(635 days)
No
The device is a monoclonal antibody used for immunohistochemistry, a laboratory staining technique. The analysis and interpretation are performed by a qualified pathologist using light microscopy. There is no mention of automated image analysis or algorithmic interpretation.
No
Explanation: This device is intended for laboratory use to identify estrogen receptor (ER) antigen to aid in the management, prognosis, and prediction of therapy outcome for breast cancer, not for treating a disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device "is indicated as an aid in the management, prognosis and predication of therapy outcome of breast cancer," and that "The clinical interpretation of any staining or its absence should be complemented by morphological studies... and other diagnostic tests by qualified pathologist." These phrases clearly indicate its role in diagnosis and clinical decision-making.
No
The device is a monoclonal antibody used for immunohistochemistry, which is a biological reagent, not a software-only medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the antibody is for "laboratory use to qualitatively identify estrogen receptor (ER) antigen in sections of formalin fixed, paraffin embedded breast cancer tissue by immunohistochemistry methods." It is also indicated as "an aid in the management, prognosis and predication of therapy outcome of breast cancer." This clearly describes a test performed in vitro (outside the body) on a biological specimen (tissue) to provide information for medical diagnosis and management.
- Device Description: The description details a "semi-quantitative immunohistochemical (IHC) assay" used to identify ER expression in human breast cancer tissue. This is a common type of in vitro diagnostic test.
- Performance Studies: The document includes detailed descriptions of performance studies, including a clinical outcome study, precision studies, reproducibility studies, and an inter-platform comparison study. These types of studies are required for IVD devices to demonstrate their analytical and clinical performance.
- Key Metrics: The document reports key metrics such as Sensitivity, Specificity, PPV, NPV, and various agreement percentages. These are standard metrics used to evaluate the performance of IVD devices.
- Predicate Device: The mention of a predicate device (K060227) further confirms that this device is being submitted for regulatory review as an IVD, likely through the 510(k) pathway, which requires comparison to a legally marketed predicate device.
All of these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Estrogen Receptor Clone 6F11 (ER 6F11) Mouse Monoclonal antibody is intended for laboratory use to qualitatively identify estrogen receptor (ER) antigen in sections of formalin fixed, paraffin embedded breast cancer tissue by immunohistochemistry methods. Estrogen Receptor Clone 6F11 specifically binds to the ER antigen located in the nucleus of ER positive normal and neoplastic cells.
Estrogen Receptor Clone 6F1 I is indicated as an aid in the management, prognosis and predication of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by qualified pathologist.
Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ and the Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, Novocastra™ are optimized for use on the Leica Biosystems Bond III staining platform using the Bond Polymer Refine Detection Kit.
Product codes
MYA
Device Description
Estrogen Receptor Clone 6F11 is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant. This antibody is utilized to perform a semi-quantitative immunohistochemical (IHC) assay to identify estrogen receptor (ER) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination.
Estrogen Receptor Clone 6F11 primary antibody is provided in two formats, a Bond™ Ready-to-Use format (product code PA0151 (7mL) and PA0009 (30 mL)) and a concentrated liquid format (product code NCL-L-ER-6F11 (1mL) and is optimally diluted for use on the automated Bond System (Bond III ) in combination with Bond Polymer Refine Detection kit.
Total protein concentration for Estrogen Receptor clone 6F11 is approximately 3.8 g/L. The immunoglobulin concentration is approximately 75 mg/L.
The Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, Novocastra" is recommended for use at a dilution of 1 in 50 when diluted in Bond Antibody Diluent (AR9352).
The Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ is a tissue culture supernatant prepared at a working immunoglobulin concentration of 0.88 µg/mL. It is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Light microscope
Anatomical Site
Breast cancer tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Laboratory use by a qualified pathologist.
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
Clinical Outcome Study (Calgary Cohort):
Study used a retrospective Calgary-based patient cohort (n=532) composed of breast cancer patients diagnosed between 1985 and 2000.
