BOND Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) , Novocastra Concentrated Liquid Mouse Monoclonal Antibody

K183102 · Leica Biosystems Newcastle, Limited · MXZ · Dec 7, 2018 · Hematology

Device Facts

• Record ID: K183102
• Device Name: BOND Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) , Novocastra Concentrated Liquid Mouse Monoclonal Antibody
• Applicant: Leica Biosystems Newcastle, Limited
• Product Code: MXZ · Hematology
• Decision Date: Dec 7, 2018
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 864.1860
• Device Class: Class 2

Indications for Use

Ready-to-Use Format Progesterone Receptor (16) monoclonal antibody is intended to be used for the qualitative identification by light microscopy of human progesterone receptor (PR) in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX system. Progesterone Receptor Clone (16) [PR (16)] specifically binds to the PR antigen located in the nucleus of PR positive normal and neoplastic cells. PR (16) is indicated as an aid in the management, prognosis and prediction 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. Concentrated Liquid Antibody Format. Progesterone Receptor (PGR) Clone 16 monoclonal antibody is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. PGR Clone 16 specifically binds to the PGR antigen located in the nucleus of PGR positive normal and neoplastic cells. PGR Clone 16 is indicated as an aid in the management, prognosis and prediction 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's clinical history and other diagnostic tests by a qualified pathologist.

Device Story

BOND™ RTU and Concentrated Liquid Mouse Monoclonal Antibody (Clone 16) are immunohistochemistry (IHC) reagents; used for qualitative identification of progesterone receptor (PR) in formalin-fixed, paraffin-embedded (FFPE) tissue sections. RTU format is optimized for automated BOND-MAX system; concentrated format is for manual or automated use. Pathologists use light microscopy to visualize nuclear staining in normal and neoplastic cells. Results serve as an aid in breast cancer management, prognosis, and therapy prediction. Clinical interpretation requires correlation with patient history, morphology, and other diagnostic tests.

Clinical Evidence

No clinical data. Verification and validation were limited to bench testing, including staining verification, EMC testing, hardware/firmware progression, and system integration/regression testing to ensure the modified hardware and software maintained performance equivalent to the predicate.

Technological Characteristics

Mouse monoclonal antibody (Clone 16) targeting human progesterone receptor. Reagents provided in Ready-to-Use (RTU) format for automated BOND-MAX system or as concentrated liquid. Principle of operation is immunohistochemical staining for light microscopy visualization of nuclear antigens in FFPE tissue.

Indications for Use

Indicated for qualitative identification of human progesterone receptor (PR) in formalin-fixed, paraffin-embedded breast tissue as an aid in management, prognosis, and prediction of therapy outcome for breast cancer patients.

Regulatory Classification

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.

Special Controls

(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.

Submission Summary (Full Text)

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SPECIAL 510(K): DEVICE MODIFICATION OIR DECISION MEMORANDUM

510(k) Number: K183102

This 510(k) submission contains information/data on modifications made to the applicant’s own class II or class I devices requiring 510(k). The following items are present and acceptable:

1. The name and 510(k) number of the applicant’s previously cleared device.

K171753: BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™)

2. Applicant’s statement that the INDICATION/INTENDED USE of the modified device as described in its labeling HAS NOT CHANGED along with the proposed labeling which includes instructions for use, package labeling, and, if available, advertisements or promotional materials (labeling changes are permitted as long as they do not affect the intended use).

3. A description of the device MODIFICATION(S), including clearly labeled diagrams, engineering drawings, photographs, user’s and/or service manuals in sufficient detail to demonstrate that the FUNDAMENTAL SCIENTIFIC TECHNOLOGY of the modified device has not changed.

This change was for

- Replacement of the slide staining assembly (SSA) printed wiring assembly (PWA) and its associated embedded firmware due to microprocessor obsolescence,
- BOND software update from version 5.1 to 6.0.

No changes have been made to the BOND IHC F protocol that is used on the BOND MAX instrument and no change has been made to the reagent for the BOND Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™) assay.

The BOND IHC F protocol has been verified to remain consistent by (a) not changing the data supplied to the BOND Application and (b) showing that the data passed to the instrument remains identical to that under the previous approved software releases versions 4.1, 5.0 and 5.1.

