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Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636 is intended for use in the qualititative detection of human progesterone receptor in tissue sections of human breast cancer by immunohistochemistry. The assay is intended for use as an aid in selecting patients most likely to benefit from hormonal therapy as well as an aid in the prognosis and management of breast cancer.

1. Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, (Product Code No. M3569) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant. The antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, containing fetal bovine serum and 15mM sodium azide. (0.2 mL and 1 mL total volume).

2. Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use Antibody (Product Code No. N1630) consists of a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and pre-diluted in 0.05M Tris-HCl buffer, pH 7.6, containing fetal bovine serum and 15mM sodium azide (7mL and 11 mL sizes).

3. Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use Antibody (Product Code No. NP008) consists of a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and pre-diluted in 0.05M Tris-HCl buffer, pH 7.6, containing fetal bovine serum and 15mM sodium azide (7mL total volume).

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

Device: DAKO Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636 (M3569, N1630, NP008)

Intended Use: Qualitative detection of human progesterone receptor (PgR) in tissue sections of human breast cancer by immunohistochemistry. Aid in selecting patients most likely to benefit from hormonal therapy and in the prognosis and management of breast cancer.

1. Table of Acceptance Criteria and Reported Device Performance:

Note: The document explicitly states the "Concordance calculation showed concordance = 88 / 97 = 90.7% in this trial. Using the PR-ElA as the predicate device, sensitivity was determined to be 41/47 = 87.2% while specificity was determined to be 47/50, = 94%. The Kappa statistic indicated a 0.8139 kappa, which corresponds to an almost perfect correlation for the qualitative assessment." These values are direct performance metrics against the predicate. The criteria are indirectly inferred as the targets needed to demonstrate substantial equivalence.

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

• Sample Size for Comparison Study: 97 breast carcinoma specimens were successfully evaluated for comparison with the Abbott PR-EIA. (Initially, 106 tests were performed on 101 specimens, but 2 had too little tumor tissue and 2 lacked corresponding PR-EIA results, reducing the comparison set to 97).
• Data Provenance: Not explicitly stated, but it's a comparison to the Abbott PR-EIA which is a predicate device, likely indicating retrospective use of existing archived samples with known PR-EIA results. The country of origin is not specified, but given DAKO's location (USA) and the FDA submission, it's reasonable to assume the data is from the US or a region with comparable standards.

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

• Not explicitly stated for the comparison study. The ground truth for the comparison study was established by the Abbott PR-EIA, which is itself a laboratory assay. Therefore, the "ground truth" for this specific comparison was the result generated by the predicate device, rather than a panel of human experts reviewing the slides.
• For the immunohistochemistry (IHC) on normal and tumor tissues, the evaluation of staining patterns and intensities ("3+ staining intensity," "2+ staining intensity") would have been performed by qualified pathologists or laboratory personnel with expertise in IHC interpretation. However, the exact number and qualifications are not mentioned.

4. Adjudication Method for the Test Set:

• Not applicable in the context of the comparison study, as the ground truth was the result from the predicate Abbott PR-EIA assay. The DAKO device's result was compared directly against this predicate result.
• For the initial normal and tumor tissue reactivity studies, the evaluation of staining was reported as findings. There is no mention of an adjudication process (e.g., 2+1, 3+1) for interpreting IHC results in the document; typically, this would be handled by a single qualified individual or through internal quality control mechanisms.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement:

• No, an MRMC comparative effectiveness study was not done. The study presented is a direct comparison of the DAKO device's output against a predicate device's output (Abbott PR-EIA) on breast cancer specimens. It does not involve human readers' interpretation with and without AI assistance to measure improvement.

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

• This device is an antibody reagent for immunohistochemistry (IHC). IHC is inherently a "standalone" assay in the sense that the antibody binds to the target protein in the tissue, and the staining is then visually interpreted.
• The "performance" described here is the ability of this antibody to produce staining results that correlate with a predicate assay for progesterone receptor. There is no "algorithm" or "AI" involved, nor is there a "human-in-the-loop" component beyond the standard interpretation of an IHC slide by a pathologist. This is a traditional IVD reagent, not an AI-powered diagnostic device.

7. The Type of Ground Truth Used:

• For the comparison study: The ground truth was results from the predicate device, Abbott PR-EIA.
• For the normal and tumor tissue reactivity studies: The ground truth was based on expected biological expression of progesterone receptor in various normal and tumor tissues, evaluated by presumably qualified laboratory personnel/pathologists through visual interpretation of IHC staining.

8. The Sample Size for the Training Set:

• Not applicable / not provided. This is an antibody reagent, not a machine learning algorithm. Therefore, there is no "training set" in the computational sense. The antibody's specificity and reactivity are inherent to its molecular properties and laboratory development, not trained on data.

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

• Not applicable. As stated above, there is no training set for this type of device. The development of the antibody (Clone PgR 636) and confirmation of its binding characteristics (e.g., in Western blot described) are part of its development, but not "training" in the context of an AI/ML algorithm.

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Monoclonal Mouse Anti-Human Estrogen Receptor, Clone 1D5 may be used in the semi-quantitative detection of human estrogen receptor in tissue sections of human breast cancer by immunohistochemistry. The information gained by this assay can aid in assessing the likelihood of response to therapy as well as in the prognosis and management of breast cancer patients.

The clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual having knowledge of all the potential antibody reactivities.

1. Monoclonal Mouse Anti-Human Estrogen Receptor, Clone 1D5, Device Code No. M7047) is a mouse anti-human monoclonal antibody (Product) produced as a tissue culture supernatant. The antibody is supplied in Description: 0.05M Tris-HCl buffer, pH 7.2, containing fotal bovine serum and 15mM sodium azide. (1mL total volume).

2. Monoclonal Mouse Anti-Human Estrogen Receptor. Clone 105 Ready-to-Use Antibody and Negative Control (Product Code No. N1576) consists of a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and pre-diluted in 0.05M Tris-HCI buffer, pH 7.6, containing fotal bovine serum and 15mM sodium azide (7mL total volume). The primary antibody is packaged with a negative control reagent consisting of a cocktail of purified mouse immunoglobulins (IgG, IgG, IgGz, IgGz, IgGz and IgM) in 0.05M Tris-HCI buffer, pH 7.6 and 15mM sodium azide (5mL total volume).

The provided text describes DAKO's Monoclonal Mouse Anti-Human Estrogen Receptor, Clone 1D5 (anti-ER, 1D5) and its comparison to a predicate device, Abbott ER-ICA Monoclonal, clone H222. The studies performed focused on demonstrating substantial equivalence, rather than establishing specific quantitative acceptance criteria for the anti-ER, 1D5 device alone against predefined thresholds.

However, based on the comparative effectiveness studies presented, we can infer performance and the methods used to demonstrate the device's utility.

Here's an analysis based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state quantitative "acceptance criteria" for the anti-ER, 1D5 antibody against a specific clinical outcome. Instead, it demonstrates performance by comparing it to an already approved predicate device (Abbott ER-ICA H222) and by citing published studies on its use. The primary goal was to establish substantial equivalence.

