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The Alinity i Rubella IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of IgG antibodies to rubella virus in human serum, serum separator, and plasma tubes (lithium heparin, lithium heparin separator, and tripotassium EDTA) on the Alinity i system.

The Alinity i Rubella IgG assay is to be used as an aid in the determination of immune status to rubella in individuals including women of child-bearing age.

The Alinity i Rubella IgG assay has not been cleared for use in screening blood, plasma, or tissue donors.

The performance of this device has not been established for cord blood or neonatal samples. Likewise, performance has not been established for populations of immunocompromised or immunosuppressed individuals.

The Alinity i Rubella IgG assay is an automated, two-step immunoassay for the quantitative determination of anti-rubella IgG in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology.

Sample, partially purified rubella virus-coated paramagnetic microparticles, and assay diluent are combined and incubated. The anti-rubella IgG present in the sample bind to the rubella virus coated microparticles. The mixture is washed. Anti-human IgG acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added.

The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a direct relationship between the amount of anti-rubella IgG in the sample and the RLU detected by the system optics.

Here's an analysis of the acceptance criteria and the study proving the device meets those criteria, based on the provided FDA 510(k) clearance letter for the Alinity i Rubella IgG assay.

Overview of the Device and its Purpose:

The Alinity i Rubella IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of IgG antibodies to the rubella virus. It's intended to aid in determining the immune status to rubella, particularly in women of child-bearing age. It is a diagnostic device, not an AI/ML-driven one, so some of the requested points regarding AI/ML studies (like MRMC studies, training set details, expert ground truth establishment for AI) are not applicable.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a diagnostic assay and not an AI/ML device, the acceptance criteria are related to the analytical and clinical performance of the immunoassay itself rather than metrics like AUC, sensitivity/specificity for object detection, or F1 scores inherent to AI. The key performance indicators are Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a composite comparator method.

Acceptance Criteria (Implied by Performance Targets in Context of 510(k) Equivalence):

For a 510(k) substantial equivalence determination, the new device must demonstrate performance that is as safe and effective as a legally marketed predicate device. While explicit numerical acceptance criteria for PPA and NPA are not stated in the summary, typical expectations for diagnostic assays like this are high agreement rates (e.g., >90% or 95%) with the comparator method, especially in categories such as "Reactive" and "Nonreactive." The confidence intervals should also demonstrate a reasonable level of certainty around these agreement rates. The acceptance of the listed performance values below implies that these meet the FDA's criteria for substantial equivalence to the predicate.

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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 can be configured as:

· One stand-alone automated hematology analyzer system.

· A multimodule system that includes at least one Alinity hg 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, LYM, %M, EOS, %E, BASO, %B, IG, %IG, RBC, HCT, HGB, MCV, MCH, MCHC, MCHr, RDW, NRBC, NR/W, RETIC, %R, IRF, PLT, MPV, %rP. The Almity 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 Alinity hq is a quantitative, multi-parameter, automated hematology analyzer designed for in vitro diagnostic use in counting and characterizing blood cells using a multi-angle polarized scattered separation (MAPSS) method to detect and count red blood cells (RBC), nucleated red blood cells (NRBC), platelets (PLT), and white blood cells (WBC), and to perform WBC differentials (DIFF) in whole blood.

There is also an option to choose whether to detect reticulocytes (RETIC) at the same time. The options of the selections are:

• CBC+DIFF: Complete blood count with differential
• CBC+DIFF+RETIC: Complete blood count with differential and reticulocyte ●

The Alinity h-series of instruments has a scalable design to provide full integration of multiple automated hematology analyzers that can include the integration of an automated blood film preparation and staining module, all of which are controlled by one user interface. 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).

An Alinity h-series system can be configured as follows:

• Configuration 1: 1 (Alinity hq) + 0 (Alinity hs) = 1+0
• . Configuration 2: 1 (Alinity hq) + 1 (Alinity hs) = 1+1
• . Configuration 3: 2 (Alinity hq) + 0 (Alinity hs) = 2+0
• . Configuration 4: 2 (Alinity hq) + 1 (Alinity hs) = 2+1

Here's a breakdown of the acceptance criteria and study information for the Alinity h-series System, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state all acceptance criteria in a dedicated table format with clear "criteria" vs. "performance" columns for every test. However, it does mention that all results "met the predefined acceptance criteria" for various tests. The tables provided show the device's performance, and the accompanying text confirms it met criteria.

Here's a consolidated view of relevant performance data presented, with implicit acceptance criteria being that the results are within acceptable ranges for clinical diagnostic instruments, or that they demonstrate improvement as intended by the software modification.

2. Sample Size Used for the Test Set and Data Provenance

The "test set" for this submission largely refers to re-analyzing raw data from the predicate device's (K220031) submission using the new algorithm.

• For Precision Studies (Normal Samples):
  • Sample Size: 20 unique healthy donors for CBC+Diff, 19 for CBC+Diff+Retic.
  • Data Provenance: Retrospective (raw data files from K220031 submission were replayed). The origin of the donors (country) is not specified, but they are described as "healthy."
• For Precision Studies (Pathological Samples and Medical Decision Levels):
  • Sample Size: Minimum of 16 donors per measurand and range, with a minimum of 4 repeatability samples per measurand and range (2 for CBC+Diff, 2 for CBC+Diff+Retic).
  • Data Provenance: Retrospective (raw data files from K220031 submission were replayed). The origin of the donors (country) is not specified, but they include "abnormal whole blood samples."
• For Linearity:
  • Sample Size: RBC, HGB, NRBC used whole blood samples; WBC, PLT, RETIC used commercially available linearity kits. A minimum of 9 levels were prepared for each measurand.
  • Data Provenance: Retrospective (raw data files from K220031 submission were replayed). Whole blood samples and commercial kits.
• For Method Comparison Study (Subject Device vs. Predicate Device K220031 and Sysmex XN-10):
  • Sample Size: 2,194 unique venous and/or capillary specimens. 1,528 specimens from subjects with medical conditions, 244 without.
  • Data Provenance: Retrospective (raw data files from K220031 submission were replayed). The origin of the donors (country) is not specified, but collected across 7 clinical sites, representing a "wide variety of disease states (clinical conditions)" and "wide range of demographics (age and sex)."
  • Specific "affected samples" for basophil analysis: 67 samples.
• For Specimen Stability Studies:
  • K2EDTA Venous & Capillary Whole Blood: 14 unique native venous, 30 unique native capillary.
  • Controlled Room Temp K2EDTA Venous & Capillary Whole Blood: 10 K2EDTA venous from healthy donors, 10 abnormal de-identified leftover K2EDTA venous, 20 normal K2EDTA capillary.
  • K3EDTA Venous Whole Blood: 14 unique native venous.
  • K3EDTA Capillary Whole Blood: 94 unique native capillary.
  • Data Provenance: Retrospective (raw data files from K220031 submission were replayed). Samples from "apparently healthy donors" and "abnormal de-identified leftover" samples.
• For Detection Limit:
  • Sample Size: 2 unique samples per day over a minimum of 3 days.
  • Data Provenance: Retrospective (raw data files from K220031 submission were replayed).
• For Clinical Sensitivity/Specificity:
  • Sample Size: A subset of 674 venous and capillary whole blood specimens from the method comparison study.
  • Data Provenance: Retrospective (raw data files from K220031 submission were replayed). Collected from 6 clinical sites.
• For Reference Range Verification:
  • Sample Size: Not explicitly stated but implied to be from the K220031 submission's reference range studies using "apparently healthy subjects" for adult and pediatric subgroups.
  • Data Provenance: Retrospective (raw data files from K220031 submission were replayed).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

