideline- Third Edition | 2008 |
Special Control and Guidance Document Referenced
Performance Characteristics
Method comparison
A total of 1222 K2EDTA whole blood samples were studied at three actual user sites, two in China and one in the US. Patients participated the study with age range from 1 day after birth to 100 years old, and with 547 females, 672 males and 3 samples with unknown age and gender. Patient's samples covered the normal and most abnormal
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conditions for all parameters. For each whole blood sample, three manual wedge smears were prepared and stained with Wright-Giemsa stain. A 400 cell WBC differential was performed on two smears per CLSI H20-A2. All samples were testing on whole blood mode in parallel with BC-3600 analyzer and the predicate device. An estimation of the bias was determined for each parameter according to EP09-A3. The result demonstrated the BC-3600 analyzer met the pre-defined specification of the difference limits. Whole blood accuracy and regression vs predicate and the flagging ability of BC-3600 vs Manual differential comparison was performed. Table 1 shows that the combined results from three (3) sites are comparable to the predicate device.
| Parameters | Result Range | r | slope(95%CI) | intercept(95%CI) | Mean | |
|---|---|---|---|---|---|---|
| Predicate | Test | |||||
| WBC(x 10³/uL) | 0.15 to 103.1 | 0.999 | 0.990(0.988 to 0.992) | 0.1861(0.152 to 0.22) | 11.29 | 11.36 |
| Lymph#(x 10³/uL) | 0.1 ~ 12.45 | 0.985 | 1.0665(1.057~1.076) | -0.155(-0.176~-0.134) | 2.16 | 2.15 |
| Mid#(x 10³/uL) | 0.05~2.75 | 0.873 | 1.101(0.964~1.237) | -0.06537(-0.12974~-0.001) | 0.60 | 0.60 |
| Gran#(x 10³/uL) | 0.1 ~ 47.65 | 0.998 | 1.0674(1.064~1.071) | -0.2177(-0.242~-0.193) | 5.96 | 6.15 |
| Lymph%(%) | 3.55~69.3 | 0.982 | 1.098(1.088~1.108) | -3.2854(-3.615~-2.956) | 30.67 | 30.39 |
| Mid%(%) | 2.25 ~ 14.85 | 0.677 | 0.577(0.544~0.610) | 3.2976(3.031~3.564) | 8.28 | 8.07 |
| Gran%(%) | 23 ~ 92.95 | 0.985 | 1.0462(1.037~1.055) | -1.9542(-2.524 ~ - 1.385) | 62.48 | 63.41 |
| RBC(x 10⁶/uL) | 1.04~7.57 | 0.997 | 1.0098(1.007~1.013) | -0.0296(-0.043 ~ -0.016) | 4.25 | 4.26 |
| HGB(g/dL) | 3.05 ~ 24.55 | 0.998 | 1.0055(1.003~1.008) | -0.1434(-0.178 ~ -0.109) | 12.45 | 12.37 |
| HCT(%) | 9.6~73.75 | 0.997 | 0.9829(0.98~0.986) | 0.8568(0.732~0.982) | 38.03 | 38.23 |
| MCV(fL) | 50.7~124 | 0.994 | 1.0132(1.009~1.018) | -0.875(-1.27~-0.48) | 90.46 | 90.77 |
| MCH(pg) | 15.3 ~ 44.25 | 0.991 | 1.0087(1.003~1.014) | -0.4767(-0.641~ -0.312) | 29.58 | 29.36 |
| MCHC(d/fL) | 25.15~47.65 | 0.915 | 0.943(0.926~0.959) | 1.4625(0.922~2.003) | 32.69 | 32.28 |
| RDW(%) | 11 ~ 20.7 | 0.901 | 1.1667(1.1395~1.1892) | -2.4167(-2.7514~-2.0523) | 14.28 | 14.23 |
| PLT(x 10³/uL) | 12~951.5 | 0.992 | 0.9847(0.979~0.99) | 7.0335(5.453~8.614) | 260.56 | 263.61 |
The Correlation and Estimated Bias of BC-3600 (Combined) (vs BC-Table 1: 3200)
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| Parameters | Result Range | ﻟﻘ | slope(95%CI) | intercept(95%CI) | Mean | |
|---|---|---|---|---|---|---|
| Predicate | Test | |||||
| MPV(fL) | 6.3 ~ 11.8 | 0.865 | 0.793(0.773~0.813) | 1.6200(1.452~1.788) | 8.48 | 8.34 |
The WBC flagging rate for the BC-3600 was compared to the WBC manual differential for the same population of samples as shown in Table 2.