The table below summarizes the reported performance of anti-ER, 1D5 and its comparison to the predicate device and clinical outcomes, where available.

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

The "test set" here refers to the various studies cited in the submission for comparative effectiveness and clinical utility. There isn't a single "test set" but rather a collection of published research:

• Normal Tissue Testing: A "required panel of normal tissues" as specified by FDA guidance. The exact number is not explicitly stated in the summary but indicates a prospective testing approach.
• Reproducibility Testing: Eight serial sections from each of three different paraffin-embedded blocks of human breast carcinoma. This was an internal prospective study.
• Comparative Effectiveness and Clinical Utility Studies (Table 1): This table summarizes findings from various published articles.
  • Mauri, et al.: 374 samples.
  • Goulding, et al.: 90 samples.
  • Nedergaard et al.: 83 samples.
  • Pertschuk et al.: 74 samples (all had Stage IV disease; included White, AfroAm, Hispanic, Asian demographics).
  • Leong and Milos.: 31 samples.
  • Pellicer and Sundblad: 300 patients with 5-year follow-up.
  • Hopkins et al.: 51 samples.
  • Hendricks and Wilkinson: 20 samples.

Data Provenance for Published Studies: The text does not explicitly state the country of origin for each study, but given the journal names and author affiliations typically found in such publications, it's highly likely to be a mix of international (including US and European) retrospective cohort studies. The studies are consistently referred to as "Published Immunoreactivity."

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

The text does not specify the number or qualifications of experts used to establish ground truth for the test set utilized in the submission. The studies cited (Table 1) often compare the anti-ER, 1D5 results to the predicate device (H222) or to clinical outcomes like response to tamoxifen.

• In the case of comparison to H222 (predicate device), the ground truth for H222 results would have been established by trained pathologists.
• For clinical outcome data (e.g., tamoxifen response, survival), the ground truth is derived from patient medical records and follow-up data, generally managed and interpreted by clinicians.
• The scoring systems mentioned (e.g., percentage of stained tumor nuclei, H scores, 0-3+ intensity) imply evaluation by trained individuals, likely pathologists, but their number and specific qualifications are not detailed in this summary.

4. Adjudication Method for the Test Set

The submission does not explicitly describe an adjudication method (like 2+1 or 3+1) for the test set examples presented. The performance metrics are reported from individual published studies, which would have had their own internal methods for slide interpretation and data analysis. These methods often involve interpretation by one or more pathologists, but explicit adjudication rules are not provided in this summary.

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 done involving AI assistance. This submission describes an antibody for immunohistochemical staining, not an AI-powered diagnostic device. The comparisons are between two different antibodies (DAKO's 1D5 and Abbott's H222) and their correlation with clinical outcomes.

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

No, a standalone (algorithm-only) performance study was not conducted. This is not an AI device. The device is a diagnostic reagent (antibody) that is interpreted by human observers (pathologists) under a light microscope. The text mentions "image analysis systems" and "automated stainers" as being used in efforts for greater objectivity but notes they "have yet to be validated in the literature," implying they are not part of the core performance claims for this specific 510(k) submission.

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

The ground truth used across the various studies cited is a combination of:

• Pathology: Evaluation of tissue sections by pathologists for the presence and quantity of estrogen receptor staining (both for the predicate device H222 and for anti-ER, 1D5). This includes semiquantitative scoring systems (e.g., percentage of positive cells, staining intensity, H scores).
• Clinical Outcomes Data: Patient follow-up data related to response to therapy (e.g., tamoxifen), overall survival, and relapse-free survival.
• Expert Consensus (Implicit): While not explicitly stated as a formal "expert consensus" process for establishing ground truth within the context of the submission's own testing, the predicate device (Abbott ER-ICA H222) had previously been approved by the FDA based on its established utility and, presumably, expert agreement on its diagnostic accuracy. The studies comparing anti-ER, 1D5 to H222 are effectively using H222 results (interpreted by pathologists) as a reference.

8. The Sample Size for the Training Set

The concept of a "training set" is not applicable in the context of this device, as it is not an AI/machine learning algorithm. The studies described are for validation and comparison of a biological reagent (antibody).

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

As this is not an AI/machine learning device, there is no "training set" for which ground truth would be established. The information gathered about the antibody's characteristics and performance came from its development, internal testing, and independent published research.

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For In Vitro Diagnostic Use

Monoclonal Mouse Anti-Human T-cell, CD3/RPE-Cy5 conjugated, Clone UCHT1 (Code No.C7067) (Anti-CD3/RPE-Cy5) and Monoclonal Mouse Anti-Human T-cell, CD3/RPE conjugated, Clone UCHT1 (Code No. R0810) (Anti-CD3/RPE) have been developed for use in flow cytometry for the analysis of T-cells in peripheral blood. These reagents allow simultaneous detection and quantification of CD3-positive cells (T-cells) in normal and pathological conditions such as immunodeficiency disorders. Each reagent is one component of the suggested monoclonal antibody (MAb) combinations for routine immunophenotyping of lymphocytes in peripheral blood.

Immunophenotyping of lymphocytes is widely applied for diagnosis of immunodeficiencies. DAKO Anti-CD3/RPE-Cy5 is one of the reagents utilized when performing immunophenotyping of lymphocytes.

Monoclonal Mouse Anti-Human T-cell, CD3, Clone UCHT1, RPE conjugated, has been developed for use in flow cytometry for the analysis of T-cells. This reagent allows simultaneous detection and quantification of CD3-positive cells (T-cells) in normal and pathological conditions such as immunodeficiency disorders. It is one component of the suggested monoclonal antibody (MAb) combinations for routine immunophenotyping of lymphocytes in peripheral blood.

Immunophenotyping of lymphocytes is widely applied for diagnosis of immunodeficiencies. DAKO Anti-CD3/RPE is one of the reagents utilized when performing immunophenotyping of lymphocytes.

Monoclonal Mouse Anti-Human T-cell, CD3/RPE-Cy5 conjugated, Clone UCHT1 (Code No. C7067) and Monoclonal Mouse Anti-Human T-cell, CD3/RPE conjugated, Clone UCHT1 (Code No. R0810) are specific for T-lymphocyte cluster determinants as evaluated by the International Workshop on Human Leukocyte Differentiation Antigens. UCHT1 CD3-specific monoclonal antibody was designated B28 antibody at the Second Workshop (Reinherz, EL, Haynes, BF, Nadler, LM, Bernstein, ID, eds. Leukocyte Typing II, Vol. 2. New York-Berlin-Heidelberg-Tokyo: Springer Verlag, 1986.) Purified monoclonal mouse anti-human CD3 is produced in tissue culture, dialyzed and conjugated with either R-phycoerythrin (RPE) covalently coupled to cyanin 5 (Cy5) or R-phycoerythrin (RPE). One ml (1.0 ml) containing the conjugated antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, 15mM NaN3, 0.1M NaCl, stabilized with 1% stabilzing protein.