Allred scoring method for inter- and intra-observer reproducibility.
Ligand-binding assay (LBA) was used as the gold standard for sensitivity, specificity, PPV, and NPV calculations.
Progression on tamoxifen was also used as a gold standard for LBA calculations.
Precision Results:
Within Run Precision Study (intra assay - single instrument): 108 test data points with Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ (Lot 21825), 1 test slide with negative control antibody and 1 assay Control Slide.
Within Instrument Precision Study (inter assay - single Instrument): 321 test data points with Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ (Lot 21825), 3 test slides with negative control antibody and 3 assay Control Slide.
Between Run Precision Study (inter assay - day-to-day - single instrument): 180 test data points with Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ (Lot 21825), 1 test slide with negative control antibody and 1 assay Control Site.
Between Laboratory Precision Study (site-to-site - inter assay - multiple instruments): 101 test data points with Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ (Lot 21825), 1 test slide with negative control antibody and 1 assay Control Slide at 3 investigational sites (Sites A, B and C).
Lot to Lot Precision Study: 100 test data points with Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™, 3 test slides with negative control antibody and 3 assay Control Slide using three (3) independently manufactured reagent lots.
Between Observer Precision Study (Ready-to-Use): 20 whole section breast cancer cases consisting of 5x Positive (Strong Intensity Expression), 5x Positive (Medium Intensity Expression), 5x Positive (Weak Intensity Expression), and 5x Negative Profile Breast Carcinoma cases. Evaluated between 3 observers at 1 investigational site.
Between Observer Precision Study (Liquid Concentrate): 20 whole section breast cancer cases consisting of 5x Positive (Strong Intensity Expression), 5x Positive (Medium Intensity Expression), 5x Positive (Weak Intensity Expression), and 5x Negative Profile Breast Carcinoma cases. Evaluated between 3 observers at 1 investigational site.
Reproducibility Results (whole tissue section testing):
Inter-Site Reproducibility (Ready-to-Use): Test cohort consisted of 18 cases. Tested at 3 investigational sites (Sites A, B and C) over 5 non-consecutive days (Day1, Day3, Day 5), with each site staining a full set of cases on each day. This provided 9 replicates of 18 cases.
Lot to Lot Precision Study (Ready-to-Use): Test cohort consisted of 18 cases. Tested at a single investigational site using three (3) independently manufactured reagent lots. This provided 3 replicates of each slide.
Inter-Site Reproducibility (Liquid Concentrate): Test cohort consisted of 18 cases. Tested at 3 investigational sites (Sites A, B and C) over 5 non-consecutive days (Day1, Day3, Day 5), with each site staining a full set of cases on each day. This provided 9 replicates of 18 cases.
Lot to Lot Precision Study (Liquid Concentrate): Test cohort consisted of 18 cases. Tested at a single investigational site using three (3) independently manufactured reagent lots. This provided 3 replicates of each slide.
Inter-Platform Comparison Study:
The total cohort for the Inter-Platform comparison study was three hundred and six (306) invasive breast cancer specimens obtained from clinical archives, formalin fixed, and paraffin embedded whole tissue sections. Screeners were blinded to the test used. An additional 452 cases were assessed in an attempt to enrich the cohort.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
1. Clinical Outcome Study (Calgary Cohort):
- Study Type: Retrospective clinical outcome study.
- Sample Size: n=532 breast cancer patients (a subset of n=473 for univariate analysis, and n=363 for multivariate analysis).
- Key Results:
- Reproducibility (Cohen's Kappa for Allred scoring):
- Inter-observer kappa for ER (Leica platform): Observers 1 and 2 (kappa=0.67), Observers 1 and 3 (kappa=0.75), Observers 2 and 3 (kappa=0.83). Indicated "almost perfect agreement".
- Intra-observer kappa for Observer 1: kappa=0.91 ("almost perfect agreement").