• Clinical Sensitivity/Specificity Study:
  • Number of Experts: Two independent 200-cell microscopic reviews were performed. So, at least two experts per sample.
  • Qualifications: Not explicitly stated beyond "microscopic reviews of a blood smear (reference method)." It can be inferred these would be qualified laboratory professionals (e.g., medical technologists, clinical laboratory scientists) with expertise in manual differential counting, but specific years of experience or board certifications are not provided.
  • Ground Truth: The "final WBC differential and WBC, RBC, and PLT morphology results were based on the 400-cell WBC differential counts derived from the average of 2 concurring 200-cell differential counts and concordant RBC and PLT morphology results..."

4. Adjudication Method for the Test Set

• Clinical Sensitivity/Specificity Study: The ground truth was based on "the average of 2 concurring 200-cell differential counts and concordant RBC and PLT morphology results." This indicates an agreement-based adjudication method, likely a 2-of-2 consensus. If the two initial reviews did not concur, a third review/adjudication might have been employed (e.g., 2+1), but this is not explicitly stated. The phrasing "concurring 200-cell differential counts" strongly suggests initial agreement was required.

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, an MRMC comparative effectiveness study was not done in the context of human readers improving with AI assistance.
• This submission describes an automated differential cell counter (Alinity h-series System) which is a standalone device for providing results without human assistance in the interpretation of the primary measurements (though human review of flags/smears may occur downstream).
• The study primarily focuses on comparing the output of the device with its new algorithm (SW 5.8) to its previous version (SW 5.0) and to a predicate device (Sysmex XN-10). The clinical sensitivity/specificity study compares the device's algorithmic flags/differentials to microscopic analysis (human experts), but this is not an assistance study but rather a standalone performance evaluation against a gold standard.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

• Yes, a standalone performance evaluation was primarily done. The core of this submission is about a software algorithm modification within an automated analyzer.
• All analytical performance studies (precision, linearity, detection limits, stability) and method comparison studies (against the predicate and Sysmex XN-10) evaluate the Alinity hq (with the new algorithm) as a standalone instrument.
• The clinical sensitivity and specificity study also evaluates the Alinity hq's ability to identify abnormalities and morphological flags independently, comparing its output directly to expert microscopic review (ground truth). There's no mention of a human-in-the-loop scenario where humans are presented with AI results to improve their performance.

7. The Type of Ground Truth Used

• Expert Consensus (Microscopy): For the clinical sensitivity/specificity study, the ground truth for WBC differentials and morphological flags was established by manual microscopic review (400-cell differential) by two independent experts, with results based on their concurrence. This is a form of expert consensus.
• Reference Methods/Device: For analytical performance and method comparison studies, the ground truth was established by:
  • The Alinity hq with its previous software version (K220031) (for direct comparison to the subject device's new software).
  • Another legally marketed predicate device (Sysmex XN-Series (XN-10) Automated Hematology Analyzer K112605).
  • Known concentrations/values in control materials or linearity kits.
  • Clinically accepted laboratory practices and norms (e.g., for precision, stability).

8. The Sample Size for the Training Set

• The document does not provide information on the sample size used for the training set for the algorithm modification. Since this submission describes a modification to an existing algorithm ("modified logic for counting basophils"), it's possible the training was done prior to the original K220031 submission, or that new data was used for a specific refinement without explicit detail in this summary. The focus of this 510(k) is the evaluation of the modified algorithm on existing data and its performance compared to predicates, not the development process of the algorithm itself.

9. How the Ground Truth for the Training Set Was Established

• As the training set details are not provided, the method for establishing its ground truth is also not elaborated upon in this 510(k) summary. Given the nature of a hematology analyzer, it would typically involve meticulously characterized blood samples, often with manual microscopic differentials, flow cytometry reference methods, or other gold standards, aligned with clinical laboratory guidelines.

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The Alkaline Phosphatase assay is used for the quantitation of alkaline phosphatase in human serum or plasma.

Measurements of alkaline phosphatase or its isoenzymes are to be used as an aid in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

The Alkaline Phosphatase assay is an automated clinical chemistry assay.

Alkaline phosphatase in the sample catalyzes the hydrolysis of colorless p-nitrophenyl phosphate (p-NPP) to give p-nitrophenol and inorganic phosphate. At the pH of the assay (alkaline), the p-nitrophenol is in the yellow phenoxide form. The rate of absorbance increase at 404 nm is directly proportional to the alkaline phosphatase activity in the sample. Optimized concentrations of zinc and magnesium ions are present to activate the alkaline phosphatase in the sample.

The FDA document provided is a 510(k) premarket notification for an in vitro diagnostic device, the Alkaline Phosphatase assay. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving safety and effectiveness de novo. Therefore, the information provided relates to testing done to establish equivalence for a pre-existing device with modifications, not a new device.

The study proves that the modified device meets acceptance criteria, primarily by demonstrating that it performs equivalently to the predicate device and that incremental changes do not adversely affect its performance.

Here's an analysis of the acceptance criteria and the study that proves the device meets those criteria, based on the provided text.

Acceptance Criteria and Reported Device Performance

The document provides a general statement that the device "met the pre-defined product requirements for all characteristics evaluated in the verification studies." It doesn't present a specific table of acceptance criteria vs. performance in the typical format of a clinical study, but rather a comparison of characteristics to a predicate device and a statement about the results of verification studies.

The key acceptance criterion discussed is substantial equivalence to the predicate device (K023807), particularly regarding:

• Intended Use and Indications for Use: The subject device is intended for the same use as the predicate: "quantitation of alkaline phosphatase in human serum or plasma," as an aid in diagnosis and treatment of various diseases.
• Methodology and Assay Principle: Both use para-nitrophenyl phosphate and a kinetic measurement method.
• Performance (specifically after IFCC calibration factor change): The 6.5% increase in reported results due to the optional IFCC calibration factor is deemed acceptable because it falls within the acceptable assay bias specifications (up to +/-10%) and the customer would be aware of this change.
• Risk Mitigation: The comprehensive risk-based assessment for all changes ensured that "the accumulated modifications did not impact the performance of the device."