Verification and validation activities are performed for every change to BOND Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and the BOND-MAX instrument. The verification and validation procedures, methods and acceptance criteria for product changes remain the same as those performed for the predicate device, K171753.

4. Comparison Information (similarities and differences) to applicant’s legally marketed predicate device including device name, intended use, physical characteristics, quality control and antibody manufacturing, labeling as well as software, are in the table below.

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| Item | K183102 (Subject Device) | K171753 (Predicate Device) |
| --- | --- | --- |
| Device Name | BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™) | Same |
| Intended Use / Indications for Use | Ready-to-Use Format
Progesterone Receptor (16) monoclonal antibody is intended to be used for the qualitative identification by light microscopy of human progesterone receptor (PR) in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX system. Progesterone Receptor Clone (16) [PR (16)] specifically binds to the PR antigen located in the nucleus of PR positive normal and neoplastic cells.
PR (16) is indicated as an aid in the management, prognosis and prediction 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.
Concentrated Liquid Antibody Format.
Progesterone Receptor (PGR) Clone 16 monoclonal antibody is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. PGR Clone 16 specifically binds to the PGR antigen located in the nucleus of PGR positive normal and neoplastic cells.
PGR Clone 16 is indicated as an aid in the management, prognosis and prediction 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. | Same |
| RTU Reagent | Progesterone Receptor (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant, and supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative. | Same |

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| | Total Volume = 7 mL
Total Protein Concentration: 10 mg/mL
Antibody Concentration: ≥ 1 mg/L | |
| --- | --- | --- |
| Concentrated AB Reagent | NCL-L-PGR-312 is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative.
Total Protein Concentration: Batch Specific | Same |
| Clone, Immunogen, Specificity, Subclass (both formats) | Clone: 16
Immunogen: Prokaryotic recombinant protein corresponding to the N-terminal region of the A form of the human progesterone receptor
Specificity: Human progesterone receptor
Subclass: IgG1 | Same |
| Technology | Immunohistochemistry | Same |
| Tissue Type | formalin-fixed, paraffin-embedded breast cancer tissue | Same |
| Staining Pattern | Nuclear | Same |
| Platform | RTU: BOND-MAX | Same |
| Staining Protocol | BOND IHC F | Same |
| Slide Staining Assembly (SSA) Printed Wiring Assembly (PWA) | Replacement of the SSA PWA and its associated embedded firmware due to microprocessor obsolescence | Original SSA / PWA |
| BOND Software | Version 6.0 | Version 5.1 |

5. A Design Control Activities Summary which includes:

a) Identification of Risk Analysis method(s) used to assess the impact of the modification on the device and its components, and the results of the analysis
b) Based on the Risk Analysis, an identification of the verification and/or validation activities required, including methods or tests used and acceptance criteria to be applied

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Risk assessments for the SSA PWA changes and BOND software v5.1 to v6.0 changes were performed to assess the impact of the modifications on the device by identifying risks, their possible causes, and appropriate control mechanisms. The Risk Analyses took into account device hazards associated with the intended use of the device. No additional hazards, no additional causes, and no required additional controls were identified. No adverse events or reportable incidents have been associated with the device.

The following studies were performed to verify and validate for the SSA PWA changes:

- Staining Verification and Validation
- EMC Testing
- Overall Hardware and Software Verification
- Hardware Progression Verification
- Firmware Progression Verification
- System Integration Verification
- System Regression Verification
- Upgrade Utility Verification

The following studies were performed to verify and validate for the update of BOND software from v5.1 to v6.0:

- Staining Verification and Validation
- Software Verification

For each test, acceptance criteria were identified and observed results were compared to expected results. All acceptance criteria were met and all tests passed.

The labeling for this modified subject device has been reviewed to verify that the indication/intended use for the device is unaffected by the modification. In addition, the applicant’s description of the particular modification(s) and the comparative information between the modified and unmodified devices demonstrate that the fundamental scientific technology has not changed. The applicant has provided the design control information as specified in The New 510(k) Paradigm and on this basis, I recommend the device be determined substantially equivalent to the previously cleared (or their preamendment) device.

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