- Univariate Kaplan-Meier Survival Analysis: Showed significant difference (p
- Reproducibility (Cohen's Kappa for Allred scoring):
§ 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/0 description: The image shows the logo for Leica Biosystems. The logo features the word "Leica" in a stylized, cursive font, with a thick, flowing line extending from the "L" to underline the entire word. Below "Leica" is the word "BIOSYSTEMS" in a bold, sans-serif font, with the letters evenly spaced.
MAY 1 9 2014
1 510(k) Summary
Traditional Premarket Notification Submission 510(k) Summary Prepared in accordance with 21 CFR 807.92
Assigned 510(k) number US K122556
2 Sponsor Name and Address
Leica Biosystems Newcastle, Ltd Balliol Business Park West Newcastle Upon Tyne, NE 12 8EW United Kingdom Establishment Registration: 3004859032
3 Contact
Barbara-Ann Conway-Myers, Ph.D. Senior Regulatory Affairs Specialist bacm@LeicaBiosystems.com 312-269-7205
4 Statement Prepared
July 8, 2012
5 Summary Revised:
April 15, 2014
Device Name б
| Trade (proprietary): | Estrogen Receptor Clone 6F11 |
|---|---|
| Common (usual): | Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for BondTM |
| Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, NovocastraTM | |
| Classification: | 21 CFR § 864.1869: Immunohistochemistry (IHC) |
| Reagents and Kits (Class II) | |
| FDA Device Code: | MYA |
1
Image /page/1/Picture/0 description: The image shows the logo for Leica Biosystems. The logo consists of the word "Leica" in a stylized, bold font, with a swooping line extending from the left side of the "L" to underneath the "a". Below the word "Leica", in a smaller, sans-serif font, is the word "BIOSYSTEMS". The logo is black and is set against a white background.
Panel:
88 (Pathology)
7 Substantially Equivalent Predicate Device
| Device Name: | Estrogen Receptor Clone 6F11, formerly named Vision BioSystems Estrogen Receptor Clone 6F11 (ER 6F11) (change due to re-branding) |
|---|---|
| Device 510(k): | · K060227 |
8 Device Description
Estrogen Receptor Clone 6F11 is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant. This antibody is utilized to perform a semi-quantitative immunohistochemical (IHC) assay to identify estrogen receptor (ER) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination.
Estrogen Receptor Clone 6F11 primary antibody is provided in two formats, a Bond™ Ready-to-Use format (product code PA0151 (7mL) and PA0009 (30 mL)) and a concentrated liquid format (product code NCL-L-ER-6F11 (1mL) and is optimally diluted for use on the automated Bond System (Bond III ) in combination with Bond Polymer Refine Detection kit.
Total protein concentration for Estrogen Receptor clone 6F11 is approximately 3.8 g/L. The immunoglobulin concentration is approximately 75 mg/L.
The Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, Novocastra" is recommended for use at a dilution of 1 in 50 when diluted in Bond Antibody Diluent (AR9352).
The Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ is a tissue culture supernatant prepared at a working immunoglobulin concentration of 0.88 µg/mL. It is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative.
9 Test Principle
Immunohistochemical staining techniques allow for the visualization of antigens via the sequential application of a specific antibody to the antigen (primary antibody, ER), a secondary antibody to the primary antibody and an enzyme complex with a chromogenic substrate with interposed washing steps. The enzymatic activation of the chromogen results in a visible reaction product at the antigen site. The specimen may then be counterstained and coverslipped. Results are interpreted using a light microscope and aid in the differential diagnosis of pathophysiological processes, which may or may not be associated with a particular antigen.
2
Image /page/2/Picture/0 description: The image shows the logo for Leica Biosystems. The word "Leica" is written in a stylized, cursive font. Below "Leica" is the word "BIOSYSTEMS" written in a sans-serif font. The logo is in black and white.
A schematic diagram of the immunohistochemical staining technique using a polymer detection system is shown in figure 1 and described below.