Since this is an in vitro diagnostic device for measuring a specific analyte (Alkaline Phosphatase), the "performance" here refers to analytical performance characteristics rather than clinical diagnostic accuracy in the way a medical imaging AI would.

Here's a table summarizing the implicit acceptance criteria and the reported performance as derived from the document:

Study Details (based on the provided text, which is an FDA clearance letter for an IVD, not a detailed study report for AI/imaging device)

The document relates to modifications made to an existing in vitro diagnostic (IVD) device, not a new AI-powered diagnostic for imaging. Therefore, many of the typical questions for an AI/imaging device (e.g., sample size for test set, expert readers, MRMC study, ground truth for imaging) are not directly applicable or detailed in this type of FDA letter.

However, based on the information provided, we can infer some details relevant to an IVD device:

1. Sample Size used for the test set and the data provenance:

   • Sample Size: Not explicitly stated. The document refers to "verification studies" which typically involve testing samples across the measurement range, parallelism, interference, precision, etc. for an IVD. The exact number of samples (patients or analytical runs) isn't specified in this summary.
   • Data Provenance: Not specified regarding country of origin. The studies are described as "verification studies" and "comprehensive risk-based assessment." For IVDs, these are typically prospective laboratory studies conducted by the manufacturer to validate performance characteristics. It's safe to assume they were laboratory-controlled, likely prospective.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • This question is not applicable in the context of this IVD device. "Ground truth" for an IVD like Alkaline Phosphatase is established by the analytical measurement itself, often compared to reference methods or known concentrations, or through internal validation against established performance claims. It does not involve human expert interpretation of an image or signal.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • This question is not applicable for this IVD. Adjudication methods like 2+1 or 3+1 are used in AI/imaging studies where multiple human readers interpret data that then needs to be reconciled to establish a "ground truth" for comparison with AI. For an IVD, there isn't subjective interpretation of this kind. The measurement process itself generates the result.

4. 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:

   • This type of study is not applicable to this IVD. MRMC studies are specific to AI-assisted imaging diagnostics, evaluating the impact of AI on human reader performance. This device provides a quantitative biochemical measurement, not an image for human interpretation.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • In a sense, yes, the fundamental performance of the IVD is "standalone" in that the automated analyzer (ARCHITECT c System) quantitatively measures alkaline phosphatase activity. The "algorithm" here is the chemical reaction and photometric measurement, and its output is a numerical value (U/L). The verification studies would assess this standalone analytical performance (e.g., precision, accuracy, linearity, detection limits) against pre-defined specifications. The IFCC factor is a mathematical change to this standalone output.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • For an IVD like this, "ground truth" is typically established through:
     • Reference Methods: Comparison of results to established, highly accurate reference methods for alkaline phosphatase.
     • Known Concentrations: Testing samples with precisely known concentrations of alkaline phosphatase.
     • Clinical Correlation: Demonstrating that the assay measures the analyte in patient samples consistently and reliably across relevant patient populations, although the primary ground truth is analytical.
   • The document implies that the "pre-defined product requirements" and "acceptable assay bias specifications" served as the benchmarks for determining if the device performed acceptably. The 6.5% shift from the IFCC factor was evaluated against these analytical specifications.

7. The sample size for the training set:

   • This question is not directly applicable in the context of a traditional IVD chemical assay development, as there isn't an "AI model" that requires a training set in the typical sense. The "training" for such a system would be the chemical formulation and instrument calibration based on extensive R&D and optimization, not a data-driven machine learning process. The "validation" of the final product involves the verification studies mentioned.

8. How the ground truth for the training set was established:

   • As above, not directly applicable. The IVD operates on established biochemical principles. Its "ground truth" for development and optimization would be based on fundamental chemistry, enzyme kinetics, and metrological traceability to international standards (e.g., IFCC reference methods for calibrator values).

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The Alinity i Toxo IgM assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgM antibodies to Toxoplasma gondii in human serum, serum separator, and plasma tubes (lithium heparin, lithium heparin separator, and tripotassium EDTA) on the Alinity i system.

The Alinity i Toxo IgM assay is to be used as an aid in the diagnosis of acute or recent Toxoplasma gondii infection in suspected individuals including women of child-bearing age. It is recommended that the assay be performed in conjunction with a Toxoplasma gondii IgG assay.

The Alinity i Toxo IgM assay has not been cleared for use in screening blood, plasma, or tissue donors.

The Alinity i Toxo IgM assay is an automated, two-step immunoassay for the qualitative detection of IgM antibodies to Toxoplasma gondii in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology. The kit includes Reagents (Microparticles and Conjugate), Calibrator, and Controls.

The provided text is a 510(k) Summary for the Abbott Laboratories Alinity i Toxo IgM assay. It details the device's characteristics, intended use, and performance studies to demonstrate substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided document:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly present a "table of acceptance criteria" with predefined thresholds that the device must meet in a comparative format. Instead, it presents various performance studies (precision, analytical specificity, cross-reactivity, matrix equivalency, class specificity, CDC panel agreement, and clinical agreement) and then summarizes the results of these studies. The implicit acceptance criteria are the successful demonstration of performance comparable to a cleared device and FDA guidance documents.

However, we can infer some "acceptance criteria" from the results presented, especially in the CDC Panel Agreement and Clinical Agreement sections. The document highlights the Percentage Positive Agreement (PPA) and Percentage Negative Agreement (NPA) as key metrics.

Here's a table focusing on the performance of the Alinity i Toxo IgM assay as tested against established benchmarks:

Table of Device Performance Metrics

• Negative Control: SD 0.014 (NAc)
• Positive Control: SD 0.104 (3.8% CV)
• High Nonreactive Panel: SD 0.040 (NAc)
• Low Reactive Panel: SD 0.064 (4.7% CV)
• Reactive Panel: SD 0.109 (4.3% CV)

Reproducibility (5-Day, Multi-Site):