Monoclonal Mouse Anti-Human T-cell, CD3/RPE-Cy5-conjugated, C7067, and, Monoclonal Mouse Anti-Human T-cell, CD3/RPE, R0810 are specific for T-lymphocyte cluster determinants as evaluated by the International Workshop on Human Leukocyte Differentiation Antigens. UCHT1 CD3-specific monoclonal antibody was designated B28 antibody at the Second Workshop (Reinherz, EL, Haynes, BF, Nadler, LM, Bernstein, ID, eds. Leukocyte Typing II, Vol. 2. New York-Berlin-Heidelberg-Tokyo: Springer Verlag, 1986.) Purified monoclonal mouse anti-human CD3 is produced in tissue culture, dialyzed and conjugated with R-phycoerythrin (RPE) covalently coupled to cyanin 5 (Cy5), or conjugated with R-phycoerythrin (RPE). One ml (1.0 ml) containing the conjugated antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, 15mM NaNg, 0.1M NaCl, stabilized with 1% carrier protein.

Here's a summary of the acceptance criteria and the studies that prove the device meets these criteria, based on the provided text:

Device: DAKO® Mouse Anti-Human T-cell, CD3/RPE-Cy5, Clone UCHT1 (C7067) and DAKO® Mouse Anti-Human T-cell, CD3/RPE, clone UCHT1 (R0810)

Intended Use: For In Vitro Diagnostic Use in flow cytometry for the analysis of T-cells in peripheral blood, allowing simultaneous detection and quantification of CD3-positive cells (T-cells) in normal and pathological conditions. It is a component of suggested monoclonal antibody combinations for routine immunophenotyping of lymphocytes in peripheral blood.

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Sizes Used for Test Set and Data Provenance

• Linearity Test Set: 5 serial dilutions of a cell line expressing the antigen (JM cells) diluted with a cell line without antigenic sites (Raji cells). Data provenance not specified (likely in-house lab, prospective).
• Reproducibility Test Set: 10 replicates from peripheral blood of "three donors" at three concentrations (high, medium, low). Data provenance not specified (likely in-house lab, prospective).
• Specificity Test Set: 5 apparently healthy adult donors of various races. Data provenance: DAKO Corporation (in-house lab, prospective).
• Predicate Correlation Test Set:
  • Healthy Individuals: 153 normal, apparently healthy individuals.
  • Patient Samples: An unspecified number of samples from "patients with illnesses" were added to the healthy individual data.
  • Total for C7067: 177 samples (150 healthy + 27 patient samples).
  • Total for R0810: 176 samples (150 healthy + 26 patient samples).
  • Data Provenance: Three geographically separate laboratories (likely prospective, multi-site study).

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

The studies described are for the performance characteristics of an in vitro diagnostic reagent (antibody). The "ground truth" in this context is based on the inherent molecular specificity of the antibody and its performance in flow cytometry, rather than expert interpretation of complex images or clinical cases.

• No "experts" in the sense of clinicians or radiologists establishing a diagnostic ground truth were used.
• The ground truth for antigen expression was established by using known cell lines (JM cells for expression, Raji cells for no expression) in the linearity study, and by the established methodology of flow cytometry for reproducibility and specificity.
• The predicate correlation study compares the new reagents to a previously validated predicate, implicitly using the predicate's results as a reference.

4. Adjudication Method for the Test Set

Not applicable. This is not a study requiring adjudication of interpretations (e.g., of images or clinical reports) by human readers. The measurements are quantitative outputs from flow cytometry.

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

No, an MRMC comparative effectiveness study was not done. This device is a reagent for flow cytometry, not an algorithm or system that directly aids human readers in interpretation or diagnosis. The study assessed the reagent's performance against established laboratory standards and a predicate device.

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

Yes, the studies conducted (linearity, reproducibility, specificity, predicate correlation) assess the standalone performance of the reagents themselves in a laboratory setting when used in flow cytometry. While flow cytometry involves human operation, the performance metrics reported are for the reagent's ability to bind to target cells and be quantified, not for human interpretation aided by an algorithm.

7. The Type of Ground Truth Used

• Linearity: Known concentrations of antigen-expressing cells (JM cells) mixed with non-expressing cells (Raji cells).
• Reproducibility: Target population of CD3+ lymphocytes within peripheral blood samples, as measured by flow cytometry. The reference values are the means of the repeated measurements.
• Specificity: Known cell populations (RBCs, granulocytes, monocytes, lymphocytes, platelets) obtained from healthy donors. The expected "ground truth" is that the antibody should primarily bind to lymphocytes (T-cells).
• Predicate Correlation: The results obtained using the legally marketed predicate device (DAKO Mouse anti-human T-cell, CD3/FITC, Clone UCHT1 Code No. F0818) serve as the reference standard.

8. The Sample Size for the Training Set

The provided text does not explicitly mention a "training set" in the context of machine learning or algorithm development. The device is a diagnostic reagent (antibody) for flow cytometry, and its development typically involves laboratory characterization rather than iterative training on large datasets like an AI algorithm. If "training" refers to the development and initial characterization of the antibody itself:

• The antibody (UCHT1) was designated at the "Second Workshop" (International Workshop on Human Leukocyte Differentiation Antigens), implying a historical development and characterization process that predates this submission.
• The production of purified monoclonal mouse anti-human CD3 is described, but the "training set" size for its initial development or characterization is not specified in this document.

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

As noted above, a "training set" in the machine learning sense is not directly applicable here. The "ground truth" for the antibody's properties (specificity to CD3, binding characteristics) would have been established through:

• Immunological assays: Early characterization during antibody development to confirm its binding to the CD3 antigen on T-cells.
• International Workshops: The antibody's designation (B28 antibody at the Second Workshop) indicates that its specificity and reactivity were validated and recognized by the scientific community, likely through extensive testing against various cell types and patient samples, establishing its utility as a marker for CD3. This historical validation forms the basis of its "ground truth" for specificity.

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Mouse IgG1, clone DAK-GO1 Negative Control Reagents are fluorescent conjugated (fluorescein isothiocyanate isomer 1 (FITC), R-Phycoerythrin (RPE), or R-Phycoerythrin-Cyanin 5 (RPE-CY5)) monoclonal antibodies that have been developed for use as negative control reagents for FITC, RPE or RPE-CY5 conjugated monoclonal antibodies of the IgG, heavy chain isotype in preparations of normal whole peripheral blood by flow cytometric methods. Negative control reagents are one component of the suggested controls for monoclonal antibody (MAb) combinations for routine immunophenotyping of lymphocytes in peripheral blood.

