(576 days)
The Alinity h-series System is an integrated hematology analyzer (Alinity hq) and slide maker stainer (Alinity hs) intended for screening patient populations found in clinical laboratories by qualified health care professionals. The Alinity h-series System can be configured as:
- · One standalone automated hematology analyzer system.
· A multimodule system that includes at least one Alinity hq analyzer module and may include one Alinity hs slide maker stainer module.
The Alinity hq analyzer module provides complete blood count and a 6-part white blood cell differential for normal and abnormal cells in capillary and venous whole blood collected in K2EDTA. The Alinity hq analyzer provides quantitative results for the following measurands: WBC, NEU, %N, MON, %M, EOS, %E, BASO, %B, 1G, %IG, RBC, HCT, HGB, MCV, MCH, MCHC, MCHr, RDW, NRBC, NR/W, RETIC, %R, IRF, PLT, MPV, %oP. The Alinity hq analyzer module is indicated to identify patients with hematologic parameters within and outside of established reference ranges. The Alinity hs slide maker stainer module automates whole blood film preparation and staining and stains externally prepared whole blood smears.
For in-vitro diagnostic use.
The Alinity h-series system is a multimodule system that consists of different combinations of one or more of the following modules: a quantitative multi-parameter automated hematology analyzer (Alinity hg) and an automated slide maker stainer (Alinity hs).
The modules are designed to fit together. Each module has an internal conveyor that enables racks of specimen tubes to be transported between modules. The system can move racks between modules to perform different tests on a given specimen (e.g., make slide smears on the Alinity hs).
Here's an analysis of the acceptance criteria and supporting studies for the Abbott Laboratories Alinity h-series System, based on the provided FDA 510(k) summary:
Key Takeaways from the Document:
- This 510(k) pertains to the Abbott Alinity h-series System, an integrated hematology analyzer (Alinity hq) and slide maker stainer (Alinity hs).
- The device provides complete blood count and a 6-part white blood cell differential.
- The comparison is primarily against a predicate device: Sysmex® XN-Series (XN-10, XN-20) Automated Hematology Analyzers (K112605).
- The studies presented focus on analytical performance demonstrating substantial equivalence, rather than a comparative effectiveness study with human readers (MRMC).
1. Table of Acceptance Criteria and Reported Device Performance
The document details performance against predefined acceptance criteria, which are largely implied through the presentation of results being "within the predefined acceptance criteria and found to be acceptable." Specific quantitative acceptance criteria are not explicitly stated in a single table but are indicated to have been met for each study type.
Here’s a consolidated table, inferring the acceptance goals from the reported measurements and statistical analyses (e.g., correlation coefficients, bias estimates, precision, sensitivity, specificity).
| Performance Metric Category | Specific Metric / Test | Acceptance Criteria (Implicit from "All results met...") | Reported Device Performance and Results (Alinity h-series vs. Sysmex® XN-Series where applicable) |
|---|---|---|---|
| Method Comparison | Passing-Bablok/Deming Regression Analysis (r, Slope, Intercept), Bias at Critical Points | Acceptable correlation (high r), slope near 1, intercept near 0; Bias within predefined limits | Correlation Coefficient (r): Mostly 0.95 - 1.00 (with some exceptions like %B, %IG, BASO, MCHC, %rP) |
| Slope: Mostly ~1.00 | |||
| Intercept: Mostly ~0.00 | |||
| Bias: Reported for various measurands at critical points, and stated to be "within the predefined acceptance criteria and found to be acceptable." Sample sizes range from 1545 to 2006 for different measurands | |||
| Sensitivity & Specificity (Morphological/Distributional Abnormalities) | Sensitivity (for flags) | Within predefined acceptance criteria | Sensitivity: 80.19% (95% CI: 75.38%, 84.43%) |
| Specificity (for flags) | Within predefined acceptance criteria | Specificity: 76.40% (95% CI: 71.64%, 80.72%) | |
| Efficiency (for flags) | Within predefined acceptance criteria | Efficiency: 78.19% (95% CI: 74.88%, 81.25%) | |
| Precision (Repeatability) | Mean, SD, CV, 95% CI for various measurands | CVs and SDs within predefined acceptance criteria | Presented for 32 unique donors (16 normal, 16 pathological), stating "All results met the predefined acceptance criteria." |
| System Reproducibility | Between-run, Between-day, Within-laboratory, Betweendevice variance components | CVs and SDs within predefined acceptance criteria | Presented for control levels (low, normal, high), stating "All results met the predefined acceptance criteria." |