• Negative Control: SD 0.018 (NAc)
• Positive Control: SD 0.132 (5.1% CV)
• High Nonreactive Panel: SD 0.041 (NAc)
• Low Reactive Panel: SD 0.067 (5.1% CV)
• Reactive Panel: SD 0.136 (5.5% CV)
  (Overall low CVs demonstrate good precision.) |
  | Analytical Specificity (Interfering Substances) | No significant interference from common endogenous substances, other conditions, or drugs at specified concentrations. | Endogenous Substances: No significant interference observed for Unconjugated Bilirubin (40 mg/dL), Conjugated Bilirubin (40 mg/dL), Hemoglobin (1000 mg/dL), Total Protein (15 g/dL), Triglycerides (3000 mg/dL).
  Other Conditions: No significant interference observed for HAMA (800 ng/mL), RF (200 IU/mL).
  Drugs: No significant interference observed for Ascorbic Acid (300 mg/L), Atovaquone (120 mg/L), Beta Carotene (6 mg/L), Biotin (4250 ng/mL), Clindamycin (5.1 mg/dL), Folic Acid (100 nmol/L), Pyrimethamine (15 mg/L), Spiramycine (4.2 mg/L), Sulfadiazine (25.5 mg/dL), Sulfamethoxazole (210 mg/dL), Trimethoprim (4.2 mg/dL). |
  | Cross-Reactivity | Minimal false reactive results from individuals with other medical conditions and high titer Toxoplasmosis IgG. | Out of 177 specimens from individuals with various unrelated conditions (e.g., CMV, EBV, HSV, Flu vaccine recipients, Syphilis, etc.) and high titer Toxoplasmosis IgG, only 1 out of 10 RF (Rheumatoid Factor) specimens resulted in a false reactive result. |
  | Matrix Equivalency | Acceptable performance across different blood collection tube types (serum, serum separator, lithium heparin plasma, lithium heparin plasma separator, and tripotassium EDTA plasma). | All tested blood collection tube types were found acceptable for use with the Alinity i Toxo IgM assay. |
  | Class Specificity | Reactivity only to human anti-Toxoplasma IgM and no reactivity to human anti-Toxoplasma IgG. | Demonstrated reactivity only to human anti-Toxoplasma IgM, with no reactivity to human anti-Toxoplasma IgG. |
  | CDC Panel Agreement | High positive and negative percent agreement with the CDC Toxoplasma 1998 Human Serum Panel. | PPA: 100.00% (32/32) with 95% CI (89.28%, 100.00%)
  NPA: 100.00% (65/65) with 95% CI (94.42%, 100.00%) |
  | Clinical Agreement | High positive and negative percent agreement with an FDA-cleared predicate assay. | Population 1 (n=897):
• PPA: 94.94% (150/158) with 95% CI (90.33%, 97.41%)
• NPA: 94.44% (697/738) with 95% CI (92.55%, 95.88%)
  Population 2 (pregnant women, n=234):
• PPA: 94.74% (18/19) with 95% CI (75.36%, 99.06%)
• NPA: 100.00% (215/215) with 95% CI (98.24%, 100.00%) |

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Cutoff Establishment (Internal Validation): 1219 samples (1053 nonreactive, 166 reactive). Data provenance not specified (likely internal laboratory samples, retrospective).
• Within-Laboratory Precision (20-Day): Not directly a "test set" sample size for diagnostic accuracy, but involves 2 controls and 4 plasma panels tested multiple times (360-360 replicates per control/panel).
• Analytical Specificity (Interference): Samples with target ranges of anti-Toxo IgM (0.60 to 0.99 S/CO and 1.00 to 2.00 S/CO) spiked with interferents. Specific number of samples per substance/condition not given, but refers to CLSI guidance.
• Cross-Reactivity: 177 serum specimens from individuals with other medical conditions and high titer Toxoplasmosis IgG. Data provenance not specified (likely retrospective or collected for study).
• Matrix Equivalency: 43 donors (20 reactive, 23 nonreactive). Samples collected in 5 different tube types. Data provenance not specified.
• Class Specificity: Not specified as a separate sample set size, likely inferred from internal controls or prepared samples.
• CDC Panel Agreement: 97 specimens (32 true positive, 65 true negative) from the CDC Toxoplasma 1998 Human Serum Panel. This is a retrospective, well-characterized panel.
• Reproducibility (5-Day, Multi-Site): Same sample panels as within-laboratory precision (controls and 4 plasma panels) tested across 3 US sites. 360 replicates per sample.
• Clinical Agreement:
  • Population 1: 897 consecutively collected remnant specimens. 169 from the US and 710 from outside the US. This implies a mixture of retrospective and potentially prospective collection depending on "consecutively collected remnant specimens."
  • Population 2: 207 consecutively collected remnant specimens from pregnant women in the US. This implies a mixture of retrospective and potentially prospective collection.
  • Total US specimens in the clinical study: 376 (169 from Pop 1 + 207 from Pop 2).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

• The document does not mention the use of experts (e.g., radiologists) for establishing ground truth, as this is an in vitro diagnostic (IVD) device for serological testing.
• Ground Truth for IVDs: For IVDs like this, "ground truth" is typically established by:
  • Reference Method/Predicate Device: The clinical agreement study uses an "FDA-cleared, commercially available anti-Toxo IgM assay" (the bioMérieux VIDAS TOXO IgM assay) as the comparator, which serves as the reference standard for clinical performance.
  • Well-Characterized Panels: The CDC Toxoplasma 1998 Human Serum Panel is used, where the "true positive" and "true negative" status of specimens are established by the CDC through their own rigorous characterization processes.
  • Internal Characterization: For studies like cutoff determination, samples are "characterized with a commercially available anti-Toxo IgM assay," implying the use of an existing reference method.

Therefore, the "experts" in this context are the established reference methods and panels from organizations like the CDC, rather than individual human interpretative experts for modalities like radiology.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

• Adjudication methods like 2+1 or 3+1 are typically used in imaging studies where multiple human readers interpret images, and discrepancies are resolved by an expert panel.
• For an IVD assay like this, the "adjudication" is inherent in the comparison to a predefined reference standard (the predicate device or the CDC panel's established status) or by the assay's internal cutoff determination process.
• The document does not describe any specific human "adjudication" process for the result of the Alinity i Toxo IgM assay beyond its comparison to the comparator assay or CDC 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, an MRMC comparative effectiveness study was not done.
• MRMC studies are specific to AI/CADe (Computer-Assisted Detection) or CADx (Computer-Assisted Diagnosis) devices that assist human readers in interpreting medical images.
• The Alinity i Toxo IgM assay is an in vitro diagnostic (IVD) device that performs a laboratory test for antibodies; it does not involve human readers interpreting images or AI assistance for such interpretation.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

• Yes, this device inherently performs as a standalone "algorithm" in the sense that it is an automated laboratory assay. The results (S/CO values) are generated by the instrument based on its chemical reactions and detection system, and then interpreted against predefined cutoffs.
• While a human operator loads samples and manages the instrument, the diagnostic detection (CMIA technology for Toxo IgM antibodies) is fully automated by the device itself, without human interpretation of the primary result (RLU or S/CO). The physician then interprets the qualitative result (Reactive, Grayzone, Nonreactive) in the context of the patient's clinical picture.
• The performance metrics (precision, analytical specificity, cross-reactivity, CDC panel agreement, clinical agreement) are all measures of this standalone analytical performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for this device was established primarily through:

• Reference Standard/Predicate Assay: For the clinical agreement study, the Alinity i Toxo IgM assay results were compared against an FDA-cleared, commercially available anti-Toxo IgM assay (the bioMérieux VIDAS TOXO IgM assay). This predicate device serves as the clinical "ground truth" or reference.
• Well-Characterized Panel: For the CDC Panel Agreement study, the ground truth was the established status of samples within the CDC Toxoplasma 1998 Human Serum Panel (i.e., known true positive or true negative Toxoplasma specimens). This panel's characterization is highly reliable.
• Internal Characterization/Comparator Assay: For cutoff establishment, samples were characterized using a "commercially available anti-Toxo IgM assay."

