FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use (LINK) is intended for use in immunohistochemistry with EnVision™ FLEX +, High pH visualization kit together with the Autostainer Link 48 instrument to semiquantitatively detect human progesterone receptor in formalin fixed, paraffin embedded human breast carcinoma. This antibody labels progesterone receptor positive cells and is useful in the assessment of progesterone receptor status in human breast carcinomas.

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.

Device Description

Dako FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link) antibody is utilized to semi-quantitatively detect human progesterone receptor in formalin-fixed, paraffin-embedded (FFPE) human breast carcinoma. This product is pre-diluted and optimized for use with the Dako Autostainer Link 48 automated slide staining platform. Anti-PR, Clone PgR 636 is provided in liquid form in a buffer containing stabilizing protein and 0.015 mol/L sodium azide. The target concentration of Anti-PR, Clone PgR 636 is 0.5 ug/mL; the acceptable concentration range is 0.4 ug/mL to 0.6 ug/mL.

AI/ML Overview

The Dako FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link) antibody is intended for semi-quantitative detection of human progesterone receptor in formalin-fixed, paraffin-embedded (FFPE) human breast carcinoma using immunohistochemistry with the EnVision™ FLEX+, High pH visualization kit and the Dako Autostainer Link 48 automated slide staining platform. The device's clinical interpretation should be made by a qualified pathologist considering morphological studies, proper controls, patient's clinical history, and other diagnostic tests.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the device are not explicitly stated in terms of numerical thresholds for agreement values. However, the study aims to demonstrate "substantial equivalency" to the predicate device, the PR component of the Dako ER/PR pharmDx™ Kit. The reported performance metrics are:

Performance Metric	Reported Device Performance (Anti-PR, Clone PgR 636) ASCO/CAP vs. Predicate (ASCO/CAP)	Reported Device Performance (Anti-PR, Clone PgR 636) ASCO/CAP vs. Predicate (Allred)
Positive Percent Agreement (PPA)	99.1% (95% CI: 93.0-98.0)	95.8% (95% CI: 91.1-96.8)
Negative Percent Agreement (NPA)	93.3% (95% CI: 92.8-98.0)	93.1% (95% CI: 90.5-96.7)
Overall Percent Agreement (OPA)	96.2% (95% CI: 93.0-98.0)	94.5% (95% CI: 90.8-96.8)

Inter-Laboratory Reproducibility of Anti-PR, Clone PgR 636

Pairwise Comparison	Average Positive Percent Agreement	Average Negative Percent Agreement
Site 1 vs. Site 2	96.5%	95.8%
Site 1 vs. Site 3	99.2%	98.9%
Site 2 vs. Site 3	95.7%	94.7%

The repeated statement of "Study results demonstrate a substantial degree of equivalency to the predicate device" serves as the overarching acceptance criterion, which the provided agreement percentages are used to support.

2. Sample Size Used for the Test Set and Data Provenance

For the concordance study (comparison with the predicate device), the test set involved 236 breast carcinoma samples.
For the reproducibility study, 21 unique breast cancer specimens were used across three testing laboratories over five non-consecutive days, resulting in a total of 315 evaluations.

The document does not explicitly state the country of origin of the data. The studies appear to be retrospective, using formalin-fixed, paraffin-embedded (FFPE) human breast carcinoma samples.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not specify the number of experts or their qualifications who established the ground truth for the test set. It mentions that staining was "scored according to ASCO/CAP guidelines (≥1% cut-off)" and that "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." This implies that qualified pathologists were involved in the scoring, but the specific number and their experience levels are not provided.

4. Adjudication Method for the Test Set

The document does not explicitly state the adjudication method used for the test set. It refers to scoring "according to ASCO/CAP guidelines" and "Allred scoring guideline described in the package insert" for the predicate, which implies a standardized scoring protocol rather than a specific multi-reader adjudication method (e.g., 2+1, 3+1).

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

A MRMC comparative effectiveness study, in the sense of evaluating how human readers' performance improves with AI vs. without AI assistance, was not done. This device is an immunohistochemistry (IHC) assay, not an AI-assisted diagnostic tool.

