(161 days)
Not Found
No
The device is an antibody used in an immunohistochemical assay, which is interpreted by a pathologist. There is no mention of automated image analysis or algorithmic interpretation.
No
The device is an in vitro diagnostic (IVD) intended to qualitatively identify human estrogen receptor. It is used as an aid in assessing patient response to hormonal therapy and prognosis/management of breast cancer, not for direct treatment.
Yes
The intended use explicitly states that the device is "intended for laboratory use to qualitatively identify by light microscopy human estrogen receptor in normal and/or pathological paraffin-embedded, formalin-fixed tissues" and "is indicated as an aid in assessing patient response to hormonal therapy and as an aid in the prognosis and management of breast cancer patients." These applications directly involve diagnosing, treating, or managing medical conditions.
No
The device is a monoclonal antibody, which is a biological reagent used in an immunohistochemical assay. It is a physical substance, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it is an "immunohistochemical (IHC) assay" and is "intended for laboratory use to qualitatively identify by light microscopy human estrogen receptor in normal and/or pathological paraffin-embedded, formalin-fixed tissues." This aligns with the definition of an IVD, which is used to examine specimens derived from the human body to provide information for the diagnosis, treatment, or prevention of disease.
- Specimen Type: It uses "paraffin-embedded, formalin-fixed tissues," which are specimens derived from the human body.
- Purpose: The purpose is to "qualitatively identify... human estrogen receptor," which is a biological marker. It is also indicated as an "aid in assessing patient response to hormonal therapy and as an aid in the prognosis and management of breast cancer patients." This information is used for clinical decision-making.
- Laboratory Use: The intended user is a "qualified pathologist" in a "laboratory setting."
- Comparison to Reference Method: The performance studies compare the device's results to a "reference DCC assay," which is a common practice for validating IVDs.
- Predicate Device: A predicate device (K993957; Dako estrogen receptor antibody) is listed, which is another IVD used for a similar purpose.
All these factors strongly indicate that the BioGenex Mouse Monoclonal Anti-Estrogen Receptor Antibody (Clone ER88) is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The BioGenex Mouse Monoclonal Anti-Estrogen Receptor Antibody (Clone ER88) is an immunohistochemical (IHC) assay and is intended for laboratory use to qualitatively identify by light microscopy human estrogen receptor in normal and/or pathological paraffin-embedded, formalin-fixed tissues. The ER88 antibody specifically binds to antigens located in the nucleus of cell populations that express estrogen receptor in normal and abnormal tissues. This antibody is indicated as an aid in assessing patient response to hormonal therapy and as an aid in the prognosis and management of breast cancer patients. 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.
BioGenex ER88 antibodies have been optimally manufactured for use with BioGenex Super Sensitive MultiLink Detection Systems with or without BioGenex Automated Staining Systems.
Product codes (comma separated list FDA assigned to the subject device)
MXZ
Device Description
BioGenex ER88 is a monoclonal antibody, which specifically binds to estrogen receptor antigen located in the nuclear region of a variety of normal and abnormal tissues. It is a mouse monoclonal anti-estrogen receptor antibody from mouse ascites fluid diluted in phosphate buffered saline pH 7.6 containing bovine serum albumin as carrier protein and 0.09% sodium azide as preservative. The antibody is available in concentrated (MU368-UC) as well as ready to use form (AM368-5M and AM368-10M). Refer to package insert for details.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Light microscopy
Anatomical Site
Human estrogen receptor in normal and/or pathological paraffin-embedded, formalin-fixed tissues, specifically human breast cancer.
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Laboratory use, 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
Specificity of Primary Antibody:
Sample size: A total of 88 formalin-fixed and paraffin-embedded tissues covering a wide range of normal human tissue types.
Data source: Not specified
Annotation protocol: Not specified, but involved testing with the BioGenex ER88 antibody using BioGenex Super Sensitive HRP Detection System.
Sensitivity:
Sample size: A total of 122 specimens.
Data source:
First batch of 29 specimens: DCC assay in the laboratory of the late Dr. William McGuire at the University of Texas Health Science Center at San Antonio, Texas. IHC staining done in the laboratory of Dr. Louis P. Pertschuk in the Department of Pathology, King's County Hospital, State University of New York, Health Science Center, Brooklyn, New York using detection reagents provided by BioGenex.
Second batch of 93 specimens: DCC assay in the laboratory of Dr. William Fricke (Genesee Hospital, Rochester, NY). Tissue blocks provided to BioGenex laboratories for slide preparation and IHC staining using BioGenex detection reagents.
Annotation protocol:
For DCC assays, results scored as positive using a cut-off value of ≥10 femtomoles/mg of protein.