8. The sample size for the training set

• The document does not explicitly describe a separate "training set" in the context of machine learning or AI model development.
• For IVD devices, a "training set" might loosely refer to the samples used during assay development and optimization (e.g., for reagent formulation, instrument parameters, and initial cutoff setting), but this data is not typically reported as a formalized "training set" size in the same way as for AI.
• The closest description of data used for internal calibration/optimization is the 1219 samples used for assay cutoff establishment (1053 anti-Toxo IgM nonreactive samples and 166 anti-Toxo IgM reactive samples). This dataset could be considered analogous to a development/training set for establishing the assay's interpretation rules, although it's crucial to understand this isn't an AI/ML context.

9. How the ground truth for the training set was established

• As mentioned above, there isn't a traditional "training set" for an AI model.
• For the 1219 samples used to establish the assay cutoff, the ground truth (reactive/nonreactive) was established by characterizing these samples with a "commercially available anti-Toxo IgM assay." This means the existing, established methods of Toxo IgM detection were used to classify these samples, allowing the Alinity i assay to be "trained" (or its cutoff optimized) to align with those established classifications.

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The TBI test is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays (CMIA) used for the quantitative measurements of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) in human plasma and serum and provides a semi-quantitative interpretation of test results derived from these measurements using the ARCHITECT i1000SR System.

The interpretation of test results is used, in conjunction with other clinical information, to aid in the evaluation of patients, 18 years of age or older, presenting with suspected mild traumatic brain injury (Glasgow Coma Scale score 13-15) within 12 hours of injury, to assist in determining the need for a CT (computed tomography) scan of the head. A negative test result is associated with the absence of acute intracranial lesions visualized on a head CT scan.

The TBI test is intended for use in clinical laboratory settings by healthcare professionals.

The TBI test is a panel of in vitro diagnostic quantitative measurements of GFAP and UCH-L1 and provides a semi-quantitative interpretation of GFAP and UCH-L1 in human plasma and serum.

GFAP: This assay is an automated, two-step immunoassay for the quantitative measurement of GFAP in human plasma and serum using chemiluminescent microparticle immunoassay (CMIA) technology.

UCH-L1: This assay is an automated, two-step immunoassay for the quantitative measurement of UCH-L1 in human plasma and serum using CMIA technology.

Interpretation of Results: The assay cutoffs were established to be 35.0 pg/mL (35.0 ng/L) for GFAP and 400.0 pg/mL (400.0 ng/L) for UCH-L1. The GFAP and UCH-L1 results are reported separately and the software provides a TBI interpretation relative to the respective cutoff values.

The provided text describes the TBI (Traumatic Brain Injury) test, an in vitro diagnostic device, and its performance evaluation for the ARCHITECT i1000SR system. The submission is a 510(k) for substantial equivalence to a predicate device (TBI on the Alinity i system).

Here's an analysis of the acceptance criteria and study as per your request, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document does not explicitly present a "table of acceptance criteria" in the format of specific thresholds for the performance metrics. Instead, it states that the device "met the pre-defined product requirements for all characteristics evaluated in the verification studies." The performance metrics reported are for precision (20-Day and Reproducibility), Limits of Blank (LoB), Detection (LoD), Quantitation (LoQ), and Linearity, along with a comparison summary using Passing-Bablok regression against the predicate device.

Table of Reported Device Performance (Implied Acceptance through Meeting Requirements):

Study Details:

1. Sample sizes used for the test set and the data provenance:

   • Test Set (Method Comparison): N=123 for both GFAP and UCH-L1 assays in the comparison study against the predicate device.
   • Data Provenance: The document does not specify the country of origin of the data or whether the data was retrospective or prospective. It refers to "verification studies" and "studies were performed based on guidance from CLSI EP09c, 3rd ed." These are typically laboratory-based analytical performance studies. The clinical utility of the test (used to aid in evaluation of patients with suspected mild TBI to determine need for CT scan) suggests that patient samples were likely used for the comparison study, but details about their collection (retrospective/prospective, patient demographics, clinical context) are not provided in this summary.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • This information is not applicable and not provided in the document. The TBI test is an in vitro diagnostic (IVD) quantitative measurement of biomarkers (GFAP and UCH-L1). The "ground truth" for its performance is established by comparison to a legally marketed predicate device (K223602, TBI for Alinity i) and internal analytical performance studies using known concentrations or reference methods. The "interpretation of test results" for the TBI test (positive/negative) is based on established cutoff values for GFAP and UCH-L1, which are compared to CT scan results (absence of acute intracranial lesions). There is no mention of human experts directly establishing "ground truth" for the device's output itself in this context.

3. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

   • Not applicable. This is an IVD device measuring biomarkers. Adjudication methods like 2+1 or 3+1 are typically used in image-based diagnostic studies where human readers interpret images, and consensus is sometimes needed to establish ground truth or resolve discrepancies.

4. 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. This is an in vitro diagnostic (IVD) test, not an AI-assisted imaging device that impacts human reader performance. Therefore, an MRMC study and effect size on human readers are not applicable.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

   • Yes, in a sense. The TBI test is a standalone device (a panel of immunoassays interpreted by defined cutoffs). Its performance is evaluated analytically (precision, linearity, LoD/LoQ) and by direct comparison of its measurements to those of a predicate device, which is also a standalone IVD. The interpretation of the test results (positive/negative) is an automated process based on the measured biomarker levels and predefined cutoffs. While the "interpretation of test results is used, in conjunction with other clinical information, to aid in the evaluation of patients... to assist in determining the need for a CT (computed tomography) scan," the device itself provides the result as an algorithm-driven interpretation (based on raw measurement data).

