(160 days)
The BC-3200 auto hematology analyzer is a quantitative, automated hematology analyzer and leukocyte differential counter to be used in clinical laboratories for In Vitro Diagnostic purpose. The intended use of BC-3200 Auto Hematology Analyzer is to identify the normal patient, with all normal system-generated parameters, and to flag or identify patient results that require additional studies.
The BC-3200 Auto 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 (listed below) of human blood and three histograms. The BC-3200 Auto Hematology Analyzer system consists of the analyzer, reagents (M-30D DILUENT, M-30R RINSE, M-30CFL LYSE, M-30E E-Z CLEANSER and M-30P PROBE CLEANSER), controls (BC-3D Hematology Control), calibrator (SC-CAL PLUS Hematology Calibrator) and accessories. The two independent measurement methods used in this analyzer are: the Coulter method for determining the WBC, RBC, and PLT data and the colorimetric method for determining the HGB.
Here's a summary of the acceptance criteria and study details for the BC-3200 Auto Hematology Analyzer, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally implied by the performance characteristics tested and compared to a predicate device (COULTER® AC-T diff 2™ Analyzer) and/or established laboratory standards (e.g., CLSI guidelines for reproducibility, linearity). The provided document mostly reports the observed performance without explicit pre-defined "acceptance criteria" values in all cases, but rather demonstrates that the device performs comparably to the predicate or meets general expectations for such a device. Where specific target criteria are stated (e.g., for carryover), they are included.
| Performance Characteristic | Parameter | Acceptance Criteria (Implied/Stated) | Device Performance (Reported) |
|---|---|---|---|
| Reproducibility | WBC (CV%) | - | Low: 0.99 - 1.84% |
| Normal: 0.99 - 1.18% | |||
| High: 0.93 - 1.85% | |||
| RBC (CV%) | - | Low: 1.06 - 1.76% | |
| Normal: 0.73 - 0.78% | |||
| High: 0.60 - 1.24% | |||
| HGB (CV%) | - | Low: 0.8 - 1.1% | |
| Normal: 0.4 - 0.8% | |||
| High: 0.7 - 0.8% | |||
| MCV (CV%) | - | Low: 0.28 - 0.62% | |
| Normal: 0.25 - 0.45% | |||
| High: 0.71% | |||
| PLT (CV%) | - | Low: 3.12 - 8.39% | |
| Normal: 1.95 - 3.70% | |||
| High: 1.58 - 2.32% | |||
| Inter-Laboratory Precision | WBC (CV%) | - | Low: 2.35% |
| Normal: 1.95% | |||
| High: 1.20% | |||
| Gran (CV%) | - | Low: 5.20% | |
| Normal: 1.46% | |||
| High: 0.49% | |||
| Lymph (CV%) | - | Low: 3.60% | |
| Normal: 4.09% | |||
| High: 6.02% | |||
| Mid (CV%) | - | Low: 4.36% | |
| Normal: 2.86% | |||
| High: 8.84% | |||
| RBC (CV%) | - | Low: 1.34% | |
| Normal: 1.81% | |||
| High: 1.59% | |||
| HGB (CV%) | - | Low: 1.11% | |
| Normal: 1.78% | |||
| High: 1.71% | |||
| MCV (CV%) | - | Low: 1.99% | |
| Normal: 1.43% | |||
| High: 1.74% | |||
| PLT (CV%) | - | Low: 5.56% | |
| Normal: 3.60% | |||
| High: 1.89% | |||
| Linearity | WBC | Error acceptance criteria not explicitly stated, but comparable to predicate's ±0.3 or ±5% | Proportional error up to 32.4% for lowest concentration (0.625%), but generally within +/- 5% for concentrations 2.5% and above. |
| RBC | Error acceptance criteria not explicitly stated, but comparable to predicate's ±0.05 or ±5.0% | Proportional error up to -6.9% for 5% dilution, generally within +/- 3.6% for higher dilutions. | |
| HGB | Error acceptance criteria not explicitly stated, but comparable to predicate's ±0.2 or ±3.0% | Proportional error up to -2.7% for 10% dilution, generally within +/- 1.7% for higher dilutions. | |
| PLT | Error acceptance criteria not explicitly stated, but comparable to predicate's ±10.0 or ±10.0% | Proportional error up to 55.2% for 1.25% dilution, but generally within +/- 27.3% for concentrations 2.5% and above. Error generally higher at very low concentrations. | |
| Carryover | WBC | 0.5% or less | 0% (in both whole blood and high level control tests) |
| RBC | 0.5% or less | 0.46% (whole blood), 0% (high level control) | |
| HGB | 0.5% or less | 0.46% (whole blood), 0% (high level control) | |
| PLT | 1.0% or less | 0% (in both whole blood and high level control tests) | |
| Correlation to Predicate Device | All parameters | Correlation coefficients (r) close to 1, small difference ratio/slope ~1, intercept ~0. | WBC: r=0.9990 |
| Gran%: r=0.9581 | |||
| Mid%: r=0.3926 (not strong) | |||
| Lymph%: r=0.9709 | |||
| Gran#: r=0.9961 | |||
| Mid#: r=0.8701 | |||
| Lymph#: r=0.9886 | |||
| RBC: r=0.9955 | |||
| HGB: r=0.9972 | |||
| HCT: r=0.9923 | |||
| MCV: r=0.9778 | |||
| MCH: r=0.9712 | |||
| MCHC: r=0.6038 (not strong) | |||
| RDW: r=0.9387 | |||
| PLT: r=0.9943 | |||
| MPV: r=0.9169 | |||
| Correlation to Manual Differential | Lymph% | Correlation coefficient (r) close to 1. | r=0.95 |
| Mid% | Correlation coefficient (r) close to 1. | r=0.57 (not strong) | |
| Gran% | Correlation coefficient (r) close to 1. | r=0.94 | |
| WBC Histogram Flagging | Agreement | Implied satisfactory agreement for flagging. | Agreement: 82.5% |
| False Positive Ratio: 10.6% | |||
| False Negative Ratio: 45% |
2. Sample Sizes Used for Test Set and Data Provenance
- Reproducibility (within-run): N=11 replicates for 3 low, 3 normal, and 3 high concentration samples (n=9 samples total). Data provenance is not specified, but implied to be from internal lab testing.
