(719 days)
BenchMark XT, BenchMark ULTRA
No
The device is an antibody used for staining tissue samples, interpreted by a pathologist. There is no mention of automated image analysis or algorithmic interpretation, which would be necessary for AI/ML involvement.
No.
This device is an in vitro diagnostic (IVD) intended for qualitative detection of ER antigen to aid in the management, prognosis, and prediction of hormone therapy. It is not used for treating or curing a disease or condition in a patient.
Yes
The "Intended Use / Indications for Use" section explicitly states, "This antibody is intended for in vitro diagnostic (IVD) use." It also describes the device's role as an "aid in the management, prognosis, and prediction of hormone therapy for breast carcinoma," which are diagnostic purposes. The statement "Prescription use only" further supports its diagnostic classification.
No
The device is an antibody reagent intended for in vitro diagnostic use, which is a biological product, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states in the "Intended Use / Indications for Use" section: "This antibody is intended for in vitro diagnostic (IVD) use."
N/A
Intended Use / Indications for Use
This antibody is intended for in vitro diagnostic (IVD) use.
CONFIRM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody is intended for laboratory use for the qualitative detection of estrogen receptor (ER) antigen in sections of formalin-fixed, paraffin-embedded breast tissue on a Ventana automated slide stainer with Ventana detection kits and ancillary reagents. CONFIRM anti-ER (SP1) is directed against an epitope present on human ER alpha protein located in the nucleus of ER positive normal and neoplastic cells. CONFIRM anti-ER (SP1) 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.
Product codes
MYA
Device Description
CONFIRM anti-ER (SP1) binds to human estrogen receptor alpha (ER) in paraffin embedded tissue sections. The antibody is diluted in 0.05 M Tris-HCl with 2% carrier protein, and 0.10% 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 20 mg/mL. Specific antibody concentration is approximately 1 ug/mL. CONFIRM anti-ER (SP1) is a rabbit monoclonal antibody produced as a cell culture supernatant.
CONFIRM anti-ER (SP1) is optimized for use on the BenchMark XT and BenchMark ULTRA automated slides stainers using iView DAB and ultraView DAB detection chemistries.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
breast tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
qualified pathologist / laboratory
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison: A randomized, multi-site, multi-reader study was conducted to compare the staining performance of the CONFIRM anti-ER (SPI) on the BenchMark ULTRA instrument versus the BenchMark XT instrument. One hundred twenty (120) ER negative and 132 ER positive cases of breast cancer representing the clinical range of the assay were randomly assigned to three study sites. Each site stained its assigned cases with the CONFIRM anti-ER (SP1) antibody on a BenchMark ULTRA instrument and a CONFIRM anti-ER (SP1) antibody on a BenchMark XT instrument. The stained slides were evaluated by pathologists who determined the percentage of stained tumor cells. A case was considered ER positive if there was staining of the nucleus in at least ≥1% of invasive tumor cells.
Equivalence to Predicate: A randomized, single-site, multi-reader study was conducted using a clinical cohort of 820 invasive breast cancer cases comparing the staining performance of CONFIRM anti-ER (SP1) and FLEX anti-ER (SP1) to progression-free survival outcome. Additional comparison was made to the preceding technology ligand binding assay (LBA) data available from the cohort database. Cases were included in the analyses if the patient had a confirmed diagnosis of invasive breast carcinoma and received treatment with primary surgical intervention with or without post-operative local radiation therapy followed by adjuvant tamoxifen endocrine therapy (20 mg p.o./day) for 5 years. Cases were excluded from analyses if diagnostic biopsy or primary surgical tissue specimens were unavailable, if there had been a prior cancer diagnosis (except non-melanoma skin cancer), or if the patient received prior or adjuvant chemotherapy. A total of 1907 tissue microarray cores from 594 breast cancer cases with primary tumor were stained on the BenchMark ULTRA instrument. The stained slides were evaluated by three independent pathologists who determined the percentage of stained tumor cells. A case was considered ER positive if there was staining of the nucleus in at least >1% of invasive tumor cells.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Method Comparison: In the direct comparison of CONFIRM anti-ER (SP1) on the BenchMark XT versus the BenchMark ULTRA, the overall percent agreement (OPA) for ER status (positive/negative) was 90.9 (86.2-94.1).
Equivalence to Predicate: In a direct comparison of CONFIRM anti-ER (SPI) and FLEX anti-ER (SPI) assay results, the OPA for ER status (positive/negative) was 97.8% (95% CI: 96.2-98.8%). In comparison against patient outcome, the CONFIRM anti-ER (SP1) assay and FLEX anti-ER (SP1) assay yielded identical median survival times in tamoxifen treated patients (101.6 months in ER+ patients vs 47.2 months in ER- patients). For both assays the log-rank test showed the difference between ER+/ER- relative to survival is statistically significant (P 0.999). The CONFIRM anti-ER (SP1) NPA was lower than the FLEX anti-ER (SP1) NPA with respect to LBA ER status (27.6% vs 34.5%, respectively), but the difference between NPAs (-6.9%; 95% CI: -19.6-5.8%) was not statistically significantly different from zero at the 0.05 significance level (McNemar's exact test p-value = 0.500).