Table 2: The WBC Flagging Ability of BC-3600 (Combined) (vs Manual)
| BC-3600 | |
|---|---|
| True Positive | 178 |
| True Negative | 739 |
| False Positive | 227 |
| False Negative | 64 |
| Total | 1208 |
| Sensitivity (TP %) | 73.6% |
| Specificity (TN %) | 76.5% |
| Efficiency | 75.9% |
Precision/Reproducibility
Reproducibility study was performed on BC-3600 to evaluate the long term imprecision of the device using three level of control material (BC-3D control Low, Normal and High) for complete blood counts and leukocyte 3 Part Differential parameters. Each level control samples were run in duplicated twice each day for 20 days on the BC-3600 analyzer at each of the three clinical sites. Data were analyzed for each site and for the combined data from all sites used the same lot control according to the guidance provided in CLSI EP5-A2. For each site, the standard deviation (SD) and coefficient of variation (CV%) for within-run, between-run, between-day, and within-device were estimated. For the combined data from two clinical sites, the SD and CV% for within-run, between-run, between-day, between-device and total precision were calculated also. The reproducibility results in each site met the specifications.
Precision/Repeatability
To demonstrate the within-run precision as a coefficient of variation from replicates of a single sample, ten replicates of K2EDTA whole blood samples around medical decision levels and the upper and lower limit of the analytical measuring range. Sample were selected and tested in the whole blood mode or the predilute mode at three clinical sites
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respectively. The mean, standard deviation (SD), and coefficient of variation (CV) were calculated for each sample. All data in each site passed specifications.
Linearity Range
WBC and PLT high-value analogs, which come from commercialized materials, were diluted to different values respectively. RBC/HGB linearity was performed using dilutions prepared from fresh whole blood. The whole blood was concentrated to obtain specimens to test the high linearity limit. Serial dilutions were prepared using the diluent for each parameter to create 7 subsequent dilutions. The mean of multiple measurements, three (3), from each of the 7 dilutions across the linearity range were used. Acceptable performance is indicated by the data fitting a linear regression line with a coefficient of determination (R2) of >0.95 and the parameters measured recovering within the bias limits for each parameters based on CLSI EP06-A.
Carryover
Carryover was determined for WBC, RBC, HGB and PLT. Testing was performed to test the different analytical cycle combinations of within mode for whole blood, within mode for predilute and mode. For each analytical cycle combination, whole blood and predilute sample with extremely elevated blood components (high sample) and with decreased blood components (low sample) were tested in triplicates according to H26-A2.
For whole blood and predilute sampling, within mode to mode for sampling carryover were calculated and the results were within specifications (≤ 0.5%) for WBC, RBC, HGB and (< 1.0%) for PLT. BC-3600 Analyzer demonstrated minimum carryover level within the defined specification for both Whole Blood and Predilute mode listed below.
Interference
The potential interfering substances of BC-3600 were found to be the same as the predicate BC-3200 analyzer due to the fact that the two devices had very similar principle. The interference studies of Bilirubin, Intralipid, and High WBC were performed for BC-3600 at one clinical site. The impact of those substances were analyzed and the results demonstrated that the elevated concentration of Bilirubin, Intralipid, or WBC in a sample will impact its measurement results on BC-3600. This exact same interference substances limitation can be found in predicate device BC-3200 (K093394).
Other Compatibility Studies
Comparison of Whole Blood Mode and Predilute Mode Sample
To demonstrate that BC-3600 analyzer performs equally on samples tested in different analysis modes. 61 pairs of samples representing the normal and medical conditions were
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collected in K2EDTA collection tube. All the samples were tested on BC-3600 analyzer with Whole blood mode and Predilute mode. The results were analyzed using StatisPro software according to CLSI EP09-A3 and showed that there was no difference when testing samples in either mode or when the sample contained parameters in normal or abnormal range due to medical conditions.
Comparison of Venipuncture and Fingerstick Sample
To demonstrate the comparable performance between capillary samples and the venous samples, 52 pair specimens were collected from donor by capillary method in K₂EDTA microtainer and venipuncture method in K2EDTA collection tube. Specimen levels were selected to cover the analytical measuring interval and medical decision levels for each parameter. Each sample was tested in the whole blood mode at the U.S. site. The results were analyzed using StatisPro software according to CLSI EP09-A3 and showed that the performance characteristics of the two specimen types were comparable.
