(322 days)
This antibody is intended for in vitro diagnostic (IVD) use. CONFIRM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal (IgG) Primary Antibody is intended for laboratory use for the qualitative detection of progesterone receptor (PR) antigen in sections of formalin-fixed, paraffin-embedded tissue on a VENTANA automated slide stainer with VENTANA detection kits and ancillary reagents. CONFIRM anti-PR (1E2) is directed against an epitope present on human progesterone receptor protein located in the nucleus of PR positive normal and neoplastic cells. CONFIRM anti-PR (1E2) is indicated as an aid in the management, prognosis, and prediction of hormone therapy for breast carcinoma. This product should be interpreted by a qualified pathologist in conjunction with histological examination, relevant clinical information, and proper controls. Prescription use only.
Ventana's CONFIRM anti-Progesterone Receptor (1E2) Rabbit Monoclonal Primary Antibody specifically binds to progesterone receptor antigen located in the nuclear region of a variety of normal and neoplastic tissues. The antibody is diluted in 0.05 M Tris-HCl with 2% carrier protein, and 0.1% ProClin 300, a preservative. There is trace (0.2%) fetal calf serum of U.S. origin from the stock solution. Total protein concentration of the reagent is approximately 10 mg/mL. Specific antibody concentration is approximately 1 µg/mL. CONFIRM anti-PR (1E2) is a rabbit monoclonal antibody produced as a cell culture supernatant.
The provided text describes the 510(k) summary for the CONFIRM anti-Progesterone Receptor (1E2) Rabbit Monoclonal Primary Antibody. This document focuses on demonstrating substantial equivalence to a predicate device, rather than defining and proving against specific acceptance criteria for a novel device. Therefore, the information typically requested for acceptance criteria and a study proving a device meets those criteria is not explicitly presented in the same way as for a de novo device or a device with new performance claims.
Instead, the study aims to show agreement between the new device and the predicate device. The acceptance criteria, therefore, are implicitly related to achieving a high level of agreement.
Here's an interpretation based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
Implicit Acceptance Criteria for Substantial Equivalence:
| Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Agreement with Predicate) |
|---|---|---|
| Positive Agreement | High level of agreement with the predicate device (implied > 85%) | CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%.CONFIRM anti-PR (1E2) on BenchMark XT vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%.CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. CONFIRM anti-PR (1E2) on BenchMark XT: Greater than 85%. |
| Negative Agreement | High level of agreement with the predicate device (implied > 85%) | CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%.CONFIRM anti-PR (1E2) on BenchMark XT vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%.CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. CONFIRM anti-PR (1E2) on BenchMark XT: Greater than 85%. |
| Overall Agreement | High level of agreement with the predicate device (implied > 85%) and between different platforms of the new device (implied > 85%) | CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%.CONFIRM anti-PR (1E2) on BenchMark XT vs. FLEX anti-PgR (636) on Dako Autostainer Plus: Greater than 85%.CONFIRM anti-PR (1E2) on BenchMark ULTRA vs. CONFIRM anti-PR (1E2) on BenchMark XT: Greater than 85%. |
Note: The document states "greater than 85%" for agreement rates, implying this was the threshold for acceptable performance for substantial equivalence to the predicate.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: Approximately 120 negative and 216 positive cases of breast cancer (total = 336 cases).
- Data Provenance: Not explicitly stated, but the study design suggests retrospective use of archived breast cancer tissue samples, representing a "clinical range of the assay." The cases were "randomly assigned to three study sites," which implies that the data was collected at multiple institutions. Country of origin is not mentioned.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts used to establish the ground truth for the test set. It mentions that "This product should be interpreted by a qualified pathologist in conjunction with histological examination, relevant clinical information, and proper controls." However, for the study to compare performance, it's not detailed how the initial classification of positive/negative cases was done or if an independent panel established a reference standard for the test set. Given it's a comparison study to a predicate, it's possible that the "ground truth" was established by the predicate device's results as an established standard, or by routine pathology reports prior to the study.
