(134 days)
Caltag Cal-Lyse is a lysis solution to enable the lysis of erythrocytes in samples of anticoagulated human peripheral blood. Cal-Lyse lysing solution is intended as an aid in the enumeration of leukocytes that have been stained with Caltag monoclonal antibodies for analysis by flow cytometric methods.
Caltag monoclonal antibodies bind to the surfaces of viable blood cells that express the corresponding antigens. To identify cells bearing these antigenic determinants, peripheral blood samples are incubated with fluorochromeconjugated monoclonal antibodies. Cells are subsequently washed to remove unbound antibody. Prior to the removal of unbound antibody. Cal-Lyse lysing solution is added to lyse red blood cells. Cells may subsequently be washed. resulting in the elimination of red cell debris as well as unbound antibody. Cal-Lyse lysing solution contains paraformaldehyde as fixative, and no additional fixation is required. Antibody-stained and fixed leukocytes are subsequently analyzed by flow cytometric methods.
The document describes the Caltag Cal-Lyse™ Lysing Solution. The acceptance criteria and supporting studies are presented to demonstrate its substantial equivalence to predicate devices (Coulter CD19 monoclonal antibodies) when used for lysing red blood cells in flow cytometric procedures for enumerating leukocytes.
Please note that this is a summary of a 510(k) submission, focused on proving substantial equivalence to existing devices rather than a standalone AI performance study. Therefore, some of the requested categories (like number of experts, adjudication methods, MRMC studies, training set details) are not applicable or explicitly mentioned in the provided text, as they are typically relevant for novel AI/ML device evaluations.
Here's the breakdown of the information based on your request:
1. Table of Acceptance Criteria and Reported Device Performance
The concept of "acceptance criteria" is implicitly demonstrated through the "Substantially equivalent" comparison in the technical characteristics table and the high correlation (r^2 values) found in the clinical correlation data to the predicate devices. The performance is assessed by comparing the device with predicate devices in terms of intended use, specificity, target cell, chemical form, fluorochromes, available forms, sample prep methods, expected values, leukocyte recovery, and red blood cell lysis efficiency.
| Item | Acceptance Criteria (Implicit) | Reported Device Performance | Outcome |
|---|---|---|---|
| Intended Use | Substantially equivalent to predicate devices | Flow Cytometry | Substantially equivalent |
| Specificity | Substantially equivalent to predicate devices | CD19 | Substantially equivalent |
| Target Cell | Substantially equivalent to predicate devices | B lymphocyte | Substantially equivalent |
| Chemical Form | Substantially equivalent to predicate devices | Monoclonal antibody | Substantially equivalent |
| Fluorochromes | Substantially equivalent to predicate devices | R-PE, TRI-COLOR (Caltag) vs. FITC, RD1 (Coulter) | Substantially equivalent |
| Available Forms | Substantially equivalent to predicate devices | Liquid, PBS (Caltag) vs. Lyophilized, Liquid, PBS (Coulter) | Substantially equivalent |
| Sample Prep Methods | Substantially equivalent to predicate devices | Whole blood | Substantially equivalent |
| Expected Values (for CD19 R-PE, n=155) | Range comparable to predicate (4-21%) | 5-21% | Substantially equivalent |
| Leukocyte Recovery (Mean, n=5) | Comparable to predicate, high recovery | 90.8% (Caltag Cal-Lyse) and comparable to Ortho-mune | Acceptable |
| Red Blood Cell Lysis (Mean, n=5) | Greater than 90% in most cases, essentially all red cells lysed | 91.8% | Acceptable |
| Correlation (CD19 R-PE vs. Coulter CD19 RD1, n=175) | High r^2 value and similar percentages | Mean % positive Caltag: 16.4%, Coulter: 16.2%; r^2: 97.7, slope: 0.92 | Substantially equivalent |
| Correlation (CD19 R-PE vs. Coulter CD19 FITC, n=175) | High r^2 value and similar percentages | Mean % positive Caltag: 16.4%, Coulter: 16.7%; r^2: 96.3, slope: 0.93 | Substantially equivalent |
| Correlation (CD19 TRI-COLOR vs. Coulter CD19 RD1, n=175) | High r^2 value and similar percentages | Mean % positive Caltag: 17.1%, Coulter: 16.2%; r^2: 96.7, slope: 0.92 | Substantially equivalent |
| Correlation (CD19 TRI-COLOR vs. Coulter CD19 FITC, n=175) | High r^2 value and similar percentages | Mean % positive Caltag: 17.1%, Coulter: 16.7%; r^2: 97.4, slope: 0.94 | Substantially equivalent |
| Correlation (CD19 TRI-COLOR vs. Caltag CD19 R-PE, n=175) | High r^2 value and similar percentages | Mean % positive Caltag: 17.1%, Caltag: 16.4%; r^2: 97.6, slope: 0.99 | Substantially equivalent |
2. Sample size used for the test set and the data provenance
- Expected Value Data: 155 apparently healthy adult normal donors (age 16-72, mean 41).