For IHC staining, each resulting slide was read independently by two pathologists, who had no knowledge of any other laboratory or clinical data of the specimens. Scoring was based on percentage of cells with positive nuclear staining (Fitzgibbons PL, et al, 2000). Any trace of nuclear staining was counted as positive result (NIH Consensus Statement, 2000). The intensity of staining was not factored into the scoring system. A cut-off value of >10% of positive tumor cells was used to score a slide as positive or negative.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
-
Specificity of Primary Antibody
- Study Type: Specificity test
- Sample Size: 88 formalin-fixed and paraffin-embedded tissues
- Key Results: ER88 antibody demonstrated negative immunoreactivity with most normal human tissues. Positive immunoreactivity was observed with some normal tissues like the nuclei of acini and duct cells of mammary gland and myometrium and endometrium of uterus.
-
Reproducibility
- Study Type: Reproducibility
- Sample Size:
- Intra run: 10 slides of the same tissues within a single run.
- Inter run: Slides containing the same tissues over 10 different runs.
- Instrumental runs vs. manual runs: Ten slides each were stained manually and using BioGenex Automated Stainer for each of the tissues tested.
- Key Results:
- Intra run: No significant variation among the slides of the same tissue stained in the same run.
- Inter run: No significant variation among the slides of the same tissue stained in different runs.
- Instrumental runs vs. manual runs: No significant variation among the slides of the same tissue stained manually and in the automated process.
-
Sensitivity
- Study Type: Comparison between ER88 IHC and reference DCC assays
- Sample Size: 122 specimens
- Key Results: The overall binary concordance of ER88 IHC staining to ER DCC assay was 75% (92/122), with a 2-side 95% confidence interval of 68% - 83% (p
§ 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
·
FEB 2 8 2002
SUMMARY OF SAFETY AND EFFECTIVENESS INFORMATION
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.
GENERAL INFORMATION:
| Submitter: | BioGenex Laboratories, Inc.
4600 Norris Canyon Road
San Ramon, CA 94583
925-275-0550 (Tel)
925-275-0580 (Fax) |
|-----------------------------|---------------------------------------------------------------------------------------------------------------------------|
| Contact Persons: | Gurvinder S. Nanda, Ph.D.
Manager, Regulatory Affairs
925-543-1336 (Tel)
925-866-2525 (Fax) |
| | Jintao Chen, Ph.D.
Director, Operations
925-866-2568 (Tel)
925-866-2525 (Fax) |
| Date of Preparation: | January 30, 2002 |
| Device Generic Name: | Mouse Monoclonal Anti-Estrogen Receptor Antibody |
| Device Trade Name: | BioGenex Mouse Monoclonal Anti-Estrogen Receptor
Antibody (Clone ER88) |
| Device Classification Name: | Immunohistochemistry Reagents and Kits |
| Assigned 510(k) Number: | K013148 |
PREDICATE DEVICE:
The device is substantially equivalent to certain well-established, widely accepted reference laboratory methodology dextran-coated charcoal (DCC) technique which were common in use prior to May 28, 1976. The device is substantially equivalent in methodology to similar kit for estrogen receptor (Dako, K993957).
1
DESCRIPTION OF THE DEVICE:
BioGenex ER88 is a monoclonal antibody, which specifically binds to estrogen receptor antigen located in the nuclear region of a variety of normal and abnormal tissues. It is a mouse monoclonal anti-estrogen receptor antibody from mouse ascites fluid diluted in phosphate buffered saline pH 7.6 containing bovine serum albumin as carrier protein and 0.09% sodium azide as preservative. The antibody is available in concentrated (MU368-UC) as well as ready to use form (AM368-5M and AM368-10M). Refer to package insert for details.
INTENDED USE:
The BioGenex Mouse Monoclonal Anti-Estrogen Receptor Antibody (Clone ER88) is an immunohistochemical (IHC) assay and is intended for laboratory use to qualitatively identify by light microscopy human estrogen receptor in normal and/or pathological paraffin-embedded, formalin-fixed tissues. The ER88 antibody specifically binds to antigens located in the nucleus of cell populations that express estrogen receptor in normal and abnormal tissues. This antibody is indicated as an aid in assessing patient response to hormonal therapy and as an aid in the prognosis and management of breast cancer patients. 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.
BioGenex ER88 antibodies have been optimally manufactured for use with BioGenex Super Sensitive MultiLink Detection Systems with or without BioGenex Automated Staining Systems.