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • For the quantitative measurements (GFAP, UCH-L1), the "ground truth" in the comparative study is the performance of the legally marketed predicate device (TBI on Alinity i system, K223602). Analytical performance metrics (LoB, LoD, LoQ, linearity, precision) are established using reference materials or samples with known or characterized concentrations.
   • For the clinical context of determining the "need for a CT scan of the head," the ground truth stated for a negative test result is its association with "the absence of acute intracranial lesions visualized on a head CT scan." This implies that CT scan findings serve as the clinical ground truth for evaluating the negative predictive value of the test, though this specific performance characteristic is not detailed in the provided summary. For the positive result, the test aids in determining the need for a CT scan, but the summary doesn't explicitly state the ground truth for a positive result (e.g., presence of lesions, clinical outcome).

7. The sample size for the training set:

   • No information about a "training set" is provided. This is an IVD device based on established immunoassay technology and predefined cutoffs, not a machine learning or AI algorithm that typically requires a distinct training phase with labeled data. The cutoffs (35.0 pg/mL for GFAP and 400.0 pg/mL for UCH-L1) are stated as "established," but the method and data used for their establishment are not described in this summary.

8. How the ground truth for the training set was established:

   • Not applicable as no "training set" is mentioned in the context of this 510(k) summary.

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The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMA) used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric (4 through 21 years) serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin separator, dipotassium EDTA, and tripotassium EDTA tubes) from patients with signs and symptoms or at risk for hepatitis A on the Alinity i system.

The HAVAb IgG II assay is used to determine the immune status of individuals to hepatitis A virus (HAV) infection. Warning: This assay has not been cleared for use in screening blood, plasma, or tissue donors. This assay camot be used for the diagnosis of acute HAV infection.

Assay performance characteristics have not been established when the HAVAb IgG II assay is used in conjunction with other hepatitis assays.

The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric (4 through 21 years) serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin separator, dipotassium EDTA, and tripotassium EDTA tubes) from patients with signs and symptoms or at risk for hepatitis A on the Alinity i system. The kit includes reagents (Microparticles, Conjugate, Assay Diluent), Calibrator, and Controls. The assay is an automated, two-step immunoassay.

Considering the provided document, the device described is an in vitro diagnostic (IVD) assay (HAVAb IgG II) for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV). The FDA 510(k) summary focuses on establishing substantial equivalence to a predicate device, not on meeting specific acceptance criteria in the context of an AI/ML medical device's performance evaluation against clinical ground truth.

Therefore, many of the requested criteria (like ground truth establishment by experts, adjudication methods, multi-reader multi-case studies, and separate training/test sets with their ground truth establishment) are generally not applicable to the performance claims made for this in vitro diagnostic device in this FDA submission. The document describes analytical and clinical performance studies typical for an IVD, focusing on agreement with a predicate device and reproducibility/precision, rather than predictive performance of an AI model against a complex clinical endpoint established by human experts.

Based on the provided text, here's a breakdown of the information that is applicable and a clear indication where the requested information is not present or relevant to this type of device submission:

1. A table of acceptance criteria and the reported device performance

The document doesn't explicitly state "acceptance criteria" in a table format that would typically be found for an AI/ML model for diagnostic imaging (e.g., target sensitivity/specificity values). Instead, it presents performance data for comparison to a predicate device and for reproducibility. The implicit "acceptance criterion" for a 510(k) is demonstrating "substantial equivalence" to a legally marketed predicate device.

However, we can infer some performance metrics presented as evidence of equivalence:

2. Sample sizes used for the test set and the data provenance

• Clinical Performance Test Set (Agreement with Predicate):

  • Individuals at Increased Risk of HAV Infection: n=250
  • Individuals with Signs and Symptoms of Hepatitis Infection: n=499
  • Pediatric Population: n=105
  • Total for Agreement Study: 250 + 499 + 105 = 854 specimens.
  • Data Provenance: Prospective multi-center study.
    • Increased Risk of HAV: collected in California, Colorado, Florida, Illinois, Massachusetts, North Carolina, and Texas.
    • Signs and Symptoms of Hepatitis: collected in California, Colorado, Florida, Illinois, Massachusetts, and Texas.
    • Pediatric Population: collected in the US (California and Massachusetts) and Belgium.

• Precision/Reproducibility Test Sets:

  • Within-Laboratory Precision: n=80 per sample/control for a representative combination (tested over 20 days, 2 replicates/day). Total tested for this study was 4 reagent/calibrator/instrument combinations.
  • System Reproducibility: n=360 per sample/control (tested at 3 sites, with 4 replicates/run, 2 runs/day, 5 days).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

• Not applicable / Not stated. For this IVD device, the "ground truth" for the clinical performance study was the result produced by the legally marketed predicate device (ARCHITECT HAVAB-G). This is a common practice for 510(k) submissions for IVDs. There were no human experts adjudicating results for the purpose of establishing a "ground truth" beyond what the predicate device determined.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

• Not applicable. As the ground truth was the predicate device's result, no human adjudication method (like 2+1, 3+1) was used or described.

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 an in vitro diagnostic assay, not an imaging AI device intended to assist human readers. Therefore, an MRMC study and evaluation of human reader improvement with AI assistance were not performed.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

• Yes, in spirit. The device (HAVAb IgG II assay) functions as a standalone test; it's an automated immunoassay that generates a qualitative result (Reactive or Nonreactive) without human interpretation in the loop influencing the output beyond sample collection and instrument operation. Its performance was assessed directly against the predicate device's results.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

• The "ground truth" for the clinical performance comparison was the results from a legally marketed predicate device (ARCHITECT HAVAB-G assay). In essence, the performance of the new device was compared to the established performance of the predicate. This is a common form of "truth" in demonstrating substantial equivalence for IVDs.

8. The sample size for the training set

• Not explicitly stated in terms of a "training set" for model development. This is an immunoassay, not an AI/ML model where a distinct training dataset size is typically reported. The document describes analytical verification and clinical performance studies, not model training.

9. How the ground truth for the training set was established

• Not applicable. As this is not an AI/ML device in the sense of a machine learning model requiring a training set with a ground truth established by experts for supervised learning, this information is not provided. The development process for an immunoassay does not involve "training data" in the same way an AI/ML model does.

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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).

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.

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The i-STAT PTP45 cartridge is intended for use in the in vitro quantitative measurement of the extrinsic coagulation pathway when activated by thromboplastin in non-anticoagulated whole blood (venous or capillary), using the i-STAT 1 System. Measurements of prothrombin time are used to aid in the monitoring of patients receiving anticoagulant therapy with coumarin derivatives. The i-STAT PT246 Prothrombin Time test result is reported in seconds and as an International Normalized Ratio (INR). The test is intended for point of care use and is for prescription use only.

The i-STAT 1 System consists of the i-STAT 1 analyzer and the i-STAT cartridges. Other components of the i-STAT 1 System are the Electronic Simulator, the i-STAT 1 Downloader/Recharger and the i-STAT Printer. The i-STAT 1 analyzer is a handheld, in vitro diagnostic analytical device designed to run only i-STAT test cartridges. The system is designed for use by trained medical professionals at the patient point of care or in the clinical laboratory and is for prescription use only.