Image /page/2/Picture/2 description: The image shows a diagram of a DAB staining process. The DAB molecules are shown as a chain of brown circles. The DAB molecules are binding to a secondary antibody, which is bound to a primary antibody. The primary antibody is bound to a tissue antigen.
Figure 1. Schematic diagram of the immunohistochemical staining technique using a polymer detection system to detect the primary antibody.
Estrogen Receptor Clone 6F11 is recommended for use in an immunohistochemical procedure, which allows the qualitative identification by light microscopy of antigens in sections of formalin-fixed, paraffin-embedded tissue, via sequential steps with interposed washing steps. Prior to staining, endogenous peroxidase activity is blocked and sections are subjected to epitope retrieval. As indicated in figure 1, the section is subsequently incubated with the mouse primary antibody that binds with the human tissue antigen. A polymeric enzyme-conjugated secondary antibody that recognizes mouse immunoglobulins is used to detect the primary antibody. Sections are further incubated with the substrate/chromogen, 3,3' - diaminobenzidine (DAB), and DAB Substrate Buffer. Reaction with the peroxidase produces a visible brown precipitate at the antigen site. Sections are counterstained with hematoxylin and coverslipped. Results are interpreted using a light microscope.
3
Image /page/3/Picture/0 description: The image shows the logo for Leica Biosystems. The word "Leica" is written in a stylized, cursive font, with a distinctive loop in the "L" and a dot over the "i". Below "Leica", in a smaller, sans-serif font, is the word "BIOSYSTEMS" in all capital letters. The logo is black against a white background.
10 Intended Use
For in vitro diagnostic use
Estrogen Receptor Clone 6F11 (ER 6F11) Mouse Monoclonal antibody is intended for laboratory use to qualitatively identify estrogen receptor (ER) antigen in sections of formalin fixed, paraffin embedded breast cancer tissue by immunohistochemistry method. Estrogen Receptor Clone 6F11 specifically binds to the ER antigen located in the nucleus of ER positive normal and neoplastic cells.
Estrogen Receptor Clone 6F11 is indicated as an aid in the management, prognosis and predication of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.
Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ and Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, Novocastra "" are optimized for use on the Leica Biosystems Bond III staining platform using the Bond Polymer Refine Detection kit.
11 Performance Characteristics (Clinical)
Clinical Outcome Study (Calgary Cohort)
The Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ (PA0151) on the Bond III was tested in an independent clinical outcome study. In summary, the study used a retrospective Calgary-based patient cohort (n=532) composed of breast cancer patients diagnosed between 1985 and 2000, who were treated with primary adjuvant tamoxifen regardless of their ER and PR status. This cohort possesses several unique characteristics that lend to this study, including: it has greater than 5 years of follow-up; it was enriched for events to increase its statistical power; it contains ER negative patients so as to remove treatment selection bias.
To assess differences between methods in the study, the following statistical methods were evaluated ' and the outcomes described:
- The Cohen's Kappa statistic to quantify the ease of reproducibility of Allred scoring method (Inter- and Intra-Observer).
Results indicated that Inter-observer kappa for the Leica platform showed almost perfect agreement for ER, with x=0.67 between Observers 1 and 2, к=0.75 between Observers 1 and 3, and а к=0.83 between
4
Image /page/4/Picture/0 description: The image shows the logo for Leica Biosystems. The word "Leica" is written in a stylized, cursive font. Below "Leica" is the word "BIOSYSTEMS" written in a sans-serif, block letter font. The logo is black and white.
Observers 2 and 3. Slides were also rescored by Observer 1 three months after the original scoring and intra-observer kappa was calculated with almost perfect agreement of k=0.91.
- Univariate Kaplan-Meier and Multivariate Cox survival analysis using the Allred cutpoint for hormone receptor positivity to dichotomize patients into survival groups.
The univariate outcome is shown in figure 2.