- Inter-Laboratory Precision: 3 samples (low, normal, high concentrations), each run twice at two different laboratories. Data provenance is not specified, but implied to be from internal lab testing involving two labs.
- Linearity: Diluted samples (concentrations from 0 to 100%), each concentration run twice. Data provenance is not specified.
- Carryover: High concentration sample run 3 times, then low concentration sample run 3 times. Also, high level control run 3 times, then specified diluent run 3 times. Data provenance is not specified.
- Correlation to Predicate Device: 103 samples for CBC parameters (WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV). 98 samples for differential parameters (Gran%, Mid%, Lymph%, Gran#, Mid#, Lymph#). Data provenance is not specified (e.g., country of origin, retrospective/prospective).
- Correlation to Manual Differential: 196 samples for differential parameters (Lymph%, Mid%, Gran%). Data provenance is not specified.
- Ability to flag abnormal WBC histograms: 200 samples. Data provenance is not specified.
- Reference Ranges (Normal Population Study): 121 donors. Data provenance is not specified (e.g., country of origin, retrospective/prospective).
3. Number of Experts and Qualifications for Ground Truth (Test Set)
- Correlation to Manual Differential: The text states "comparing the DIFF results obtained by the BC-3200 to those by manual differential." This implies that manual differential counts performed by trained laboratory personnel served as the ground truth. The number of experts and their specific qualifications (e.g., years of experience, specific certifications) are not specified in the document.
- Ability to flag abnormal WBC histograms: The comparison was "to those obtained by manual differential." Similar to the above, this implies manual review by trained personnel as ground truth, but the number and qualifications of experts are not specified.
4. Adjudication Method (Test Set)
- The document does not specify any explicit adjudication method (e.g., 2+1, 3+1) for establishing ground truth for any of the studies mentioned. It simply refers to "manual differential" or "Coulter A.T diff 2™" as comparators/ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not explicitly described or conducted for human readers with and without AI assistance. The document focuses on the performance of the device itself (standalone) compared to a predicate device and manual methods.
6. Standalone Performance (Algorithm Only) Study
- Yes, a standalone study was performed. All the performance characteristics described (reproducibility, inter-laboratory precision, linearity, carryover, correlation to predicate, correlation to manual differential, ability to flag abnormal histograms, reference ranges) are evaluations of the BC-3200 Auto Hematology Analyzer's performance without direct human intervention in the result generation itself. The comparisons to manual differential and the predicate device assess its standalone accuracy and equivalence.
7. Type of Ground Truth Used
- Expert Consensus / Expert Reading (Manual Differential): For differential parameters (Lymph%, Mid%, Gran%) and WBC histogram flagging, the ground truth was based on "manual differential" performed by laboratory personnel. This typically involves microscopic review and counting of cells by trained experts.
- Reference Instrument/Method (Predicate Device): For most CBC and differential parameters, the BC-3200 was correlated against the COULTER® AC-T diff 2™ Analyzer, which served as a reference standard.
8. Sample Size for the Training Set
- The document does not specify a separate training set or its sample size. The studies described are performance validation studies. For a device like this, the "training" (i.e., algorithm development and calibration) might have occurred during the design phase using internal datasets, which are not detailed in this submission summary. The "Reference Ranges" study involved 121 donors, which could be considered a dataset used for defining normal operating parameters, but not explicitly a training set for an AI/ML algorithm.
9. How Ground Truth for the Training Set was Established
- As a training set is not explicitly mentioned or described, the method for establishing its ground truth is also not specified in this document.
§ 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.”