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
0
Image /page/0/Picture/1 description: The image shows the word "VENTANA" in a stylized font. To the left of the word is a symbol that looks like a star or asterisk made up of small arrow shapes. The text and symbol are in black and the background is white.
Image /page/0/Picture/17 description: The image shows the word "Roche" inside of a hexagon. The word is written in a bold, sans-serif font. The hexagon is outlined in black.
DEC 1 7 2012
510(k) Summary
CONFIRM anti-Estrogen Receptor (SP1) Rabbit Monoclonal Primary Antibody
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Submitter Name: | Ventana Medical Systems, Inc |
|---|---|
| Submitter Address: | 1910 E Innovation Park Dr. |
| Tucson, AZ 85755 | |
| Submitter Telephone: | 800-227-2155 |
| Submitter Fax: | 520-229-5845 |
| Submitter Contact: | Roxane Bonner |
Date Summary was Prepared: December 14, 2012
DEVICE
Trade Name: CONFIRM anti-Estrogen Receptor (SP1) Rabbit Monoclonal Primary Antibody Common Name: CONFIRM anti-ER (SP1) Classification Name: Immunohistochemistry Antibody Assay, Estrogen Receptor
PREDICATE DEVICE
FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a Clone SP1 (K081286)
DEVICE DESCRIPTION
CONFIRM anti-ER (SP1) binds to human estrogen receptor alpha (ER) in paraffin embedded tissue sections. The antibody is diluted in 0.05 M Tris-HCl with 2% carrier protein, and 0.10% 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 20 mg/mL. Specific antibody concentration is approximately 1 ug/mL. CONFIRM anti-ER (SP1) is a rabbit monoclonal antibody produced as a cell culture supernatant.
CONFIRM anti-ER (SP1) is optimized for use on the BenchMark XT and BenchMark ULTRA automated slides stainers using iView DAB and ultraView DAB detection chemistries.
1
Image /page/1/Picture/1 description: The image shows the Roche logo. The logo is a hexagon with the word "Roche" written in bold letters inside. The hexagon is outlined in black.
INTENDED USE
This antibody is intended for in vitro diagnostic (IVD) use.
CONFIRM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody is intended for laboratory use for the qualitative detection of estrogen receptor (ER) antigen in sections of formalinfixed, paraffin-embedded breast tissue on a Ventana automated slide stainer with Ventana detection kits and ancillary reagents. CONFIRM anti-ER (SP1) is directed against an epitope present on human ER alpha protein located in the nucleus of ER positive normal and neoplastic cells. CONFIRM anti-ER (SP1) 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.
TECHNOLOGICAL CHARACTERISTICS
The CONFIRM anti-ER (SP1) product and the predicate FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a Clone SP1 product utilize the same rabbit monoclonal antibody clone (SP1) which recognizes human estrogen receptor alpha. A synthetic peptide corresponding to the Cterminal portion of the ER molecule was used as the immunogen to generate the clone. The SP1 clone has been shown to react with 66 kD protein from MCF-7 cells via Western blotting. The protein size is in agreement with that predicted from the cloning of the gene for ER.
The CONFIRM anti-ER (SP1) has the same technological characteristics as the predicate device. Both products specifically bind to estrogen receptor proteins located in the nuclei of cells, and are optimized for use on formalin-fixed paraffin embedded tissues. Both products are optimized for use on automated slide stainers using similar detection chemistry principles. Both aid in the prognosis of breast carcinoma.
METHOD COMPARISON
A randomized, multi-site, multi-reader study was conducted to compare the staining performance of the CONFIRM anti-ER (SPI) on the BenchMark ULTRA instrument versus the BenchMark XT instrument. One hundred twenty (120) ER negative and 132 ER positive cases of breast cancer representing the clinical range of the assay were randomly assigned to three study sites. Each site stained its assigned cases with the CONFIRM anti-ER (SP1) antibody on a BenchMark ULTRA instrument and a CONFIRM anti-ER (SP1) antibody on a BenchMark XT instrument. The stained slides were evaluated by pathologists who determined the percentage of stained tumor cells. A case was considered ER positive if there was staining of the nucleus in at least ≥1% of invasive tumor cells.
2
In the direct comparison of CONFIRM anti-ER (SP1) on the BenchMark XT versus the BenchMark ULTRA, the overall percent agreement (OPA) for ER status (positive/negative) was 90.9 (86.2-94.1).
EQUIVALENCE TO PREDICATE
A randomized, single-site, multi-reader study was conducted using a clinical cohort of 820 invasive breast cancer cases comparing the staining performance of CONFIRM anti-ER (SP1) and FLEX anti-ER (SP1) to progression-free survival outcome. Additional comparison was made to the preceding technology ligand binding assay (LBA) data available from the cohort database. Cases were included in the analyses if the patient had a confirmed diagnosis of invasive breast carcinoma and received treatment with primary surgical intervention with or without post-operative local radiation therapy followed by adjuvant tamoxifen endocrine therapy (20 mg p.o./day) for 5 years. Cases were excluded from analyses if diagnostic biopsy or primary surgical tissue specimens were unavailable, if there had been a prior cancer diagnosis (except non-melanoma skin cancer), or if the patient received prior or adjuvant chemotherapy. A total of 1907 tissue microarray cores from 594 breast cancer cases with primary tumor were stained on the BenchMark ULTRA instrument. The stained slides were evaluated by three independent pathologists who determined the percentage of stained tumor cells. A case was considered ER positive if there was staining of the nucleus in at least >1% of invasive tumor cells.