- Provenance: Geographically diverse areas of the United States, including Western, Eastern, and SouthCentral regions. Included Caucasians, Blacks, Orientals, Hispanics.
- Retrospective/Prospective: Prospective (samples were "collected" and "analyzed" as part of the study).
- Specificity Data: Blood samples from healthy normal donors of Caucasian, Black, Hispanic, and Oriental ethnic origins. The exact number of donors for specificity is not explicitly stated, but it refers back to "each donor" from the expected value pool.
- Provenance: As above, diverse ethnic origins.
- Leukocyte Recovery Data: 5 normal donors (Caucasian, Black, Hispanic, Oriental).
- Provenance: Diverse ethnic origins.
- Red Blood Cell Lysis Data: 5 normal donors.
- Provenance: Not explicitly stated but likely the same pool as the recovery data.
- Correlation Data:
- Normal Donors: 155 normal donor samples.
- Abnormal Donors: 20 abnormal donors.
- Total for Correlation Studies: 175 donors (155 normal + 20 abnormal).
- Provenance: Geographically diverse areas of the United States (Western, Eastern, SouthCentral regions) and diverse ethnic origins (Caucasian, Black, Oriental, Hispanic) for normal donors. Abnormal donor provenance is not specified beyond "a single site."
- Retrospective/Prospective: Prospective (samples were "collected and analyzed").
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This device is a lysing solution and monoclonal antibody, not an AI/ML diagnostic device requiring expert interpretation for ground truth. The "ground truth" here is the established performance of predicate flow cytometry reagents and procedures using standard laboratory quantification (flow cytometers, hematology analyzers).
4. Adjudication method for the test set
Not applicable. See point 3. The measurements are objective counts by laboratory equipment.
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
Not applicable. This is not an AI/ML device involving human readers or interpretation. The study compares the performance of the device (lysing solution with Caltag antibodies) against predicate devices (Coulter antibodies) using flow cytometric analysis.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
The device itself (lysing solution) is a reagent, not an algorithm. Its performance is evaluated in a standalone manner in conjunction with Caltag monoclonal antibodies as part of a flow cytometric procedure, comparing its output to that obtained with predicate antibodies and lysing agents. The "standalone" performance here refers to the measured results from the flow cytometer after using the Caltag Cal-Lyse solution and antibodies, rather than human interpretation of images. The objective measurements (e.g., % positive cells, cell counts) are the direct output being evaluated.
7. The type of ground truth used
The "ground truth" is established by:
- Comparison to predicate devices: The study aims to prove substantial equivalence to existing, legally marketed devices (Coulter CD19 monoclonal antibodies used with their lysing solutions). Their established performance serves as a benchmark.
- Objective laboratory measurements: Quantification using flow cytometers (FACscan or Profile) and appropriate hematology analyzers for cell counts, percent lysed cells, and percent recovered leukocytes.
- Reference Ranges: Expected values are compared to general established ranges for T and B cells in healthy adults, though the study also establishes a range for its own device.
This is primarily a comparative study against a predicate device using objective laboratory measurements rather than pathology or expert consensus on image interpretation.
8. The sample size for the training set
Not applicable. This is not an AI/ML device requiring a training set in the conventional sense. The studies described are for validation of the lysing solution and antibodies, not for training a model.
9. How the ground truth for the training set was established
Not applicable. See point 8.
§ 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.”