Comparison of K2EDTA and K3EDTA Anticoagulants Samples
To evaluate whether samples collected in K2EDTA and K3EDTA have the same performance characteristics on BC-3600 analyzer, 60 paired fresh whole blood samples collected in K2EDTA and K3EDTA anticoagulant tubes were tested. The samples were selected with the targets to cover the analytical measuring interval and medical decision levels for each parameter. Each sample is tested in whole blood mode on BC-3600 at actual user site in the U.S. The results were analyzed using StatisPro software according to CLSI EP09-A3 and showed that the performance characteristics of the specimens collected in the two anticoagulants are comparable.
Sample Stability
To test the time that the samples can be stored at certain conditions after collection and before testing without compromising the performance characteristic, whole blood and pre-dilute whole blood stability studies were performed with specimens collected in K2EDTA anticoagulants. For the whole blood samples stability, a total of 35 normal and abnormal samples have been collected in the Finlay Laboratory (U.S. site) on BC-3600 analyzer. In addition, a total of 25 normal and abnormal samples have been collected in the NSH site for the predilute sample stability on BC-3600. Aliquots were prepared and stored at the defined condition for each specimen, then analyzed in duplicate at different time points according to the study design. When samples are stored for the durations defined at controlled room temperature [64-79° F (18-26° C)] or at refrigerated temperature [35.6-46.4° F (2-8° C)] the analyzer performance results met the acceptance limits according to CLSI EP25-A . The whole blood is stable for 24 hours at refrigerated temperature (2-8° C) and 12 hours when stored at 18-26° C for all parameters (except for the differential parameters Gran#/%, Mid#/%, Lymph#/% which are stable for 8 hours
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when stored at 18-26° C). Predilute whole blood stability is 30 minutes when stored at 18-26° C after preparation and before testing for all parameters.
Reference Interval
A study was performed to assess the Adult Reference Ranges for BC-3600 analyzer using whole blood samples collected from 255 donors. In the study 124 adult male donors and 131 adult female donors between the ages of 19-85 were included. The non-parametric method and 95% confidence were used to calculate the lower and upper limits of the reference range according to C28-A3. The results are all shown in Table 3.
It is recommended that laboratories establish their own reference range based on the actual current patient population.
| Parameters | Partitions | Male | Female | Combined | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| (Femalevs Male) | N | Low Limit(90%CI) | Upper Limit(90%CI) | N | Low Limit(90%CI) | Upper Limit(90%CI) | N | Low Limit(90%CI) | Upper Limit(90%CI) | |
| WBC | NO | 125 | 4.12(4.00~4.50) | 12.27(10.30~13.40) | 131 | 4.23(3.30~4.50) | 13.21(11.10~13.80) | 256 | 4.20(4.00~4.50) | 12.36(11.00~13.60) |
| Lymph# | YES* | 125 | 1.00(0.50~1.10) | 3.70 (3.30~4.30) | 131 | 0.89(0.60~1.20) | 5.14 (3.80~6.10) | 256 | 1.00(0.80~1.10) | 4.16 (3.70~5.50) |