In a direct comparison of CONFIRM anti-ER (SPI) and FLEX anti-ER (SPI) assay results, the OPA for ER status (positive/negative) was 97.8% (95% CI: 96.2-98.8%).
In comparison against patient outcome, the CONFIRM anti-ER (SP1) assay and FLEX anti-ER (SP1) assay yielded identical median survival times in tamoxifen treated patients (101.6 months in ER+ patients vs 47.2 months in ER- patients). For both assays the log-rank test showed the difference between ER+/ER- relative to survival is statistically significant (P 0.999). The CONFIRM anti-ER (SP1) NPA was lower than the FLEX anti-ER (SP1) NPA with respect to LBA ER status (27.6% vs 34.5%, respectively), but the difference between NPAs (-6.9%; 95% CI: -19.6-5.8%) was not statistically significantly different from zero at the 0.05 significance level (McNemar's exact test p-value = 0.500).
3
Image /page/3/Picture/0 description: The image shows the word "VENTANA" in all caps next to a star-like symbol. The font is simple and sans-serif. The star symbol is made up of several angled lines that converge at the center.
Image /page/3/Picture/1 description: The image shows the Roche logo. The logo consists of the word "Roche" in bold, sans-serif font, enclosed within a hexagon. The hexagon has thick, black borders.
CONCLUSIONS
The CONFIRM anti-Estrogen Receptor (SP1) Rabbit Monoclonal Primary Antibody is substantially equivalent to the predicate FLEX Monoclonal Rabbit Anti-Human Estrogen Receptor a Clone SP1 based on their intended use and technological characteristics. In performance comparison to preceding technology (ligand binding assay) and effectiveness at predicting patient outcome for hormone therapy the assays were substantially equivalent.
4
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/4/Picture/1 description: The image contains the text 'Public Health Service'. The text is in a simple, sans-serif font and is presented in a straightforward, unadorned manner. The words are arranged on a single line, with 'Public Health' appearing above 'Service'.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002
December 17, 2012
Ventana Medical Systems, Inc. c/o Ms. Roxane Bonner 1910 E. Innovations Park Drive Tucson, AZ 85755
Re: K110215
KT10213
Trade/Device Name: CONFIRM Anti-Estrogen Receptor (SP1) Rabbit Monoclonal Antibody Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Codes: MYA Dated: November 23, 2012 Received: November 26, 2012
Dear Ms. Bonner:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your Section 3 10(t) premaince is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate 101 use stated in the encrosary to togany in the Medical Device Amendments, or to connineres pro- to may 20, 1978, the encordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). and Cosmette Act (7 Nor) that do not roques of controls provisions of the Act. 1 bu may, therefore, market the do received to requirements for annual registration, listing of The general controls provisions and prohibitions against misbranding and adulteration.
If your device is classified (see above) into class II (Special Controls), it may be subject to such 11 your device is clussified (ooo acorre) and one affecting your device can be found in Title 21, additional controls: Existing mayor 19gets 800 to 895. In addition, FDA may publish further Cour of Pourer - concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean Please be advised that I Dri- 3 issualled on a ballering ther requirements of the Act
that FDA has made a determination that your device complies with other requirements of t that FDA has made a determination administered by other Federal agencies. You must of any I cucharies and regulations and limited to: registration and listing (21 Comply with an the Free oreans 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice medical device-related develop volity systems (QS) regulation (21 CFR Part 820). This letter requirements as set form in the quality of the as described in your Section 510(k) premarket will anow you to begin marketing your ence of your device to a legally marketed
5
Page 2 - Ms. Roxane Bonner
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 If you desire specific advice for your der your Diagnostics and Radiological Health at (301) 796-007), prease contact 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
under the MDN regulation (27 Of N Part 8,07) Posts of Santalian 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 Tou may other general 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 yours,
Maria M. Chan
Maria M. Chan, Ph.D.
Director Division of Immunology and Hematology Devices
Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
6
Indications for Use
510(k) Number: K110215
Device Name:
CONFIRM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody
Indications for Use:
This antibody is intended for in vitro diagnostic (IVD) use.
CONFIRM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody is intended for CONY Inn antir-Latrogen Friceptor (EP) (ST 1) (ER) antigen in sections of formalin-fixed, laborator the qualitative actocker or a Ventana automated slide stainer with Ventana detection kits and paramilliany reagents. CONFIRM anti-ER (SP1) is directed against an epitope present on himan ER alpha andiliary reagents. "OON frim and ER (Sire normal and neoplastic cells. CONFIRM anti-ER (SP1) is protein located in the nacieds of EN positive nonmal and neediction 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 OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K110215
Page 1 of 1