Image /page/4/Figure/4 description: This image is a survival plot comparing disease-free survival probability over time in months for two groups, ER- and ER+. The ER- group has a significantly lower survival probability than the ER+ group, with the ER- group dropping to around 0.50 probability at 60 months, while the ER+ group remains above 0.75. The plot indicates a p-value of less than 0.0001 and a hazard ratio (HR) of 0.24 (0.14-0.43), with a total sample size of n=473.
Figure 2: Univariate Analysis for the Leica test Device
5
Image /page/5/Picture/0 description: The image shows the logo for Leica Biosystems. The logo features the word "Leica" in a stylized, bold font, with a curved line extending from the bottom of the "L" to the "a". Below "Leica", the word "BIOSYSTEMS" is written in a smaller, sans-serif font. The entire logo is in black against a white background.
| Leica Device (n=363) | |||
|---|---|---|---|
| HR | 95% CI | p-value | |
| ER Status | 0.39 | (0.19-0.78) | 0.008 |
| Lymph Node Status | 3.18 | (1.88-5.37) | 10% tumour staining). Reproducibility studies have shown that for cases around the cut-off (1-10% tumour staining), a single pathologist has reproducibly estimated a similar percentage of cells staining between the three replicate slides. When all three pathologist percentage of cells staining scores are compared, it has shown that some variation in the number of cells estimated exists. This shows the limitations of a subjective method based on estimation alone. |
In addition, small differences in the percentage of cells stained and then estimated by the same pathologist may be due to tumour heterogeneity. Multiple sections from each tissue block are required to perform reproducibility studies, with this process resulting in different cells being examined between each section. Small foci of tumour will invariably cut in/out of the tissue section and result in differences in interpretation. This phenomenon has been widely published and the concept is most effectively demonstrated by the micro-dissection of sentinel node tumour micro-metastases analysis (Weaver 2010).
Based on acceptance and approval of the Test Device Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond 111, this device is now considered the Reference Standard Test for the further Inter-Platform Comparison Studies.
14 Inter-Platform Comparison Study
An inter-platform comparison study was performed at three independent US based testing facilities. Comparative data between the reference standard device Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ on the Bond III and Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, NovocastraTM on the Bond III.
Blinding and randomization was used throughout the evaluation to reduce bias. Screeners were blinded to the test used.
The sample types (specimens) used in clinical evaluation were whole tissue sections, formalin fixed, and paraffin embedded invasive breast cancer cases. The specimens utilized were obtained from clinical archives, representative of the intended population, samples appropriately handled in the clinical environment, and met all local and national institutional review board (IRB) ethical approval for use in clinical evaluation studies.
Positive procedural controls were performed to validate assay performance. Procedural controls were not used for statistical analysis.
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Image /page/25/Picture/0 description: The image shows the logo for Leica Biosystems. The word "Leica" is written in a stylized, bold font. Below "Leica" is the word "BIOSYSTEMS" written in a smaller, sans-serif font. The logo is black and white.
Negative controls were performed on the same tissues as the test article. The negative controls were not used for statistical analysis.
14.1 Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, Novocastra™ on the Bond III (Test Device)
Inter-Platform comparison study results for Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, Novocastra™ on the Bond III compared against the reference standard test using the primary evaluation method are shown below.
| Reference Standard Test | |||
|---|---|---|---|
| Positive | Negative | ||
| NCL-L-ER-6F11 | |||
| (Concentrate) Bond III | Positive | 241 | 6 |
| Negative | 4 | 55 | |
| Overall Percent Agreement (95% CI) | 96.73% (94.07-98.42%) | ||
| Positive Percent Agreement (95% CI) | 98.37% (95.87-99.55) | ||
| Negative Percent Agreement (95% CI) | 90.16% (79.81-96.30) |
Based on the results, all documented evidence supports substantial equivalence between the both the concentrated and RTU formats of ER 6F11 on the Bond III.
14.2 Inter-Platform Comparison Study Summary
The total cohort included for the Inter-Platform comparison study was three hundred and six (306) invasive breast cancer specimens.