Monoclonal Mouse IgG₁, DAK-GO1 FITC, RPE or RPE-CY5 conjugated are directed against Aspergillus niger glucose oxidase, an enzyme that is neither present nor inducible in mammalian tissues. Purified monoclonal mouse IgG1 is produced in tissue culture, dialyzed and conjugated with Fluorescein (FITC), R-phycoerythrin (RPE), or R-phycoerythrin (RPE) covalently coupled to cyanin 5 (Cy5). FITC CONJUGATED: One ml (1.0 ml) containing the conjugated antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, 15mM NaN₃, stabilized with 1% carrier protein. RPE and RPE-Cy5 CONJUGATED: One ml (1.0 ml) containing the conjugated antibody is supplied in 0.05M Tris-HCI buffer, pH 7.2, 15mM NaN₃, 0.1M NaCl stabilized with 1% carrier protein

Here's an analysis of the provided text regarding the DAKO IgG1/FITC, IgG1/RPE, and IgG1/RPE-CY5 devices, focusing on acceptance criteria and supporting studies:

It's important to note that this document is a 510(k) summary submitted to the FDA in 1999 for a diagnostic device. The 'acceptance criteria' and 'device performance' are described in terms of demonstrating substantial equivalence to a predicate device, rather than a quantifiable efficacy for a clinical outcome in the way an AI algorithm might be evaluated today. The performance metrics focus on the analytical characteristics of the reagents as negative controls.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for these negative control reagents are implied through comparability to the predicate device and demonstration of their intended function (non-specific binding in various cell populations and reproducibility). The tables below summarize the reported device performance, which serves as the evidence meeting these implicit acceptance criteria.

Table 1: Reproducibility (Mean % IgG1/Fluorochrome+ Lymphocytes)

Table 2: Specificity (Average % Positive Cells, n=5)

Table 3: Comparison of DAKO IgG1 Reagents vs. Predicate (Gentrak 679.1MC) - Overall

Key Acceptance Criteria (Implicit from provided data and intended use as negative controls):

• Reproducibility: Low variability among replicate samples for measuring non-specificity (<1% positive lymphocytes for FITC/RPE conjugates across donors and platforms). The reported %CV values (e.g., 0.12 - 0.49 for RPE, 0.31 - 0.40 for FITC) demonstrate this.
• Specificity (Lack of specific binding): No significant specific binding to various cell populations (RBCs, granulocytes, monocytes, lymphocytes, platelets). The reported average positive percentages are consistently low, generally below 1%, with the exception of RPE-CY5 binding to monocytes (3.22%) which is addressed by proper gating.
• Substantial Equivalence: Similar performance characteristics (e.g., mean % positive lymphocytes, range, %CV) as the predicate device (Gentrak Genclone mouse IgG₁, 679.1MC) when used as negative controls in flow cytometry. The document shows side-by-side comparison tables.

Study Details:

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

   • Reproducibility: Peripheral blood from 3 donors was used for 10 replicates each (total 30 replicates per fluorochrome-flow cytometer combination). Data provenance is retrospective, from DAKO Corporation (implied, as the manufacturer reports the study). The specific country is not mentioned, but DAKO Corporation is located in Carpinteria, CA, USA.
   • Specificity: 5 apparently healthy adult donors of various races were tested. Data provenance is retrospective, from DAKO Corporation.
   • Correlation/Comparison to Predicate:
     • Initial correlation: 36 apparently healthy individuals at one laboratory.
     • Normal levels of negative events: 150 apparently healthy individuals across three geographically separate laboratories (site 1: n=53, site 2: n=50, site 3: n=50 for DAKO; site 3: n=36 for Gentrak).
   • Provenance: All data appears to be retrospective and collected for the purpose of this 510(k) submission. Country of origin for the studies is implicitly USA, where DAKO Corporation is based.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
   The concept of "ground truth" as it applies to an AI device is not directly applicable here. This is a study of laboratory reagents. The "truth" is established by the inherent characteristics of the reagents (e.g., lack of specific binding to human antigens) as measured by standard laboratory techniques (flow cytometry). The performance metrics (e.g., % positive cells) are direct measurements, not interpretations requiring expert consensus as with image analysis. The results are based on laboratory measurements in apparently healthy individuals.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
   Not applicable. The data being measured (e.g., % positive cells in flow cytometry) are quantitative directly obtained from instrument software, not qualitative assessments requiring adjudication by multiple readers.

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:
   Not applicable. This is not an AI device or a diagnostic device where human reader performance is being evaluated. It is a reagent for laboratory testing.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
   Not applicable. This is not an algorithm-based device. The device itself is the reagent. The "performance" is the analytical performance of the reagent.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
   The "ground truth" in this context is the biological characteristic of the reagents themselves, specifically that they are designed to be negative controls and therefore should exhibit minimal non-specific binding to human leukocyte populations. This is assessed by measuring the percentage of positive cells and the mean channel fluorescence upon exposure to normal human blood samples using established flow cytometry techniques. The "normal" range for negative events is established from a cohort of apparently healthy individuals.

7. The sample size for the training set:
   Not applicable. This is not an AI device that requires a training set. The reagents are manufactured products, and their performance is characterized through laboratory testing.

8. How the ground truth for the training set was established:
   Not applicable, as there is no training set for this type of device.

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Monoclonal Mouse Anti-Human B-cell, CD19, Clone HD37, RPE-Cy5 conjugated, has been developed for use in flow cytometry for the analysis of B-cells. This reagent allows simultaneous detection and quantification of CD19-positive cells (B-cells) in normal and pathological conditions such as immunodeficiency disorders. It is one component of the suggested monoclonal antibody (MAb) combinations for routine immunophenotyping of lymphocytes in peripheral blood.

Immunophenotyping of lymphocytes is widely applied for detection and classification of hematovojetic malignancies, and for diagnosis of immunodeficiencies. DAKO Anti-CD19/Cy5 is one of the reagents utilized when performing immunophenotyping of lymphocytes.

Monoclonal Mouse Anti-Human B-cell, CD19, RPE-Cy5-conjugated, Clone HD37 is specific for B-lymphocyte cluster determinants as evaluated by the International Workshop on Human Leukocyte Differentiation Antigens. HD37 CD19-specific monoclonal antibody was designated B28 antibody at the Second Workshop (Reinherz, EL, Haynes, BF, Nadler, LM, Bernstein, ID, Leukocyte Typing II, Vol. 2. New York-Berlin-Heidelberg-Tokyo: eds. Springer Verlag, 1986.) Purified monoclonal mouse anti-human CD19 is produced in tissue culture, dialyzed and conjugated with R-phycoerythrin (RPE) covalently coupled to cyanin 5 (Cy5). One ml (1,0 ml) containing the conjugated antibody is supplied in 0.05M Tris-HCI buffer, pH 7.2, 15mM NaN3, 0.1M NaCl, stabilized with 1% carrier protein.

This document describes the DAKO® Mouse Anti-Human B-cell, CD19/RPE-Cy5, Clone HD37 (Product Code No. C7066), a monoclonal antibody reagent intended for flow cytometry analysis of B-cells in peripheral blood.