| Linearity | Linear Range for key measurands (RBC, HGB, NRBC, WBC, PLT, RETIC) | Demonstrated linearity across specified ranges | RBC: 0.00 – 8.08 x 10^6 /μL |
| HGB: 0.04 – 24.14 g/dL | |||
| NRBC: 0.00 – 26.10 x 10^3 /μL | |||
| WBC: 0.00 – 449 x 10^3 /μL | |||
| PLT: 0.06 – 5325 x 10^3 /μL | |||
| RETIC: 0.05 – 644 x 10^3 /μL. Stated "All results met the predefined acceptance criteria." | |||
| Carryover | Absence of significant carryover | Within predefined acceptance criteria | Stated "All results met the predefined acceptance criteria." |
| Interfering Substances | Impact of hemoglobin, triglycerides, bilirubin, cholesterol, elevated WBCs/RBCs/PLTs, microcytic RBCs | Measurands impacted should remain within acceptable limits or flags triggered appropriately | Identified specific measurands impacted by certain interferents. Stated "All results met the predefined acceptance criteria." |
| Limits of Blank, Detection, Quantitation (LoB, LoD, LoQ) | Values for WBC, RBC, HGB, PLT | Within predefined acceptance criteria | WBC: LoB 0.01, LoD 0.02, LoQ 0.03 |
| RBC: LoB 0.00, LoD 0.01, LoQ 0.01 | |||
| HGB: LoB 0.08, LoD 0.11, LoQ 0.05 | |||
| PLT: LoB 0.15, LoD 0.38, LoQ 0.29. Stated "All results met the predefined acceptance criteria." | |||
| Specimen Stability | Stability of venous and capillary samples over time and temperature | Maintain stability for specified periods (e.g., up to 24-48 hours at specific temperatures) | Supports information provided in system labeling for venous and capillary specimen stability. |
| Anticoagulant Comparability (K3EDTA vs. K2EDTA) | Mean difference or % difference, Regression analysis | Bias within predefined acceptance criteria | Stated "All reportable parameters that were evaluated met their predefined bias acceptance criteria." |
| Microtainer Capillary vs. Microtube for Automated Process (MAP) Comparability | Mean difference or % difference, Regression analysis | Bias within predefined acceptance criteria | Stated "All reportable parameters that were evaluated met their predefined bias acceptance criteria." |
| Matrix Comparability (Capillary vs. Venous) | Mean difference or % difference, Regression analysis | Bias within predefined acceptance criteria | Stated "All reportable parameters that were evaluated met their predefined bias acceptance criteria." |
| Sample/Tube Processing Mode Comparability (Open vs. Closed) | Mean difference or % difference, Regression analysis | Bias within predefined acceptance criteria | Stated "All reportable parameters that were evaluated met their predefined bias acceptance criteria." |
| Reference Intervals | Establishment of adult & pediatric reference intervals | Statistically derived and verified reference intervals | Established for adult (> 21 yrs) and pediatric (≤ 21 yrs) populations, including subgroups for neonates, infants, children, and adolescents. |
2. Sample Size Used for the Test Set and Data Provenance
-
Method Comparison:
- Sample Size: 2,194 unique venous and/or capillary specimens.
- Data Provenance: Not explicitly stated by country, but mentions "7 clinical sites" which implies a multi-center study. The specimens were from pediatric (≤ 21 years) and adult (> 21 years) subjects, including a wide variety of disease states (clinical conditions). This indicates a prospective collection for the purpose of the study.
-
Sensitivity and Specificity:
- Sample Size (N for analysis): 674 samples for the "Any Morphological Flags and/or Distributional Abnormalities" category. (Individual Ns for TP, FP, FN, TN are provided in the table).
- Data Provenance: Not explicitly stated by country, but implies multiple sites as it refers to "All Sites Combined – Sensitivity and Specificity." Specimens were venous and capillary. No explicit mention of retrospective/prospective, but implies collection for the study.
-
Precision (Repeatability):
- Sample Size: 32 unique donors (16 normal, 16 pathological).
- Data Provenance: Not explicitly stated, implied prospective collection for the study.
-
System Reproducibility:
- Sample Size: A single lot of Alinity h-series 29P Control (low, normal, high) tested across "three clinical sites" for 5 days with 3 runs/day and a minimum of 2 replicates/run. The N for calculations (e.g., WBC, Low) is 84.
- Data Provenance: Not explicitly stated for country, but multi-site. Implied prospective testing.
-
Linearity:
- Sample Size: 9 levels, 4 replicates each, for RBC, HGB, NRBC, WBC, PLT, RETIC.
- Data Provenance: Not explicitly stated, implied prospective testing.
-
Carryover:
- Sample Size: Minimum of 4 carryover runs at each of 4 testing sites (minimum 16 total runs per measurand) using high and low target specimens.
- Data Provenance: Not explicitly stated for country, multi-site. Implied prospective testing.
-
Potentially Interfering Substances:
- Sample Size: Samples tested for the presence of various interferents. No specific N provided.
- Data Provenance: Not explicitly stated.