4. Adjudication Method for the Test Set
The adjudication method for establishing the ground truth of the test set is not explicitly mentioned. The study design focuses on comparing the staining performance of the new device against the predicate device. It does not detail a process for resolving discrepancies in initial diagnosis or a separate ground truth establishment.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, and Effect Size
Yes, a multi-site, multi-reader study was conducted.
- Type of Study: "A randomized, multi-site, multi-reader study was conducted to compare the staining performance of the CONFIRM anti-PR (1E2) on the BenchMark ULTRA instrument and on the BenchMark XT instrument to that of the Dako FLEX Monoclonal Mouse Anti-Human Progesterone Receptor Clone PgR 636 Ready-To-Use (FLEX anti-PgR (636)) on the Dako Autostainer Plus."
- Effect Size of Human Readers with vs. without AI Assistance: This information is not applicable here. This study is for an immunohistochemistry (IHC) antibody, which is a diagnostic reagent, not an AI or software device that assists human readers. The readers (pathologists) interpret the stained slides, but there is no "AI assistance" component described in this context. The study compares the performance of different reagents/platforms as interpreted by human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
This information is not applicable. The device is an antibody (reagent) for immunohistochemistry, which requires a human pathologist for interpretation. There is no algorithm or standalone performance without human interpretation.
7. The Type of Ground Truth Used
The type of ground truth used is not explicitly stated as a separate, independently established reference standard. Given the nature of a substantial equivalence study for an IHC antibody, the "ground truth" for comparison is likely the performance or results obtained using the predicate device (Dako FLEX Monoclonal Mouse Anti-Human Progesterone Receptor Clone PgR 636) or potentially prevailing clinical consensus based on established pathological diagnosis of the breast cancer cases included in the study. The study measures agreement with the predicate.
8. The Sample Size for the Training Set
No training set is mentioned or applicable for this type of device. The CONFIRM anti-PR (1E2) is a monoclonal antibody (a biological reagent), not a machine learning model that requires training data. Non-clinical performance data included testing on a "required panel of normal tissues" for tissue specificity, but this is not a "training set" in the context of an AI/ML device.
9. 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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NOV 1 6 2011
510(k) Summary
Submitted By:
Submitter: Ventana Medical Systems, Inc. George De La Rosa Contact: Date Prepared: November 15, 2011
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.
The assigned 510(k) number is: K103818
| Device Name | CONFIRM anti-Progesterone Receptor (1E2) Rabbit Monoclonal Primary Antibody |
|---|---|
| Antibody for aid in the detection of progesterone receptor (PGR)Common name:antigen in histological tissue sections | |
| Classification:Class II Non-exempt | |
| Product Code:MXZ | |
| PredicateDevice | CONFIRM anti-Progesterone Receptor (1E2) Rabbit Monoclonal Primary Antibody issubstantially equivalent to DAKO North America's commercially available MonoclonalMouse Anti Human Progesterone Receptor, Clone PGR 636 |
| K020023 | |
| DeviceDescription | Ventana's CONFIRM anti-Progesterone Receptor (1E2) Rabbit Monoclonal PrimaryAntibody specifically binds to progesterone receptor antigen located in the nuclearregion of a variety of normal and neoplastic tissues. The antibody is diluted in 0.05 MTris-HCl with 2% carrier protein, and 0.1% ProClin 300, a preservative. There is trace(0.2%) fetal calf serum of U.S. origin from the stock solution. Total proteinconcentration of the reagent is approximately 10 mg/mL. Specific antibodyconcentration is approximately 1 µg/mL. CONFIRM anti-PR (1E2) is a rabbitmonoclonal antibody produced as a cell culture supernatant. |
| Intended Use | This antibody is intended for in vitro diagnostic (IVD) use. |