| Mid# | YES* | 125 | 0.40(0.30~0.40) | 1.47 (1.10~2.00) | 131 | 0.23(0.20~0.30) | 1.10 (1.00~1.20) | 256 | 0.30(0.20~0.40) | 1.20 (1.10~1.50) |
| Gran# | NO | 125 | 2.10(1.80~2.20) | 8.64 (7.50-8.90) | 131 | 2.03(1.80~2.20) | 7.61(7.10~10.00) | 256 | 2.10(2.00~2.20) | 8.26 (7.10~8.80) |
| Lymph% | NO | 125 | 14.83(8.50~18.50) | 45.40(43.80~62.90) | 131 | 15.72(11.40~18.80) | 50.75(46.20~57.00) | 256 | 14.89(11.40~18.50) | 47.52(45.40~52.50) |
| Mid% | YES* | 125 | 4.82(4.40~5.70) | 16.18(12.60~30.50) | 131 | 4.43(4.20~4.60) | 13.93(12.30~14.90) | 256 | 4.54(4.40~4.80) | 14.56(12.60~16.30) |
| Gran% | NO | 125 | 43.62(31.10~46.50) | 77.06(74.80~82.40) | 131 | 40.36(36.40~44.10) | 78.18(74.00~83.00) | 256 | 42.24(37.80~45.50) | 77.06(74.70~80.90) |
| RBC | YES* | 125 | 3.583(3.320~3.830) | 5.856(5.600-6.410) | 131 | 3.528(3.300~3.730) | 5.704(5.340~6.430) | 256 | 3.559(3.370~3.770) | 5.792(5.590~6.410) |
| HGB | YES* | 125 | 10.59(9.80~11.90) | 17.36(16.90~18.00) | 131 | 10.43(10.10~11.00) | 16.04(15.60~16.20) | 256 | 10.50(10.20~11.30) | 16.90(16.70~17.40) |
| HCT | YES* | 125 | 33.74(30.00~35.60) | 50.90(50.20~52.40) | 131 | 33.60(31.10~34.30) | 47.42(46.10~48.40) | 256 | 33.60(31.90~34.60) | 50.32(48.60~50.90) |
| MCV | NO | 125 | 77.13(64.90~82.90) | 100.91(99.40~103.00) | 131 | 71.28(66.40-81.30) | 99.91(97.70~101.10) | 256 | 75.67(69.70~81.30) | 100.09(98.60~101.10) |
| MCH | NO | 125 | 24.75(20.50~27.50) | 33.87(33.10~35.10) | 131 | 22.14(20.70~26.40) | 33.47(32.60~34.10) | 256 | 23.73(21.70~26.70) | 33.56(33.10~34.10) |
| MCHC | YES* | 125 | 31.52(31.20~32.20) | 34.90(34.80~35.60) | 131 | 31.03(30.00~31.60) | 34.50(34.40~36.10) | 256 | 31.24(31.00~31.80) | 34.90(34.80~35.20) |
| RDW | NO | 125 | 11.80(11.40~11.90) | 15.83(14.70~17.20) | 131 | 11.53(11.40~11.80) | 15.22(14.60~17.50) | 256 | 11.64(11.40~11.80) | 15.40(14.80~16.60) |
| PLT | YES* | 125 | 145.0(79.0~168.0) | 368.7(361.0~515.0) | 131 | 159.0(111.0~169.0) | 456.6(415.0~565.0) | 256 | 157.3(136.0~167.0) | 435.5(401.0~515.0) |
| MPV | NO | 125 | 6.72(6.50~7.00) | 9.60 (9.30-9.90) | 131 | 6.90(6.40~7.10) | 10.01(9.50~11.20) | 256 | 6.84(6.60~7.00) | 9.80(9.50~10.10) |
The Reference Intervals of BC-3600 Table 3:
YES*: denoted that a separate reference interval should be considered for the partitions of Male and Female.
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Determination of Limit of Blank (LoB), Limits of Detection (LoD) and Limit of Quantitation (LoQ)
Limit of Blank was determined using five blank samples (diluent) which just contain the predilute solution. To determine the Limits of Detection and Limit of Quantitation, five low levels of samples were created by adding whole blood samples to dilutent to reach approximately 4 times of the LoB. Each blank sample or low level sample is tested for 12 times at one clinical laboratory in China tested in the whole blood mode on three BC-3600 analyzer and the low level samples are tested for 5 times on BC-3200 analyzer. The results were analyzed according to CLSI EP17-A. The LoB on the BC-3600 for WBC is 0 x 10^3/uL, PLT is 2.1 x 10^3/uL. The LoB and LoD on the BC-3600 for WBC is 0.05 x 10^3/uL, PLT is 3.4 x 10^3/uL.
Substantial Equivalence
Table 4 and Table 5 summarize the similarities and differences between the BC-3600 Hematology and the predicate device.