The i-STAT PTPlus cartridge is a coagulation cartridge for determining the time required for complete activation of the extrinsic coagulation cascade. The cartridge contains electrochemical sensors and test reagents that must be mixed with the sample. The reagents include the reactive ingredient to activate the coagulation cascade as well as electrochemical markers that generate a sensor signal when the cascade is fully activated.

The analysis time of the i-STAT PT2405 cartridge is up to 300 seconds (5 minutes). The sample volume required for the i-STAT PT2105 cartridge is approximately 20 ul of whole blood (venous or capillary) without added anticoagulant. The i-STAT PTplus cartridge is a single-use disposable unit that is self-contained. The test reagents and sample fluids do not contact the instrument or user. All the test steps and fluid movements occur within the cartridge.

The i-STAT 1 System has an internal quality control (internal simulator) and an external quality control (Electronic Simulator). The internal and external simulators are used to check the instrument signal-reading function. In addition to the quality controls within the i-STAT 1 System, liquid quality controls are available as an optional quality control methodology to meet the regulatory compliance requirements applicable to the facility where they are to be used.

The liquid quality controls are the i-STAT PT2008 Control Levels 1 and 2 and can be used for the quality control of the i-STAT PT2005 cartridge. The coagulation controls consist of lyophilized citrated human plasma and calcium chloride fluid for reconstitution.

i-STAT PT2145 Control Level 1 has been formulated to produce a normal prothrombin time. Level 2 has been formulated to produce an extended prothrombin time.

Each level of control is packaged as a box of 5 vials containing 1 mL of lyophilized citrated human plasma and 5 vials of 1.5 mL of calcium chloride diluent.

The i-STAT PT2"45 controls are intended for use with the i-STAT PTP"46 cartridge on the i-STAT System, and values assigned to these controls may not be commutable with other commercial methods.

Here's an analysis of the provided FDA 510(k) summary for the i-STAT PTplus Cartridge with the i-STAT 1 System, structured to address your request about acceptance criteria and study proof.

Device: i-STAT PTplus Cartridge with the i-STAT 1 System
Device Name: Prothrombin Time Test
Regulation Number: 21 CFR 864.7750
Regulatory Class: Class II

This document is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device, rather than defining specific pre-defined acceptance criteria in the same way one might for a novel high-risk device or an AI/ML product where clinical endpoints are primary. For an IVD like a PT test, the "acceptance criteria" are generally established through analytical performance metrics that demonstrate equivalence or non-inferiority to a legally marketed predicate and established scientific principles for laboratory tests. The studies predominantly prove analytical performance.

1. Table of Acceptance Criteria and Reported Device Performance

Given this is a 510(k) for an In Vitro Diagnostic (IVD) device, the "acceptance criteria" aren't explicitly stated as pass/fail thresholds against specific performance numbers in the summary. Instead, they are implicitly defined by robust analytical performance demonstrating precision, linearity, traceability, and method comparison with a predicate and a reference method. The goal is to show the new device performs comparably and acceptably for its intended use.

Here, I've interpreted "acceptance criteria" as ranges or levels of performance that are considered acceptable for a prothrombin time test, and then listed the reported device performance.

2. Sample Size Used for the Test Set and Data Provenance

• Precision/Reproducibility (Liquid Controls): N=104-120 per fluid level per cartridge lot (total of 9 measurements * ~115 samples = ~1035 data points). Data provenance implied as internal laboratory study.
• Precision (Whole Blood):
  • Capillary: N=58 (non-therapeutic), N=119 (therapeutic), N=9 (very high therapeutic).
  • Venous: N=65 (non-therapeutic), N=131 (therapeutic), N=13 (very high therapeutic).
  • Data provenance: Samples collected from "three (3) point of care sites" for repeatability analysis. Implied retrospective or prospective collection based on CLSI guidelines.
• Method Comparison (vs. Predicate):
  • Venous: N=191* (samples with outliers included)
  • Capillary: N=153* (samples with outliers included)
  • Data provenance: "prospectively collected from subjects undergoing anticoagulant therapy with coumarin derivates and from subjects who were not on anticoagulant therapy at three (3) clinical sites." (Prospective)
• Method Comparison (vs. Reference):
  • Venous: N=211* (samples with outliers included)
  • Capillary: N=203* (samples with outliers included)
  • Data provenance: "prospectively collected from subjects undergoing anticoagulant therapy with coumarin derivates and from subjects who were not on anticoagulant therapy at three (3) clinical sites." (Prospective)
• Interference: Not explicitly stated N, but implied adequate for the substances tested.
• Factor Sensitivity: Not explicitly stated N.
• Fibrinogen, Platelet, Hematocrit, Heparin Sensitivity, Lupus Anticoagulant: Not explicitly stated N.
• Reference Range:
  • Capillary: N=146
  • Venous: N=154
  • Data provenance: "apparently healthy adult subjects" from "three (3) clinical sites." (Likely Prospective)

Country of Origin: Not explicitly stated, but "CLSI guidelines" are US-based and "FDA" approval implies US studies or studies compliant with US standards. Assuming US/North American origin.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

This section is not applicable in the context of this device. This is an In Vitro Diagnostic (IVD) device for measuring a quantitative biomarker (prothrombin time). The "ground truth" for these studies is typically established by:

• Reference Methods: Such as the Sysmex CS-2500 instrument in this case, which is a laboratory instrument considered a more definitive measurement.
• Predicate Devices: The CoaguChek® XS Plus System, which is a legally marketed device used for comparison to demonstrate equivalence.
• Assigned Values for Controls/Calibrators: For analytical precision and linearity.
• Clinical Outcomes/Pathology: Not used directly for establishing "ground truth" for the PT measurement itself, but the PT values might be correlated with outcomes in broader clinical studies (which are not detailed here as part of the 510k).

There are no human "experts" rating images or making diagnoses that would require adjudication; the measurements are quantitative.

4. Adjudication Method for the Test Set

Not applicable. As a quantitative IVD, there is no subjective rating or interpretation by multiple readers that would require an adjudication method (like 2+1, 3+1 consensus for imaging studies). Measurements from instruments are taken as-is for statistical analysis.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not applicable. This is an In Vitro Diagnostic (IVD) device, not an AI/ML imaging device that assists human readers. Therefore, an MRMC study and analysis of human reader improvement with AI assistance are not relevant to this submission.