STATEMENT OF HOW TECHNOLOGICAL CHARACTERISTICS COMPARED TO SUBSTANTIAL EQUIVALENT DEVICE:
A table is provided below comparing the similarities and differences between the BioGenex device and the predicate Dako Device (K993957) to detect estrogen receptors in normal and or pathological tissues.
| | BioGenex
(New device-K013148) | Dako
(Predicate device K993957) |
|----------------------|-------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------|
| Clone | ER88 | 1D5 |
| Antibody | Mouse monoclonal | Mouse monoclonal |
| Immunoglobulin Class | Mouse IgG1, Kappa | Mouse IgG1, Kappa |
| Intended Use | Is intended for laboratory use
to qualitatively identify by
light microscopy human
estrogen receptor in normal | May be used in semi
quantitative detection of
human estrogen receptor in
tissue sections of human |
2
| | and/or pathological paraffin-
embedded, formalin-fixed
tissues. | breast cancer by
immunohistochemistry. |
|---------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indication | This antibody is indicated as
an aid in assessing patient
response to hormonal therapy
and as an aid in the prognosis
and management of breast
cancer patients. | This antibody is indicated as
an aid in assessing the likely
hood of response to therapy
as well as in prognosis and
management of breast cancer
patients. |
| Specificity | Human estrogen receptor in
formalin-fixed paraffin
embedded tissues. | Human estrogen receptor in
formalin-fixed paraffin
embedded tissues. |
| Total protein
concentration: | 10 mg/ml | 10 mg/ml |
| Storage | 2-8°C | 2-8°C |
| Application | For manual and automated
use | For manual and automated
use |
PERFORMANCE DATA:
1. Specificity of Primary Antibody
A total of 88 formalin-fixed and paraffin-embedded tissues covering a wide range of normal human tissue types were tested with the BioGenex ER88 antibody using BioGenex Super Sensitive HRP Detection System. In normal human tissues ER88 antibody demonstrated negative immunoreactivity with most tissues. However, positive immunoreactivity was observed with some normal tissues like the nuclei of acini and duct cells of mammary gland and myometrium and endometrium of uterus.
2. Reproducibility
- (a) Intra run (within-run) assay: The reproducibility of staining was determined by staining 10 slides of the same tissues within a single run. All slides were stained by the same individual using the same set of reagents for each of the tissues tested. Evaluation of the results indicates no significant variation among the slides of the same tissue stained in the same run.
- (b) Inter run (run-to-run) assay: The reproducibility between runs was determined by staining slides containing the same tissues over 10 different runs. Evaluation of the results indicates no significant variation among the slides of the same tissue stained in different runs.
- (c) Instrumental runs vs. manual runs: Ten slides each were stained with the antibody manually and using BioGenex Automated Stainer for each of the tissues tested. Tissue blocks were selected to demonstrate reproducibility over a wide
3
range of reactivity scale. The prediluted form of ER88 antibody was used for this study along with BioGenex Super Sensitive MultiLink Detection System with DAB as the substrate. Evaluation of the results indicates no significant variation among the slides of the same tissue stained manually and in the automated process.
3. Sensitivity
Comparison between ER88 IHC and reference DCC assays. The study was designed to use independent clinical specimens to establish the performance characteristics of ER88 antibody staining and its concordance with the reference methodology, dextrancharcoal coated (DCC) assay. The DCC assay is a biochemical assay and has been considered the gold standard for ER assay. More recently, immunohistochemistry (IHC) has become a popular method for such testing (Kell, D et al. 1993, Goussard, 1998; Ferrero-Pous, M et al. 2001).
A total of 122 specimens were used in this study. All the specimens were selected according to the following criteria: 1) fomalin-fixed and paraffin-embedded tissue sections were available; 2) each tissue was initially assayed for ER by DCC. No other selection criteria were employed. The study was conducted using two different batches of clinical specimens to include approximately 50% positive and negative cases.
The first batch of 29 specimens was assayed for DCC in the laboratory of the late Dr. William McGuire at the University of Texas Health Science Center at San Antonio, Texas. The DCC results were scored as positive using a cut-off value of ≥10 femtomoles/mg of protein. IHC staining of these slides was done in the laboratory of Dr. Louis P. Pertschuk in the Department of Pathology, King's County Hospital. State University of New York, Health Science Center, Brooklyn, New York using detection reagents provided by BioGenex.
The second batch of 93 specimens was assaved for DCC in the laboratory of Dr. William Fricke (Genesee Hospital, Rochester, NY). The DCC results were scored as positive or negative using a cut-off value of ≥10 femtomoles/mg of protein. The tissue blocks were provided to BioGenex laboratories for slide preparation and IHC staining using BioGenex detection reagents.
For both the studies, each resulting slide was read independently by two pathologists, who have no knowledge of any other laboratory or clinical data of the specimens. The scoring was based on percentage of cells with positive nuclear staining (Fitzgibbons PL, et al, 2000). Any trace of nuclear staining was counted as positive result (NIH Consensus Statement, 2000). The intensity of staining was not factored into the scoring system. A cut-off value of >10% of positive tumor cells was used to score a slide as positive or negative.
4
The overall binary concordance of ER88 IHC staining to ER DCC assay was 75% (92/122), with a 2-side 95% confidence interval of 68% - 83% (p