| CONFIRM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal (IgG)Primary Antibody is intended for laboratory use for the qualitative detection ofprogesterone receptor (PR) antigen in sections of formalin-fixed, paraffin-embedded tissue on a VENTANA automated slide stainer with VENTANAdetection kits and ancillary reagents. CONFIRM anti-PR (1E2) is directedagainst an epitope present on human progesterone receptor protein located inthe nucleus of PR positive normal and neoplastic cells. CONFIRM anti-PR(1E2) is indicated as an aid in the management, prognosis, and prediction ofhormone therapy for breast carcinoma. | |
| This product should be interpreted by a qualified pathologist in conjunctionwith histological examination, relevant clinical information, and proper controls. | |
| Prescription use only. | |
| Summary ofthe new andpredicatedevices | CONFIRM anti-PR (1E2) is a rabbit monoclonal antibody that recognizes the A and Bforms of human progesterone receptor. The immunogen was developed from asynthetic peptide identified as an area of potential high antigenicity common toprogesterone receptor A and B forms. The peptide was synthesized and covalentlybound to keyhole limpet hemocyanin to further increase antigenicity. CONFIRM anti-PR (1E2) has been shown to react with 60 kD, 87 kD and 110 kD proteins from T47D |
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| cells via Western blotting. The protein sizes are in agreement with the predictedmolecular weight of progesterone receptor forms A, B and C.1.2 | |
|---|---|
| Dako FLEX Monoclonal Mouse Anti-Human Progesterone Receptor Clone PgR 636consists of a mouse anti-human monoclonal antibody produced as a tissue culturesupernatant is used in the qualitative detection of human progesterone receptor intissue sections of human breast cancer by immunohistochemistry. | |
| Both products specifically bind to progesterone receptor proteins located in the nucleiof cells, and these products require similar detection chemistry principles forvisualization of the product, and both aid in the prognosis of breast carcinoma. | |
| Non-clinicalperformancedata | Distribution of progesterone receptor throughout normal tissue has been reported in avariety of studies. The required panel of normal tissues was tested with this antibodyas specified in the 6/3/98 final version of Guidance for Submissions ofImmunohistochemistry Applications to the FDA. All tissues were formalin fixed andparaffin embedded. |
| Non-clinical performance testing has been conducted to demonstrate performancecharacteristics of CONFIRM anti-PR (1E2). Results of tissue-specificity and precisiontesting are noted in the product package insert. | |
| Clinicalperformancedata | A randomized, multi-site, multi-reader study was conducted to compare the stainingperformance of the CONFIRM anti-PR (1E2) on the BenchMark ULTRA instrumentand on the BenchMark XT instrument to that of the Dako FLEX Monoclonal MouseAnti-Human Progesterone Receptor Clone PgR 636 Ready-To-Use (FLEX anti-PgR(636)) on the Dako Autostainer Plus. |
| Approximately 120 negative and 216 positive cases of breast cancer, representing theclinical range of the assay, were randomly assigned to three study sites such thateach site received an equal number of cases and each site received casesrepresenting each clinical assessment category. | |
| For CONFIRM anti-PR (1E2) staining on the BenchMark ULTRA instrument comparedto the FLEX anti-PgR (636) on the Dako Autostainer Plus, the positive, negative, andoverall agreement rates (pooled across all testing sites) were greater than 85%. ForCONFIRM anti-PR (1E2) staining on the BenchMark XT instrument compared to the | |
| FLEX anti-PgR (636) on the Dako Autostainer Plus, the positive, negative, and overallagreement rates were all greater than 85%. For CONFIRM anti-PR (1E2) staining onthe BenchMark ULTRA instrument compared to the CONFIRM anti-PR (1E2) stainingon the BenchMark XT instrument, the positive, negative, and overall agreement rates |
1 Bevitt DJ, Milton ID, Piggot N, Henry L, Carter MJ, Toms GL, Lennard TW, Westley B, Angus B, Horne CH. New Monoclonal antibodies to oestrogen and progesterone receptors effective for paraffin section immunohistorhemistry. J Pathol. 1997;183(2):228-232.
