The VENTANA CD30 (Ber-H2) Assay is intended for laboratory use in the qualitative detection of the CD30 protein in formalin-fixed, paraffin-embedded tissue stained with a VENTANA BenchMark ULTRA instrument and OptiView DAB IHC Detection Kit. CD30 positive staining may aid in the identification of classical Hodgkin lymphoma (cHL), anaplastic large cell lymphoma (ALCL) and cutaneous T-cell lymphoma (CTCL). This product should be interpreted by a qualified pathologist in conjunction with histological examination, relevant clinical information and proper controls. This antibody is intended for in vitro diagnostic (IVD) use.

Device Description

The VENTANA CD30 (Ber-H2) Assay consists of the primary CD30 (Ber-H2) antibody, detection reagents and an instrument (BenchMark ULTRA automated staining instrument). The VENTANA CD30 (Ber-H2) Assay is a mouse monoclonal antibody (IgG1, kappa) directed against CD30. CD30 antigen is expressed in mononuclear Hodgkin's cells and multinucleated Reed Sternberg cells of Hodgkin Lymphoma as well as on anaplastic large cell lymphomas. This antibody variably produces membranous, cytoplasmic, and Golgi staining of both lymphoma cells and of scattered large activated B and T cells in lymph nodes, spleen, tonsil, and thymus. The OptiView DAB IHC Detection Kit is an indirect, biotin-free system for detecting mouse IgG, mouse IgM, and rabbit primary antibodies. This kit is intended to detect antigens by IHC in sections of formalin-fixed, paraffin-embedded (FFPE) and frozen tissues that are stained on the BenchMark ULTRA instrument (note: the VENTANA CD30 (Ber-H2) Assay will not be recommended for use in frozen tissue). The OptiView DAB IHC Detection Kit produces a visible dark brown precipitate (3, 3'-Diaminobenzidine) via a horseradish peroxidase (HRP) enzymatic reaction at the antigen site. The Pathologist evaluates the brown precipitate using Bright-field microscopy.

AI/ML Overview

The provided text describes the 510(k) summary for the VENTANA CD30 (Ber-H2) Assay, an immunohistochemistry (IHC) assay. It details the device's intended use and compares it to a predicate device to demonstrate substantial equivalence.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

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

The document implicitly defines acceptance criteria through the comparison to the predicate device. The primary stated performance metric is "overall percent agreement rate".

Acceptance Criteria / Performance Metric	Reported Device Performance (VENTANA CD30 (Ber-H2) Assay)
High overall percent agreement rate with predicate device (DAKO K965022).	91.0% (517/568) overall agreement rate between three readers92.8% (739/796) overall agreement rate between four readers
Substantial equivalence to predicate device (DAKO K965022) in relevant characteristics and performance.	Concluded that the VENTANA CD30 (Ber-H2) Assay and the predicate DAKO K965022 device are substantially equivalent.

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

Test Set Sample Size: The text mentions two sample sizes based on the number of readers:
- 568 cases for the study involving three readers (resulting in 517 agreed cases).
- 796 cases for the study involving four readers (resulting in 739 agreed cases).
Data Provenance: The document does not explicitly state the country of origin. It indicates the study was a "premethod comparison study" conducted to demonstrate substantial equivalence. It's implied to be retrospective, as it compares the new device's staining results to those obtained with cases using the predicate device. The samples are described as "formalin-fixed, paraffin-embedded human tissue."

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

Number of Experts: The study used three readers for one analysis and four readers for another.
Qualifications of Experts: The document states that the product "should be interpreted by a qualified pathologist." While it doesn't provide specific experience levels (e.g., "10 years of experience"), it implies that the readers involved in the comparison study were qualified pathologists.

4. Adjudication method for the test set:

The document mentions "overall percent agreement rate between three readers" and "overall agreement rate between four readers." This strongly suggests a consensus-based adjudication method, where the aggregate agreement among the multiple readers determines the final result used for comparison. It doesn't specify if a particular threshold for agreement was used (e.g., 2 out of 3, or majority rule), but the "agreement rate" implies a comparison of individual reader interpretations against each other or potentially against a predefined "truth" established by the collective. It's not a 2+1 or 3+1 method explicitly stated, but rather a direct comparison of agreement.

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:

MRMC Study: Yes, a multi-reader multi-case comparison study was implicitly done, as the performance metrics are based on agreement rates between multiple readers on a set of cases using both the new and predicate devices.
Effect Size (AI Assistance): This study is not an AI-assisted study. It compares a new IHC assay (VENTANA CD30 (Ber-H2) Assay) against a predicate IHC assay (DAKO K965022). Therefore, there is no AI component and no mention of human readers improving with AI assistance.

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

This is an IHC assay, not an AI algorithm. The performance is inherently tied to the visual interpretation of stained tissue by a pathologist. Therefore, a standalone (algorithm only) performance is not applicable or discussed. The device is a reagent and an automated staining instrument for pathologist interpretation.