| Similarities | ||
|---|---|---|
| Item | BC-3600 | Predicate BC-3200 |
| Intended Use | The BC-3600 auto hematology analyzer isa quantitative, automated hematologyanalyzer for in vitro diagnostic use inclinical laboratories. The BC-3600 autohematology analyzer provide completeblood count (WBC, RBC, HGB, HCT,MCV, MCH, MCHC, RDW, PLT, MPV)and leukocyte 3-Part differential (Lymph#,Mid#, Gran#, Lymph%, Mid%, Gran%)for whole blood specimens, collected in asalt of EDTA [dipotassium (K2) ortripotassium (K3)] obtained byvenipuncture or fingerstick. The purpose ofthe BC-3600 Auto Hematology Analyzeris to identify the normal human patient,with normal system-generated parameters,from patients whose results requireadditional studies. | The BC-3200 auto hematologyanalyzer is a quantitative,automated hematology analyzerand leukocyte differentialcounter to be used in clinicallaboratories for In VitroDiagnostic purpose. Theintended use of BC-3200 AutoHematology Analyzer is toidentify the normal patient, withall normal system-generatedparameters, and to flag oridentify patient results thatrequire additional studies. |
| Similarities | ||
| Test Principle | WBC, RBC, MCV, RDW, PLT and MPV:Coulter principle of Impedance methodHGB: Colorimetric methodWBC Differential: Instrument calculates athree population leukocyte count(Lymph%, Mid%, Gran%) from the WBChistogram based on cell size determined byimpedance method. The absolute numberfor each population is then calculated. | Same |
| Sample Type | Whole blood | Same |
| SamplingMechanism | Manual presentation for closed vialsampling whole blood analysis and pre-dilute analysis mode | Same |
| SampleProcessing | Utilizes an automatic sampling, dilutingand mixing device for sample processing | same |
| Sample ID | Manual barcode scan of sample tubeidentifier or manual keyboard entry ofsample identifier | Same |
| Parameters | Parameters(16):WBC, Lymph#, Mid#, Gran#, Lymph%,Mid%, Gran%, RBC, HGB, HCT, MCV,MCH, MCHC, RDW, PLT, MPV | Same |
| Data Analysis | Analyze analog raw data to generatereported parameters | Same |
| Data Reporting | Display, printing and transmission of datato LIS/HIS. | Same |
| SystemThroughput | 60 samples per hour | Same(1 minute / analysis) |
| Software RiskLevel | Moderate | Same |
| Mode ofOperation | Whole Blood Closed Vial Analysis ModePre-dilute Analysis Mode | Same |
| AnalysisReagents | M-30D DILUENTM-30CFL LYSEM-30R RINSE | Same |
| Controls | BC-3D Controls - 3 Levels | Same |
| Calibrators | SC-CAL PLUS Calibrator | Same |
| Similarities | ||
| Analysis Mode | Whole Blood Mode and Pre-dilute Mode | Same |
| Quality ControlTechniques | L-J Analysis and X-B Analysis | Same |
| SamplePreparation | Syringe for sample aspiration / deliveryand also for reagent delivery | Same |
Device Comparison Table - Similarities Table 4:
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Table 5: Device Comparison Table - Differences
| Differences | ||
|---|---|---|
| Item | BC-3600 | Predicate BC-3200 |
| SampleAnticoagulant | K2EDTA or K3EDTA | K2EDTA only |
| CleaningAgents | PROBE CLEANSER | M-30P PROBE CLEANSERM-30E E-Z CLEANSER |
| SampleAspirationVolume | 21 µL of whole blood in wholeblood analysis mode20µL of blood to prepare a pre-diluted sample for the Pre-diluteanalysis mode | 13 µL of whole blood in the wholeblood analysis mode20µL of blood to prepare a pre-diluted sample for the Pre-diluteanalysis mode |
| Display | TFT Color Touch Screen,800×600 pixels | Color LCD, 10.4'', 800x600 pixels |
| I/O Interfaces | - One LAN interface, built-innetwork card, TCP/IP compatible- One RS-232 port to support thehost connected to LIS with serialport- 4 USB ports | - One keyboard interface- Two RS-232 interfaces- One parallel port- One power supply for the floppydisk drive |
Substantial Equivalence Conclusion
The BC-3600 Auto Hematology Analyzer has the exact same intended use as the predicate device, the BC-3200 as cleared in K093394. Both the BC-3600 Auto Hematology Analyzer and the predicate use the same technology as a quantitative, automated hematology analyzer and leukocyte differential counter for In Vitro Diagnostic Use in clinical laboratories. These analyzers may be used in adult and pediatric population. Both analyzers are only to be used by trained medical professionals to identify the normal patient, with all normal system-generated parameters, and to flag or identify patient results that require additional studies. The analyzer provides analysis
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results of 16 parameters of human blood and three histograms. The minor differences are tested for their performance impact. The results demonstrated that they do not impact substantial equivalence.
§ 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.”