6. Standalone (Algorithm Only) Performance

The device itself (i-STAT PTplus Cartridge with the i-STAT 1 System) is the "standalone" diagnostic method. Its performance is measured directly by comparing its results to a predicate device and a laboratory reference instrument (Sysmex CS-2500). There isn't a separate "algorithm" that generates interpretations for human-in-the-loop use. The reported analytical performance (precision, correlation, etc.) reflects its standalone performance.

7. The Type of Ground Truth Used

The ground truth for evaluating the i-STAT PTplus cartridge performance was established primarily through:

• Validated Reference Method: The Sysmex CS-2500 (using Dade Innovin reagent) for venous plasma measurements, considered a reliable laboratory method for PT.
• Legally Marketed Predicate Device: The CoaguChek® XS Plus System, used for direct comparison to demonstrate substantial equivalence.
• Internal Control Fluids/Levels: For precision studies against known or assigned values.
• Clinical Samples: From patients on and not on anticoagulant therapy, characterized by their clinical status.

8. The Sample Size for the Training Set

Not applicable. This device does not use machine learning or AI that requires a "training set" in the traditional sense. It's a chemical and electrochemical analysis system. The development and internal validation of the cartridge's reagents and measurement principles would involve extensive R&D and analytical testing, but this isn't structured as a conventional ML training set.

9. How the Ground Truth for the Training Set Was Established

Not applicable. As stated above, there is no AI/ML training set for this device. The "ground truth" for development and validation would involve standard analytical chemistry and medical device engineering practices, using reference materials, spiked samples, and clinical samples analyzed by established laboratory methods.

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GLP systems Track:

The GLP systems Track is a modular laboratory automation system designed to automate pre-analytical and post-analytical processing, including sample handling, in order to automate sample processing in clinical laboratories. The system consolidates multiple analytical instruments into a unified workflow.

Alinity i Total β-hCG Reagent Kit:

The Alinity i Total β-hCG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative and qualitative determination of beta-human chorionic gonadotropin (ß-hCG) in human serum and plasma for the early detection of pregnancy on the Alinity i analyzer.

Alinity i system:

The Alinity i System is a fully automated analyzer allowing random and continuous access, as well as priority and automated retest processing using chemiluminescent microparticle immunoassay (CMIA) technology is used to determine the presence of antibodies, and analytes in samples.

Alinity ci-series:

The Alinity ci-series is intended for in vitro diagnostic use only.

The Alinity ci-series is a System comprised of inity i or Alinity c analyzers/processing modules that may be arranged into individual or multimodule configurations including up to four Alinity i processing modules, up to four Almity c processing modules, or a combination of up to four of Alinity c processing modules with a shared system control module to form a single workstation.

The Alinity c System is a fully automated, random/continuous access, climical chemistry analyzer intended for the in vitro determination of analytes in body fluids.

The Alinity i System is a fully automated analyzer allowing random and continuous access, as well as priority and automated retest processing using chemiluminescent microparticle immunoassay (CMIA) technology is used to determine the presence of antibodies, and analytes in samples.

The GLP systems Track is a modular laboratory automation system (LAS) used to perform multiple pre-analytical and post-analytical steps to automate sample preparation and distribution processes in clinical laboratories. These processes include bar code identification of samples, centrifugation, aliquoting of samples, decapping of samples, transport of samples between processes (modules), delivery of samples to 1 or more Abbott and Third Party commercially available laboratory analyzer(s), capping of samples, and storage of samples. Due to the modular nature of the LAS, customers may select modules and configurations to fit their laboratory needs.

The provided text describes the 510(k) premarket notification for the GLP systems Track and the Alinity i Total β-hCG Reagent Kit. The focus of the acceptance criteria and study detailed in the document is on the GLP systems Track laboratory automation system, and its ability to maintain the performance of connected analyzers, specifically exemplified with the Alinity i Total β-hCG assay. The document does not provide specific acceptance criteria or performance data for the Alinity i Total β-hCG Reagent Kit as a standalone diagnostic assay; instead, it focuses on the GLP systems Track's compatibility and non-inferiority when integrated with such assays.

Here's a breakdown of the information based on your request:

Acceptance Criteria and Reported Device Performance

The document describes a method comparison study to demonstrate that the GLP systems Track does not negatively impact the performance of connected assays. The acceptance criteria are implicitly defined by the results of this method comparison.

Table of Acceptance Criteria and Reported Device Performance (Implicit for the GLP systems Track):

* **Slope:** 0.99
* **Correlation Coefficient:** 1.00                                                                                                                                                                       |

| Ensure acceptable performance for a representative immunoassay. | Demonstrated with the Alinity i Total β-hCG assay. |

Study Details

1. Sample Size Used for the Test Set and Data Provenance:

   • Sample Size: Not explicitly stated as a number of samples. The range of mIU/mL for the tested samples is given as 4.78 to 14,965.80 mIU/mL, indicating a broad range of concentrations were tested.
   • Data Provenance: The study was described as "Nonclinical testing was performed on-site at Abbott." This indicates an internal, prospective study. Country of origin is implicitly the US, where Abbott Laboratories is located.

2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

   • Not applicable. This was a method comparison study for a laboratory automation system, not a diagnostic study requiring human expert interpretation of results to establish ground truth. The "ground truth" was established by comparing direct loading (comparator method) to processing via the GLP systems Track (investigational method) using established laboratory procedures.

3. Adjudication Method for the Test Set:

   • Not applicable. As this was a method comparison of automated systems, there was no human adjudication process involved. The comparison was based on quantitative measurements.

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

   • No. An MRMC study is typically for image-based diagnostic aids where human readers interpret cases. This study focused on the performance of a laboratory automation system.

5. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:

   • Yes, in essence. The study assessed the performance of the GLP systems Track (an automated system) without human intervention in the analytical process, demonstrating its ability to deliver results comparable to direct sample loading. The Alinity i Total β-hCG assay itself is a standalone quantitative assay.

6. The Type of Ground Truth Used:

   • Reference Method Comparison/Comparator Method. The "ground truth" was established by testing specimens on the Alinity i Total β-hCG assay when front-loaded (the comparator method/reference) and comparing those results to specimens loaded using the GLP systems Track (investigational method). This essentially assumes that the front-loaded method provides the accurate measurement.

7. The Sample Size for the Training Set:

   • Not applicable. The GLP systems Track is a mechanical/software automation system designed for sample processing, not an algorithm that undergoes "training" with data in the typical machine learning sense to learn patterns or make predictions. Its "training" would be through engineering design, development, and testing processes. The document does not mention any machine learning or AI components that would require a training set.

8. How the Ground Truth for the Training Set was Established:

   • Not applicable. (See point 7).

In summary, the provided document focuses on demonstrating the substantial equivalence of the GLP systems Track to its predicate and its ability to integrate with and maintain the performance of an existing cleared assay (Alinity i Total β-hCG) through a nonclinical method comparison study.

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