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

The ground truth for this study appears to be expert consensus among the pathologists interpreting the slides stained with both the predicate and proposed devices. The "overall percent agreement rate" signifies how well the new device's results align with the interpretations obtained from the predicate device, or how consistently different pathologists interpreted the slides stained by the new device. The predicate device's performance, previously cleared by the FDA, serves as the reference for substantial equivalence.

8. The sample size for the training set:

The document does not explicitly mention a training set sample size. This is an analytical validation and method comparison study for a diagnostic assay, not a machine learning model. Therefore, the concept of a "training set" in the context of AI is not relevant here. The samples used are for the comparison study itself.

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

As this is not an AI/machine learning study, the concept of a "training set" and establishing its ground truth in that context is not applicable. The study focuses on demonstrating substantial equivalence of the new IHC assay to an existing, cleared predicate device through a comparison study. The "ground truth" in this context is the established performance and interpretation patterns of the predicate device, against which the new device's performance is measured by experienced pathologists.

Summary

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May 8, 2018

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Ventana Medical Systems, Inc. Jeffrey M. Catania, Ph.D. Regulatory Affairs Director 1910 E. Innovation Park Dr. Tucson, Arizona 87555

Re: K172471

Trade/Device Name: VENTANA CD30 (Ber-H2) Assay Regulation Number: 21 CFR 866.5550 Regulation Name: Immunoglobulin (light chain specific) immunological test system Regulatory Class: Class II Product Code: DEH Dated: April 5, 2018 Received: April 6, 2018

Dear Dr. Jeffrey Catania:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

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Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Donna M. Roscoe -S 2018.05.08 15:17:03 -04'00'

For Reena Philip, Ph.D. Director Division of Molecular Genetics and Pathology Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K172471

Device Name VENTANA CD30 (Ber-H2) Assay

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

Submitter:	Ventana Medical Systems, Inc.1910 E Innovation Park DriveTucson, AZ 85755(520) 887-2155
Contact:	Jeffrey Catania
Date Prepared:	04-May-2018
510(K):	K172471

510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

This 510(k) has not yet been assigned a number.

Device Name	Proprietary Name: VENTANA CD30 (Ber-H2) Assay
	Classification: 21CFR866.5550, Immunoglobulin (light chain specific)immunological test system.
	Product Code: DEH
Predicate Device	DAKO Corporation's Monoclonal Mouse Anti-Human Ki-1antigen, CD30,Clone Ber-H2
	K965022
Device Description	The VENTANA CD30 (Ber-H2) Assay consists of the primary CD30 (Ber-H2) antibody, detection reagents and an instrument (BenchMark ULTRAautomated staining instrument).
	The VENTANA CD30 (Ber-H2) Assay is a mouse monoclonal antibody(IgG1, kappa) directed against CD30. CD30 antigen is expressed inmononuclear Hodgkin's cells and multinucleated Reed Sternberg cells ofHodgkin Lymphoma as well as on anaplastic large cell lymphomas. Thisantibody variably produces membranous, cytoplasmic, and Golgi staining ofboth lymphoma cells and of scattered large activated B and T cells in lymphnodes, spleen, tonsil, and thymus.
	The OptiView DAB IHC Detection Kit is an indirect, biotin-free system fordetecting mouse IgG, mouse IgM, and rabbit primary antibodies. This kit isintended to detect antigens by IHC in sections of formalin-fixed, paraffin-embedded (FFPE) and frozen tissues that are stained on the BenchMarkULTRA instrument (note: the VENTANA CD30 (Ber-H2) Assay will notbe recommended for use in frozen tissue). The OptiView DAB IHCDetection Kit produces a visible dark brown precipitate (3, 3'-Diaminobenzidine) via a horseradish peroxidase (HRP) enzymatic reactionat the antigen site. The Pathologist evaluates the brown precipitate usingBright-field microscopy.
IntendedUse	The VENTANA CD30 (Ber-H2) Assay is intended for laboratory use in thequalitative detection of the CD30 protein in formalin-fixed, paraffin-embedded tissue stained with a VENTANA BenchMark ULTRA instrumentand OptiView DAB IHC Detection Kit. CD30 positive staining results mayaid in the identification of classical Hodgkin lymphoma (cHL), anaplasticlarge cell lymphoma (ALCL) and cutaneous T-cell lymphoma (CTCL).This product should be interpreted by a qualified pathologist in conjunctionwith histological examination, relevant clinical information, and propercontrols.This antibody is intended for in vitro diagnostic (IVD) use.
Summary ofthe new andpredicatedevices	VENTANA CD30 (Ber-H2) Assay consists of the primary CD30 (Ber-H2)antibody (mouse monoclonal), detection reagents and an automated staininginstrument (BenchMark ULTRA). It is intended for the qualitative detectionof CD30 by immunohistochemistry in formalin fixed, paraffin embeddedhuman tissue. The CD30 antigen is expressed in mononuclear Hodgkin'scells and multinucleated Reed Sternberg cells of Hodgkin Lymphoma aswell as on anaplastic large cell lymphomas. This antibody variably producesmembranous, cytoplasmic, and Golgi staining of both lymphoma cells andmay be used to aid in the identification of classical Hodgkin lymphoma andanaplastic large cell lymphoma.The VENTANA CD30 (Ber-H2) Assay has been compared to a predicatedevice, 'Monoclonal Mouse Anti-Human Ki-1antigen, CD30, Clone Ber-H2' developed by DAKO Corporation, which reports a similar indicationand staining pattern. The predicate was granted 510(k) clearance by FDA in1992 (K965022). The intended use of the predicate, as reported in the 1992510(k), states that, "Monoclonal mouse anti-human Ki-1 antigen, CD30,Clone Ber-H2 (Ber-H2), may be used as one member of a panel ofantibodies to aid in the differential diagnosis of large anaplastic cells ofundetermined origin. This antibody stains cell membranes of most cases ofanaplastic large cell lymphomas (ALCL), often called Ki-1 lymphomas. Italso stains cell membranes and/or cytoplasm of most Hodgkin's lymphomasThe staining pattern is most often described as strong membranous andweaker cytoplasmic, specifically paranuclear dot-positivity of the Golgiregion..."The results of testing have been compared between VENTANA CD30 (Ber-H2) Assay and the DAKO K965022 device through a premethodcomparison study. The results of the study show a 91.0% (517-568) overallpercent agreement rate between three readers and a 92.8% (739/796) overallagreement rate between four readers. It has been concluded that theVENTANA CD30 (Ber-H2) Assay and the predicate DAKO K965022device are substantially equivalent.
Non-clinicalperformancedata	Non-clinical (analytical) performance testing has been conducted to demonstrate performance characteristics of VENTANA CD30 (Ber-H2) Assay. Method Comparison studies have demonstrated substantial equivalence to predicate device (Dako K965022).