Acceptance Criteria and Device Performance Study Summary

The acceptance criteria for this device are not explicitly stated in a quantitative manner as "acceptance criteria" but are implied through the performance characteristics presented. The study demonstrates the device's linearity, reproducibility, specificity, and correlation with a predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Linearity: 5 dilutions of Raji cells (antigen-positive) diluted with JM cells (antigen-negative). Data provenance is internal (DAKO Corporation, implicitly).
• Reproducibility: 10 replicates from peripheral blood of 3 donors. Data provenance is internal (DAKO Corporation, implicitly).
• Specificity: 5 apparently healthy adult donors of various races. Data provenance is internal (DAKO Corporation, implicitly).
• Predicate Equivalence:
  • 153 normal, apparently healthy individuals. Data provenance: prospective, from three geographically separate laboratories.
  • An additional 27 samples from patients with illnesses. Data provenance: not explicitly stated if prospective or retrospective, but added to the overall dataset for correlation.
  • Total for correlation: 180 samples.

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

The document does not mention the use of experts to establish a "ground truth" in the traditional sense for the performance studies. The measurements (e.g., %CD19+ cells) are direct measurements from flow cytometry, which is an objective measurement technique rather than interpretive.

4. Adjudication Method for the Test Set

Not applicable. The measurements are objective laboratory results and do not require adjudication.

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 device is a monoclonal antibody reagent used in flow cytometry, not an AI or imaging diagnostic tool that involves human "readers" or subjective interpretation.

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

This refers to the performance of the device itself (the antibody reagent) in binding to target cells and being detected by a flow cytometer. The entire testing described (linearity, reproducibility, specificity, predicate comparison) represents the standalone performance of the reagent. Human involvement is in operating the flow cytometer and analyzing the raw data, but the performance metrics directly pertain to the reagent's characteristics.

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

The "ground truth" for the performance studies is rooted in the intrinsic properties of the cells and the flow cytometry method itself:

• Linearity: Based on known concentrations of antigen-expressing cells.
• Reproducibility: Based on repeated measurements of the same samples.
• Specificity: Verified by testing binding to different known cell populations (RBCs, granulocytes, monocytes, lymphocytes, platelets) and observing the expected pattern of strong binding to lymphocytes (B-cells) and minimal binding to others.
• Predicate Equivalence: The predicate device (DAKO Anti-CD19/RPE, HD37 reagent) serves as the "reference standard" or "ground truth" for comparative purposes, implicitly having its own established performance.

8. The sample size for the training set

The document does not mention a "training set" in the context of machine learning or AI algorithms. This device is a biochemical reagent, and its development would typically involve empirical optimization and validation rather than a formal machine learning training phase.

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

Not applicable, as there is no "training set" in the context of the type of device described.

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Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight, clone 34βE12 (34βE12) is intended for laboratory use to qualitatively identify by light microscopy the 66, 57, 51 and 49kD3 proteins corresponding to cytokeratins 1, 5, 10 and 14 of the Moll catalog in acetone or methanol fixed, frozen and formalin, methacarn or Carnoy's fixed, paraffin embedded tissues. 34BE12 specifically binds to antigens located in the cytoplasm of normal squamous and ductal epithelial cells. Positive results aid in the classification of normal and abnormal cells and tissues and serve as an adjunct to conventional histopathology. The clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual.

Anti-Human Cytokeratin. High Molecular Weight, Clone 34BE12 Antibody may be used as one member of a panel of antibodies to aid in the differential diagnosis of anaplastic cells of undetermined origin. When used with markers of simple epithelium, it can aid in the differentiation of carcinomas from non epithelial tumors, e.g., gliomas, lymphomas, melanomas, sarcomas or seminomas. Because it does not react with all carcinomas, it may be used also as an aid in the subclassification of carcinomas. It is also useful in the differential diagnosis of small-acinar lesions of the prostate gland because it stains basal cells which are absent in the disease.

1. Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight, clone 34βE12 (Product Code No. M0630) is a mouse anti-human antibody produced as a tissue culture supernatant. The antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, containing fetal calf serum and 15mM sodium azide. (1mL total volume).
2. Ready-to-Use Monoclonal Mouse Anti-Human Cytokeratin, High Molecular Weight, clone 34βE12 Antibody and Negative Control (Product Code No. N1553) consists of a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and pre-diluted in 0.05M Tris-HCl buffer, pH 7.6, containing fetal calf serum and 15mM sodium azide (7mL total volume). The primary antibody is packaged with a negative control reagent consisting of fetal calf serum in 0.05M Tris-HCl buffer, pH 7.6 and 15mM sodium azide (5mL total volume).

Here's an analysis of the acceptance criteria and supporting study for the DAKO® Mouse Anti-Human Cytokeratin, High Molecular Weight, Clone 34βE12 Monoclonal Antibody (K971905), based on the provided text:

Summary of Acceptance Criteria and Device Performance (Reproducibility Study)

Study Details:

1. Sample Size and Data Provenance for Test Set:

   • Reproducibility Testing: Eight serial sections from each of three different formalin-fixed, paraffin-embedded blocks of normal skin were used. (Total: 24 sections for staining, plus 3 negative control slides per test day).
   • Normal Tissue Testing: A "required panel of normal tissues" was tested. The exact number of tissue samples for each type is not specified but includes 22 different normal tissue types.
   • Data Provenance: The text does not explicitly state the country of origin. The tissues were formalin-fixed and paraffin-embedded, suggesting retrospective collection typical for pathology labs.

2. Number of Experts and Qualifications for Ground Truth (Test Set):

   • The document implies that the "Normal Tissue Testing" and "Reproducibility Testing" were observed and evaluated based on expected staining patterns. It does not explicitly state the number or qualifications of experts who established the ground truth for the test set specifically. However, the "Intended Use" section mentions that "Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified individual," which suggests reliance on general pathology expertise for interpretation of staining results.

3. Adjudication Method for Test Set:

   • "None" explicitly described. The reproducibility section mentions "consistent results," which implies agreement, but no formal adjudication process (e.g., 2+1, 3+1) is detailed. The assessment of normal tissue staining would typically be performed by a single pathologist or a pathology team without a specific adjudication mentioned in the submission.

4. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

   • No MRMC comparative effectiveness study was done or mentioned. This device is a diagnostic reagent (antibody) for immunohistochemistry, not an AI-assisted diagnostic tool for which such studies are typically performed.

5. Standalone Performance (Algorithm Only without Human-in-the-Loop):

   • Not applicable. This device is a monoclonal antibody used in a laboratory setting by trained personnel; it is not an algorithm, and its performance is inherently human-dependent for interpretation.

6. Type of Ground Truth Used:

   • Expected Immunoreactivity/Histological Norms: For normal tissue staining, the ground truth is based on established scientific knowledge of cytokeratin expression in different normal human tissues (i.e., what should stain positive and what should not).
   • Reproducibility Study: The ground truth for reproducibility is the expectation that consistent staining patterns will be observed across repeated tests of the same tissue.
   • Published Immunoreactivity: This section extensively cites published literature (12 articles) to support the understanding of the antibody's reactivity with various normal and neoplastic tissues. This scientific literature serves as a form of expert consensus and outcomes data on cytokeratin expression.