-
Limits of Blank, Detection, and Quantitation (LoB, LoD, LoQ):
- Sample Size: Minimum of 3 days, 2 unique samples/day, 2 test selections, 5 replicates, 2 reagent lots. No specific overall N provided.
- Data Provenance: Not explicitly stated.
-
Specimen Stability:
- Sample Size: Minimum of 10 abnormal and 10 normal venous specimens (K2EDTA/K3EDTA); minimum of 20 normal capillary specimens (K2EDTA/K3EDTA).
- Data Provenance: Not explicitly stated.
-
Anticoagulant Comparability (K3EDTA vs. K2EDTA):
- Sample Size: 199 unique adult and pediatric donor sets.
- Data Provenance: Not explicitly stated.
-
Microtainer Capillary vs. Microtube for Automated Process (MAP) Comparability:
- Sample Size: 44 unique donor sets (normal whole blood specimens).
- Data Provenance: Not explicitly stated.
-
Matrix Comparability (Capillary vs. Venous):
- Sample Size: 76 unique venous and capillary donor sets (normal and abnormal).
- Data Provenance: Not explicitly stated.
-
Sample/Tube Processing Mode Comparability (Open vs. Closed Mode):
- Sample Size: 226 unique venous specimens.
- Data Provenance: Not explicitly stated.
-
Reference Intervals:
- Adults: 261 unique venous and 1 capillary whole blood specimens from 126 male and 136 female adult subjects.
- Pediatric: 360 venous or capillary specimens (61 neonates, 68 infants, 109 children, 122 adolescents).
- Data Provenance: Not explicitly stated for country. "Apparently healthy subjects."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The document does not mention the use of experts to establish ground truth for the test set in the context of diagnostic interpretation (e.g., classifying morphological flags from blood films). The "ground truth" for the analytical performance studies (e.g., method comparison, precision) appears to be derived from the predicate device (Sysmex® XN-Series) or established analytical methods.
For the Sensitivity & Specificity study related to identifying distributional abnormalities and morphological flags using blood films, it states the study was "assessed by identifying distributional abnormalities and morphological flags using blood films." This implies a reference method of manual microscopy for validation, which typically involves expert review. However, the number and qualification of experts used to establish this blood film ground truth are not specified in this summary.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method (like 2+1, 3+1, or none) for establishing ground truth for any of the test sets mentioned (e.g., for morphological flags or disease classification). For analytical studies, the comparative method (predicate device) serves as the reference, not an adjudicated panel.
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 was not conducted or reported in this 510(k) summary. This document focuses on the analytical performance of the Alinity h-series System itself (an automated analyzer), demonstrating its substantial equivalence to a predicate automated analyzer. It is not an AI-assisted diagnostic device where human reader improvement would be a relevant metric.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented primarily represent the standalone performance of the Alinity h-series System. The "system" (Alinity hq analyzer module) performs quantitative measurements and differentiates blood cells without human intervention in the analytical process itself. The data reported (correlation, bias, precision, sensitivity/specificity of flags, linearity, etc.) reflect the device's performance as a standalone automated analyzer. The "sensitivity and specificity" study, while relying indirectly on blood film assessment (a human process) for its ground truth, measures the device's ability to trigger flags, which is a standalone function.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The type of ground truth varies by study:
- Method Comparison: The predicate device (Sysmex® XN-Series) served as the reference or "ground truth" for comparison purposes.
- Sensitivity & Specificity: This likely used manual microscopy via blood film review as the reference standard for identifying morphological and distributional abnormalities. The summary does not specify if this involved expert consensus or a single expert's reading.
- Precision, Reproducibility, Linearity, Carryover, LoB/LoD/LoQ determinations: These technical performance characteristics typically use controlled samples or reference materials with known values, or statistical calculations comparing device measurements to themselves.
- Interfering Substances, Specimen Stability, Anticoagulant/Matrix/Mode Comparability: These studies assess the device's performance under various conditions against its own baseline or expected performance, or against a comparative sample.
- Reference Intervals: Established by testing apparently healthy subjects and using statistical methods to define a range of typical values.
8. The sample size for the training set
The document does not explicitly mention a "training set" in the context of an algorithm or AI model development. Since the Alinity h-series System is described as using "flow cytometry and absorption spectrophotometry technologies," it's likely a rule-based or conventional instrument, not primarily an AI/ML-driven device requiring a distinct "training set" in the modern sense. The "rules based rerun / reflex" mentioned under software/hardware (page 8) refers to automated decision logic, not necessarily a machine learning model that undergoes training on a large dataset. Therefore, the concept of a "training set" as it relates to AI/ML is not directly applicable or discussed here.
9. How the ground truth for the training set was established
As there is no explicit mention of a "training set" for an AI/ML algorithm in this 510(k) summary, how its ground truth was established is not detailed. The device primarily relies on established analytical principles of flow cytometry and spectrophotometry.
§ 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.”