² Dickson RB, Lippman ME. Genes, oncogenes, and hormones: advances in cellular and
molecular biology of breast cancer. Kluwer Academic Publishers, Boston, 1992: 285-286
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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Ventana Medical Systems, Inc. c/o Mr. George De La Rosa Manager, Regulatory Affairs 1910 E. Innovation Park Drive Tucson, AZ 85755
NOV 1 6 2011
Re: K103818
Trade/Device Name: CONFIRM anti-Progesterone Receptor (1E2) Rabbit Monoclonal Primary Antibody Regulation Number: 21 CFR § 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Codes: MXZ Dated: October 26, 2011 Received: October 27, 2011
Dear Mr. De La Rosa:
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.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of
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Page 2 – Mr. George De La Rosa
substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market. If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely vours.
mchan
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number: K103818
Device Name: CONFIRM Anti-Progesterone Receptor (1E2) Rabbit Monoclonal Primary Antibody
This antibody is intended for in vitro diagnostic (IVD) use.
CONFIRM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal (IgG) Primary Antibody is intended for laboratory use for the qualitative detection of progesterone receptor (PR) antigen in sections of formalin-fixed, paraffin-embedded tissue on a VENTANA automated slide stainer with VENTANA detection kits and ancillary reagents. CONFIRM anti-PR (1E2) is directed against an epitope present on human progesterone receptor protein located in the nucleus of PR positive normal and neoplastic cells. CONFIRM anti-PR (1E2) is indicated as an aid in the management, prognosis, and prediction of hormone therapy for breast carcinoma.
This product should be interpreted by a qualified pathologist in conjunction with histological examination, relevant clinical information, and proper controls.
Prescription use only.
Prescription Use × (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Seuk R. S
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K103818
Page 1 of
§ 864.1860 Immunohistochemistry reagents and kits.
(a)
Identification. Immunohistochemistry test systems (IHC's) are in vitro diagnostic devices consisting of polyclonal or monoclonal antibodies labeled with directions for use and performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for use with flow cytometry devices are not considered IHC's.(b)
Classification of immunohistochemistry devices. (1) Class I (general controls). Except as described in paragraphs (b)(2) and (b)(3) of this section, these devices are exempt from the premarket notification requirements in part 807, subpart E of this chapter. This exemption applies to IHC's that provide the pathologist with adjunctive diagnostic information that may be incorporated into the pathologist's report, but that is not ordinarily reported to the clinician as an independent finding. These IHC's are used after the primary diagnosis of tumor (neoplasm) has been made by conventional histopathology using nonimmunologic histochemical stains, such as hematoxylin and eosin. Examples of class I IHC's are differentiation markers that are used as adjunctive tests to subclassify tumors, such as keratin.(2) Class II (special control, guidance document: “FDA Guidance for Submission of Immunohistochemistry Applications to the FDA,” Center for Devices and Radiologic Health, 1998). These IHC's are intended for the detection and/or measurement of certain target analytes in order to provide prognostic or predictive data that are not directly confirmed by routine histopathologic internal and external control specimens. These IHC's provide the pathologist with information that is ordinarily reported as independent diagnostic information to the ordering clinician, and the claims associated with these data are widely accepted and supported by valid scientific evidence. Examples of class II IHC's are those intended for semiquantitative measurement of an analyte, such as hormone receptors in breast cancer.
(3) Class III (premarket approval). IHC's intended for any use not described in paragraphs (b)(1) or (b)(2) of this section.
(c)
Date of PMA or notice of completion of a PDP is required. As of May 28, 1976, an approval under section 515 of the Federal Food, Drug, and Cosmetic Act is required for any device described in paragraph (b)(3) of this section before this device may be commercially distributed. See § 864.3.