7. Sample Size for Training Set:

   • Not applicable as this is not an AI/machine learning device. The design and validation of the antibody are based on biological and chemical principles, not data-driven training sets in the computational sense.

8. How Ground Truth for Training Set was Established:

   • Not applicable. The "training" for an antibody's performance comes from its biochemical characterization and the vast body of scientific knowledge regarding cytokeratin biology and immunohistochemistry, as summarized in the "Published Immunoreactivity" section and established histological norms.

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Monoclonal mouse anti-human Ki-1 antigen, CD30, Clone Ber-H2 (Ber-H2), may be used as one member of a panel of antibodies to aid in the differential diagnosis of large anaplastic cells of undetermined origin. This antibody stains cell membranes of most cases of anaplastic large cell lymphomas (ALCL), often called Ki-1 lymphomas. It also stains cell membranes and/or cyoplasm of most Hodgkin's lymphomas. Ber-H2 is a valuable aid in the assessment of cutaneous lymphoid infiltrates, particularly when large atypical cells are present. Most nonhomatolymphoid neoplasms are negative with Ber-H2, although there are several significant exceptions. Membrane positivity is seen with embryonal carcinomas, and weak, diffuse cytoplasmic positivity is seen in pancreatic and salivary gland carcinomas.

The staining pattern is most often described as strong membranous and weaker cytoplasmic, specifically paranuclear dot-positivity of the Golgi region. The weak, diffuse cytoplasmic staining is considered to be unexpected, non-specific labeling. It may be reduced or removed by changing the protease pretreatment of the paraffin sections and/or further dilution of the Ber-H2 antibody.

1. Monoclonal Mouse Anti-Human Ki-1 antigen, CD30, Clone Ber-H2 (Product Code No. M0751) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant. The antibody is supplied in 0.05M Tris-HCl buffer, pH 7.2, containing 0.015M sodium azide. (1 ml total volume)

2. Ready To Use Monoclonal Mouse Anti-Human Ki-1 antigen, CD30, Clone Ber-H2 Primary Antibody and Negative Control Reagent (Product Code No. N1558) consists of a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and pre-diluted in 0.05M Tris-HCl buffer, pH 7.6, containing carrier protein and 0.015M sodium azide (7mL total volume). The primary antibody is packaged with a negative control reagent consisting of fetal calf serum in 0.05M Tris-HCl buffer, pH 7.6, containing carrier protein and 0.015M sodium azide (5 ml total volume). The primary antibody and the negative control reagent contain equivalent total protein concentrations.

This document describes the validation study for DAKO Monoclonal Mouse Anti-Human Ki-1 antigen, CD30, Clone Ber-H2 (Product Code No. M0751) and Ready-To-Use Monoclonal Mouse Anti-Human Ki-1 antigen, CD30, Clone Ber-H2 and Negative Control Reagent (Product Code No. N1558).

The device is an in vitro diagnostic intended to qualitatively identify CD30 antigen by light microscopy in acetone-fixed, frozen and formalin or B5-fixed, paraffin-embedded tissues. It is to be used as an aid in classifying normal and abnormal cells and tissues and as an adjunct to conventional histopathology. Specifically, it can aid in the differential diagnosis of large anaplastic cells of undetermined origin, particularly in anaplastic large cell lymphomas (ALCL), Hodgkin's lymphomas, and cutaneous lymphoid infiltrates.

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state "acceptance criteria" in a quantitative, pre-defined manner typical for modern device submissions. Instead, the study aims to demonstrate specific staining patterns and reproducibility as expected for an immunohistochemical antibody. The reported performance is based on descriptive observations of staining in various tissue types and the consistency of these observations.

Note: The submission does not provide quantitative metrics for specificity or sensitivity in the context of diagnostic accuracy, but rather describes the expected staining characteristics and reproducibility for the antibody.

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

• Normal Tissue Testing:

  • Sample Size: A "required panel of normal tissues" (number not specified) was tested, plus "three specimens of spinal cord."
  • Data Provenance: The origin of these tissues (e.g., country) is not specified. The tissues were "formalin fixed and paraffin embedded." The study is retrospective, utilizing archived tissue samples.

• Reproducibility Testing:

  • Sample Size: Eight serial sections from each of "three different paraffin embedded blocks of Hodgkin's Lymphoma" were used. Total sections: 3 blocks * 8 sections/block = 24 sections.
  • Data Provenance: Described as "pre-screened for low antigen density" Hodgkin's Lymphoma. The data provenance (e.g., country) is not specified. This is a retrospective study using archived paraffin-embedded tissue blocks.

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

The submission does not explicitly state the number of experts or their qualifications that established the "ground truth" for the test sets (normal tissues or Hodgkin's Lymphoma blocks). However, for the Hodgkin's Lymphoma blocks, they were "pre-screened for low antigen density," which implies expert pathological evaluation prior to the study. For normal tissues, the expectation is that their histological classification was already established. The overall interpretation of results would be performed by a "qualified individual having knowledge of all the potential antibody reactivities," as stated in the intended use. In the context of 1997 submissions, this typically implies a board-certified pathologist.

4. Adjudication Method for the Test Set

The adjudication method is not explicitly described. Given the descriptive nature of the results ("exhibiting positive staining," "consistent results"), it appears that a single expert or a consensus view was used to determine the staining presence and pattern for both normal tissue testing and reproducibility. There is no mention of a formal adjudication process like 2+1 or 3+1.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. The study focuses on the performance of the antibody itself (staining characteristics and reproducibility), not on the impact of AI assistance on human reader performance.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone study was performed. The device is a diagnostic antibody, and the studies describe the performance of this reagent in identifying the CD30 antigen in tissues. There is no "human-in-the-loop" component in the sense of an AI algorithm assisting a human. The human (pathologist) is the ultimate interpreter of the staining results. The studies assess the standalone performance of the antibody reagent.

7. Type of Ground Truth Used

• Normal Tissue Testing: The ground truth for normal tissues was based on established histological classification (e.g., bone marrow, brain, spinal cord, tonsil were identified as such) and known, expected CD30 expression patterns from existing literature and previous experience with the antigen.
• Reproducibility Testing: The ground truth for Hodgkin's Lymphoma cases was based on their documented diagnosis as Hodgkin's Lymphoma (and "pre-screened for low antigen density"). The expectation was that these tissues should show CD30 positivity, and the study aimed to demonstrate consistent detection of this positivity.

8. Sample Size for the Training Set

This product is an antibody, not a machine learning algorithm. Therefore, there is no "training set" in the computational sense. The antibody's characteristics (clone Ber-H2) and known reactivity profile would have been established through extensive research and development prior to these validation studies.

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

As there is no "training set" in the context of an AI algorithm, this question is not applicable. The development of the Ber-H2 clone would have involved immunogen presentation, antibody production, screening against known positive and negative cell lines/tissues, and characterization through various immunological assays, all guided by established scientific methods and expert biological knowledge of CD30 antigen expression.