A requirement set by FDA for the cohort to include a minimum of 10% of test cases that express estrogen receptor around the cut off (1-10%), when assessed by the reference standard device, was not met. The total overall percentage of cases in this category was 7.5% (23/306). Assessment of an additional 452 cases was undertaken in an attempt to enrich the cohort to 10%.
Recent publications (Hicks DH, Zhang Z, et al), in which 1700 consecutive invasive breast cancer patients were assessed for ER status, indicated that only 2% of cases expressed estrogen in the 1-10% range. This indicates that these tumours are not common and that the 7.5% of cases assessed within this cohort is representative of almost 4 times the normal population.
Additionally, differences in the percentage of cells stained and then estimated by the same pathologist between test devices may be due to tumour heterogeneity. Multiple sections from each tissue block are required to perform comparison studies, with this process resulting in different cells being examined between each section. Foci of tumour will invariably cut in/out of the tissue section and result in differences in interpretation. This phenomenon has been widely
26
Image /page/26/Picture/0 description: The image shows the logo for Leica Biosystems. The word "Leica" is written in a stylized, bold font. Below "Leica" is the word "BIOSYSTEMS" written in a smaller, sans-serif font. The logo is black and white.
published and the concept is most effectively demonstrated by the micro-dissection of sentinel node tumour micro-metastases analysis (Weaver 2010).
In addition to the evaluation method and in keeping with standard pathological practice, all aspects of staining quality were assessed and reported for each case, i.e., staining intensity, proportion of cells staining, background staining, tissue morphology, staining of benign ductal cells, stromal cells, endothelial cells and lymphocytes.
Stability Summary 15
Stability studies were performed using three independently manufactured lots of Estrogen Receptor Clone 6F11 for the different formats of the product listed below.
- Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ -- 7 ml PA0151 .
- Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ 30 mL PA0009 .
- Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, Novocastra™ 1 mL NCL-L-. ER-6F11
Testing was performed on breast cancer tissue sections that expressed estrogen receptor at a high (3), medium (2), low (1) and negative (0) intensity (Intensity Score) and on normal breast tissue.
Acceptance criteria is based on; Test case passes if the Intensity Score and the Proportion Score (≥ 1% of turnour cell nuclei staining = Positive; 1% of tumour
cell nuclei staining
= Positive; Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, Novocastra™M
Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry Reagents and Kits Regulatory Class: II Product Code: MYA Dated: April 8, 2014 Received: April 10, 2014
Dear Dr. Conway-Myers:
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. Iisting 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 Parts 801 and 809); medical device reporting (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 Part 820); and if applicable, the
30
Page 2-Dr. Conway-Myers
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours,
Reena Philip -S
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
31
Indications for Use
510(k) Number (if known) K122556
Device Name
Estrogen Receptor Clone 6F11 (ER 6F11)
· Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™;
· Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, NovocastraTM
Indications for Use (Describe)
Estrogen Receptor Clone 6F11 (ER 6F11) Mouse Monoclonal antibody is intended for laboratory use to qualitatively identify estrogen receptor (ER) antigen in sections of formalin fixed, paraffin embedded breast cancer tissue by immunohistochemistry methods. Estrogen Receptor Clone 6F11 specifically binds to the ER antigen located in the nucleus of ER positive normal and neoplastic cells.
Estrogen Receptor Clone 6F1 I is indicated as an aid in the management, prognosis and predication of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by qualified pathologist.
Estrogen Receptor Clone 6F11 Ready-to-Use Primary Antibody for Bond™ and the Estrogen Receptor Clone 6F11 Liquid Concentrate Primary Antibody, Novocastra™ are optimized for use on the Leica Biosystems Bond III staining platform using the Bond Polymer Refine Detection Kit.
Type of Use (Select one or both, as applicable)
2 Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FOR FDA USE ONLY ON LINE OF A
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
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This section applies only to requirements of the Paperwork Reduction Act of 1995.
*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW."
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."