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Comparison of VENTANA CD30 (Ber-H2) to Predicate Device, DAKO CD30 (Ber-H2)
Parameter	Predicate device	Proposed device
Proprietary Name	DAKO Corporation's Monoclonal Mouse Anti-Human Ki-1antigen, CD30, Clone Ber-H2 – K965022	VENTANA CD30 (Ber-H2) Assay
FDA Classification	Class II, non-Exempt	Class II, non-Exempt
Intended Use	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 cytoplasm 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 nonhematolymphoid 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.	The VENTANA CD30 (Ber-H2) Assay is intended for laboratory use in the qualitative detection of the CD30 protein in formalin-fixed, paraffin-embedded tissue stained with a VENTANA BenchMark ULTRA instrument. CD30 positive staining results may aid in the identification of classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL). This product should be interpreted by a qualified pathologist in conjunction with histological examination, relevant clinical information and proper controls. This antibody is intended for in vitro diagnostic (IVD) use.
Comparison of VENTANA CD30 (Ber-H2) to Predicate Device, DAKO CD30 (Ber-H2)
Parameter	Predicate device	Proposed device
Proprietary Name	DAKO Corporation's MonoclonalMouse Anti-Human Ki-1antigen,CD30, Clone Ber-H2 – K965022	VENTANA CD30 (Ber-H2)Assay
Sample	Acetone fixed, frozen and formalin orB5 fixed, paraffin-embedded tissues	Formalin fixed, paraffinembedded human tissue
Assay Method	IHC	IHC
Target	CD30	CD30
Assay Format	Automated	Automated
Detection System	Direct	Direct
Visualization	Interpretation by light microscopy	Interpretation by lightmicroscopy
Intended Use Population	Hodgkin's Lymphoma and AnaplasticLarge Cell Lymphoma	Hodgkin's Lymphoma andAnaplastic Large CellLymphoma
Qualitative orQuantitative	Qualitative	Qualitative
Conclusion	VENTANA CD30 (Ber-H2) Assay is substantially equivalent to Dako's510(k) cleared cd30 Ber-H2 clone in relevant characteristics andperformance: any differences will not adversely affect safety and efficacy.

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Regulation Number and Section

§ 866.5550 Immunoglobulin (light chain specific) immunological test system.

(a)
Identification. An immunoglobulin (light chain specific) immunological test system is a device that consists of the reagents used to measure by immunochemical techniques both kappa and lambda types of light chain portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an excess of light chains are produced by the antibody-forming cells. These free light chains, unassociated with gamma globulin molecules, can be found in a patient's body fluids and tissues. Measurement of the various amounts of the different types of light chains aids in the diagnosis of multiple myeloma (cancer of antibody-forming cells), lymphocytic neoplasms (cancer of lymphoid tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus.(b)
Classification. Class II (performance standards).