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Monoclonal Mouse Anti-Human Leukocyte Common Antigen, CD45, FITC-Conjugated, Clone T29/33 Monocrollar Wouse First House Anti-Human Mouse Anti-Human Monocyte. CD14, RPE-Conjugated, Clone TUK4 (Anti-CD) 1/RPE, TÜK4) have been developed for use in flow cytometry. This reagent may be used to optimize the gating of lymphocytes when analyzing peripheral whole blood or peripheral blood mononuclear cell preparations. This reagent is one component of the suggested monoclonal antibody (MAb) combination for routine immunophenoryping of lymphocytes in peripheral blood.

Purified mouse anti-human CD45, Clone T29/33, conjugated with fluorescein isothiocyanate, isomer 1 (FITC) + purified mouse anti-human CD14, Clone TUK4, conjugated with R-phycoerythrin, present in 0.05M Tris-HCl buffer, pH 7.2, 15 mM NaN3, 0.1M NaCl, stabilized with 1% carrier protein

Subpopulations of lymphocytes may be stained with fluorochrome-conjugated antibody and evaluated in peripheral blood specimens when contaminating red blood cells (RBC's) are lysed prior to flow cytometric analysis. A subpopulation of WBC's are selected for assessment based upon cell morphology.

Here's an analysis of the provided text, outlining the acceptance criteria and study details as requested:

Acceptance Criteria and Device Performance

Study Details

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

   • Linearity (Anti-CD45/FITC): Not explicitly stated how many individual cells/samples were used, but it involved serial dilutions of Raji (antigenic) and U937 (non-antigenic) cell lines.
   • Reproducibility: 10 replicates from peripheral blood of one donor per test (for each of two flow cytometers and each antibody). Data provenance is DAKO Corporation internal testing.
   • Specificity: 5 apparently healthy adult donors (3 Caucasians, 1 Asian, 1 Hispanic) for basic specificity. Data provenance is DAKO Corporation internal testing.
   • Correlation to Predicate Device: 150 normal, apparently healthy individuals and 27 samples from ill patients. These were tested at three geographically separate laboratories. Data provenance is multi-site, multi-ethnic (implied by "normal, apparently healthy individuals"), and appears to be prospective for the purpose of this comparison.

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

   • The document does not mention experts being used to establish ground truth for the specific performance evaluation (reproducibility, specificity, linearity). These appear to be laboratory measurements against known cell lines or direct observation of antibody binding.
   • For the correlation study against the predicate device, the "ground truth" is essentially the results obtained from the predicate device itself. The document does not specify if experts verified these predicate results.
   • The "Leukocyte Typing Workshops" (Third, Fourth, Fifth) are cited as providing information that contributes to the conclusions, implying a broader expert consensus within the scientific community for the validity of the clones used (T29/33 and TUK4). However, these workshops did not establish the ground truth for this specific device's test set.

3. Adjudication method for the test set:

   • No adjudication method is described for the direct performance studies (linearity, reproducibility, specificity).
   • For the correlation study, duplicate samples were tested with each reagent, suggesting comparative measurement rather than adjudication by experts.

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 MRMC comparative effectiveness study was done. This device is an in vitro diagnostic reagent and accessory for flow cytometry, not an AI or imaging device where "human readers" typically interpret results with or without assistance in the conventional sense. The "reading" is done by the flow cytometer, and the results are numerical.

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

   • This is not applicable as the device is a reagent for flow cytometry, not an algorithm. The flow cytometer itself performs the "standalone" measurement, and human operators perform sample preparation, instrument setup, and interpretation of the numerical results produced by the instrument. The "algorithm" here would be the flow cytometer's software, which is part of the system the reagent is designed to be used with.

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

   • Linearity: Based on known antigenic expression of established cell lines (Raji and U937).
   • Reproducibility: Based on direct measurements from a single donor's peripheral blood run multiple times.
   • Specificity: Based on observed antibody binding to different cell populations (RBCs, granulocytes, monocytes, lymphocytes, platelets) in apparently healthy donors, with cell identification likely based on morphology and characteristic light scatter patterns in flow cytometry, consistent with cellular biology.
   • Correlation to Predicate Device: The "ground truth" for the comparative study was the results obtained from the predicate device (Becton Dickinson Simultest LeucoGATE) on the same samples. These predicate results are assumed to be a valid measurement.

7. The sample size for the training set:

   • This is not applicable. The device is a diagnostic reagent, not a machine learning algorithm that requires a "training set." The development of the monoclonal antibodies (clones T29/33 and TUK4) themselves would have involved extensive R&D, but that is not an "algorithm training set" in the modern sense.

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

   • Not applicable, as there is no "training set" for this type of device.

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For In Vitro Diagnostic Use Mouse Anti-Human T-cell, CD3/FITC, UCHT1 + - Mouse Anti-Human T-cell, CD4/RPE, MT310 (DAKO Anti-CD3/FITC and Anti-CD4/RPE) has been developed for use in flow cytometry for the analysis of CD3 and CD4* T-cells. This reagent allows simultaneous detection and quantification of CD3CD4 cells (CD4 positive T-lymphocytes) in normal and pathological conditions such as immunodeficiency disorders. It is one component of the suggested monoclonal antibody (MAb) combinations for routine immunophenotyping of lymphocytes in peripheral blood using flow cytometry.

Purified mouse anti-human CD3, Clone UCHT1, conjugated with fluorescein isothiocyanate, isomer 1 (FITC) + purified mouse anti-human CD4, Clone MT310, conjugated with R-phycoerythrin, present in 0.05M Tris-HCl buffer, pH 7.2, 15 mM NaNo, 0.1M NaCl, stabilized with 1% carrier protein Subpopulations of lymphocytes may be stained with fluorochrome-conjugated antibody and evaluated in peripheral blood specimens when contaminating red blood cells (RBC's) are lysed prior to flow cytometric analysis. A subpopulation of WBC's are selected for assessment based upon cell morphology.

Here's an analysis of the provided text, focusing on the acceptance criteria and the study details:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document states that the correlation "approached a direct 1:1 comparison," which is a qualitative description supporting the quantitative correlation of >0.96. The document doesn't explicitly list "acceptance criteria" but rather presents "technological performance characteristics" that were evaluated. The table above frames these evaluations as implicit acceptance criteria based on the demonstrated performance.

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

• Sample Size: The document mentions "peripheral blood samples obtained from apparently healthy adults." It does not specify an exact number of samples or subjects.
• Data Provenance: The data appears to be prospective as it describes the completion of "flow cytometric tests of peripheral blood samples." The country of origin is not explicitly stated.

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

• The concept of "experts" establishing ground truth in the traditional sense (e.g., radiologists interpreting images) is not directly applicable here.
• The ground truth in this context is established by the predicate devices (DAKO CD3/FITC and DAKO CD4/RPE), which are previously FDA-cleared monoclconal antibodies for measuring CD3 and CD4+ T-cells using flow cytometry.
• The initial validation of the antibody clones (UCHT1 for CD3 and MT310 for CD4) was done at international workshops: the First Leukocyte Typing Workshop (Paris, 1982) and the Second Leukocyte Typing Workshop (Boston, 1984), respectively. These workshops involved numerous scientific experts in immunology and cell typing, whose collective findings established the specificity and identity of these markers.

4. Adjudication Method for the Test Set

• No explicit adjudication method (like 2+1 or 3+1) is mentioned, nor is it typically relevant for this type of in vitro diagnostic device. The comparison is against established predicate devices, which serve as the reference.

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

• No, an MRMC comparative effectiveness study was not done. This type of study typically involves multiple human readers evaluating cases with and without AI assistance to measure improvements in diagnostic performance. The device described is a flow cytometry reagent, not an AI-powered diagnostic imaging tool.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• Yes, the study is essentially "standalone" in principle, but the concept of "algorithm" is different. The device itself (the reagent) is evaluated for its direct performance in detecting and enumerating cell populations using flow cytometry. While a human operates the flow cytometer and interprets the data, the performance being tested is that of the reagent itself in yielding accurate counts when compared to a reference standard (predicate devices). There is no "AI algorithm" involved in the sense of a software interpreting images or other complex data autonomously.

7. Type of Ground Truth Used

• The ground truth is established by the performance of predicate devices (DAKO CD3/FITC and DAKO CD4/RPE), which are themselves previously cleared and validated reagents for the accurate measurement of CD3 and CD4+ T-cells.
• Further foundational ground truth for the antibody clones was established through expert consensus (clustering at leukocyte typing workshops) regarding their specificity for the target antigens.

8. Sample Size for the Training Set

• The document does not report a separate "training set" in the context of an algorithm or machine learning model. This is an immunoassay reagent, not an AI device. The development of the reagent involves laboratory work, but not "training data" in the AI sense.

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

• Since there's no "training set" for an algorithm in this context, this question is not applicable. The development of the individual antibody clones (UCHT1 and MT310) involved extensive biological research and validation, including the clustering at leukocyte typing workshops, to establish their specificity and utility.

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Immunoenzymatic/immunohistochemical (IHC) staining techniques allow for the qualitative identification of tissue antigens. Antigens are visualized via the sequential application of a specific antibody to the antigen (primary antibody) and a detection system. Immunohistochemical detection systems usually consist of a secondary antibody to the primary antibody (link antibody), an enzyme complex and a chromogenic substrate. The enzymatic activation of the chromogen yields a visible reaction product at the antigen site. Results aid in the diagnosis of pathophysiological processes which may or may not be associated with a particular antigen.

The DAKO LSAB® 2 Kit, HRP (Code No. K0677) is based on a modified labeled avidin-biotin (LAB) technique in which a biotinylated secondary antibody forms a complex with peroxidase-conjugated streptavidin molecules. This kit is very similar to the original DAKO LSAB® Kit, HRP (K0680) previously cleared in submission K924726. Refinements to the LSAB® 2 Kit include the elimination of a separate protein blocking reagent incubation and reconfigured substrate-chromogen reagents.

The DAKO Envision™ Systems, HRP, contains a Peroxidase Blocking Reagent similar to the Hydrogen Peroxide provided with the LSAB® and LSAB® 2 Kit, the Envision™ System does not require a protein blocking reagent incubation. The Envision™ System also eliminates the sequential applications of link antibody and streptavidin common to the LSAB® 2 Kits. A polymer, labeled with goat anti-mouse and goat anti-rabbit immunoglobulins conjugated to horseradish peroxidase eliminates these steps. The DAKO Envision™ System offers the user a choice of two protocols. Protocol #1 consecutively incubates the primary antibody and Peroxidase Labeled Polymer for ten (10) minutes. Protocol #2 increases the staining intensity of the Envision™ System by lengthening the incubations of the primary antibody and the labeled polymer to thirty (30) minutes. The DAKO Envision™ System. HRP, is available with DAB (Code No. K1390) or Ready-to-Use AEC substrate-chromogen (Code No. K1391). Both systems use the same Peroxidase Blocking Reagent and Peroxidase Labeled Polymer.

Concentrated primary rabbit/mouse antibodies or DAKO® Ready-to-Use N-Series Primary Antibodies and Negative Control Reagents are suitable for use with the DAKO LSAB® 2 Kit and DAKQ Envision™ Systems. Primary antibodies are not included with the DAKO LSAB® 2 Kit, HRP or DAKO Envision™ Systems, and must be purchased separately by the user.

The provided text describes the DAKO LSAB® 2 Kit, HRP, and DAKO Envision™ Systems, HRP, which are immunohistochemical (IHC) staining systems used for qualitative identification of tissue antigens. The document is a Summary of Safety and Effectiveness for a K951965 submission.

Here's an analysis of the provided information against the requested categories:

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

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

• Sample Size: The document repeatedly mentions "all test specimens" and specific tissue types like "tonsil" and "melanoma", and "liver," "kidney," and "lymphoid tissues." However, no specific numerical sample sizes are provided for any of the comparative tests. The sample size for the comparison of LSAB2 with 2-component AEC versus ready-to-use AEC for specific antibodies (LCA, UCHL1, HMB45) is denoted by "N1514," "N1520," and "N1545" in parentheses next to the antibody names, implying these might refer to specific tissue samples or an internal numbering system, but the actual number of specimens is not listed.
• Data Provenance: The document does not specify the country of origin of the data. The data appears to be retrospective in nature, as it describes comparisons of the new devices against existing products using various tissue types.

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 specify the number of experts used to establish the ground truth or interpret the results.
• It also does not provide any qualifications for the individuals who performed the interpretation/evaluation ("Equivalent interpretive results were observed," "Results showed that the same level of staining was obtained," "Background staining... evaluated as negative").

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

• The document does not describe any formal adjudication method for the test set. The evaluations appear to be direct comparisons of staining results.

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 MRMC comparative effectiveness study was performed.
• This device is an IHC staining kit, not an AI or imaging diagnostic device. Therefore, the concept of "human readers improve with AI vs. without AI assistance" is not applicable here.

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

• This question is not applicable as the device is an IHC staining kit and not an algorithm or AI system.

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

• The ground truth appears to be based on visual interpretation of staining results by unspecified individuals, likely experienced researchers or pathologists within DAKO, evaluating "equivalent interpretive results," "level of staining," and "background staining." This is implicitly based on established immunohistochemical principles and the expected reactivity of the primary antibodies on the tested tissues.

8. The sample size for the training set

• The document describes comparative testing of new kits against existing kits and variations within the new kits. It does not mention a "training set" in the context of machine learning or algorithm development, as these are chemical kits. All described tests appear to be evaluations of the final products.

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

• As there is no "training set" in the context of this device type, this question is not applicable. The "ground truth" for the performance evaluations (test sets) was established by visual assessment of staining consistency and intensity by presumably qualified personnel.

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