However, the reproducibility study can be considered a multi-reader study as it involved testing in "three testing laboratories" over several days for inter-laboratory reproducibility, implying different readers/technicians performing and/or interpreting the tests.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

This is an IHC assay, not an algorithm, so a standalone performance study in the context of an algorithm's performance without human intervention is not applicable. The device (the antibody and associated staining platform) is inherently a tool for human interpretation by a pathologist.

7. Type of Ground Truth Used

The ground truth for the concordance study involved comparing the results of the new device (Anti-PR, Clone PgR 636) with those of the predicate device (PR component of the Dako ER/PR pharmDx™ Kit). The results from both were scored based on established guidelines (ASCO/CAP for the new device, and both ASCO/CAP and Allred for the predicate). This suggests a comparative "ground truth" established by an existing, FDA-cleared diagnostic method.

For the reproducibility study, the "ground truth" was based on repeated evaluations of "21 unique breast cancer specimens" scored according to ASCO/CAP guidelines. This would typically involve expert pathologist interpretation to establish the status of the samples.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" as this is not an AI/machine learning device. The antibody and assay development would involve internal validation and optimization, but these are not typically referred to as a "training set" in the context of regulatory submissions for IVD reagents.

9. How the Ground Truth for the Training Set Was Established

Since there is no explicit "training set" or "ground truth for the training set" in the context of this type of diagnostic reagent, this information is not applicable. The development of such an antibody assay primarily involves analytical validation (specificity, sensitivity, precision) and clinical validation (concordance, reproducibility) against established methods and clinical endpoints.

Summary

{0}------------------------------------------------

An Agilant Technolog

510(k) for Anti-PR, Clone PgR 636

K130861 DEC - 9 2013

510(k) Summary 5.

Traditional Premarket Notification Submission (510(k)) Summary Prepared in accordance with 21 CFR 807.92

5.1 Submitter Information

Sponsor name:	Dako North America, Inc.
Sponsor address:	6392 Via RealCarpinteria, CA 93013 USA
Sponsor Telephone:	805-566-6655
Sponsor Fax:	805-566-6688
Establishment Registration:	2022180

Contact person:	Jennifer Michelle ChambersMPA, MBA, CQA (ASQ)
Contact title:	Regulatory Affairs Specialist, Dako North America, Inc.
Email Direct (preferred):	jennifer.chambers@dako.com
Telephone Direct:	805-566-3036
Date Summary Prepared:	March 22, 2013

5.2 Device Name

Trade (proprietary):	FLEX Monoclonal Mouse Anti-Human ProgesteroneReceptor, Clone PgR 636, Ready-to-Use, (Link)
Common (usual):	Anti-PR, Clone PgR 636
Classification:	21 CFR 864.1860: Immunohistochemistry (IHC)Reagents and Kits (Class II)
FDA Device Code:	MXZ: Immunohistochemistry Assay, Antibody.Progesterone Receptor
Panel:	88 (Pathology)

5.3 Substantially Equivalent Predicate Device

Device Name:	PR component of the Dako ER/PR pharmDx™ Kit
Device 510(k):	K042884

{1}------------------------------------------------

Image /page/1/Picture/1 description: The image shows the logo for Dako, an Agilent Technologies company. The logo consists of a stylized flame-like symbol on the left, followed by the word "Dako" in bold, sans-serif font. Below "Dako" is the text "An Agilent Technologies Company" in a smaller, sans-serif font. The logo is black and white.

Table 3. Agreement between Anti-PR, Clone PgR 636 (ASCO/CAP) and Anti-PR Component of ER/PR pharmDx™ Kit (ASCO/CAP)

Anti-PR Component of ER/PR pharmDx™ Kit
		Positive	Negative	Total
Anti-PR,Clone PgR	Positive	115	8	123
636	Negative	1	112	113
	Total	116	120	236

Positive Percent Agreement = 99.1% (95% CI: 93.0-98.0) Negative Percent Agreement = 93.3% (95% CI: 92.8-98.0) Overall Percent Agreement = 96.2% (95% Cl: 93.0-98.0)

Table 4. Site 1 vs. Site 2 Inter Laboratory Reproducibility of Anti-PR, Clone PgR 636

	Site 1
		Positive	Negative	Total
Site 2	Positive	55	0	55
	Negative	4	46	50
	Total	59	46	105

Average Positive Percent Agreement = 96.5% Average Negative Percent Agreement = 95.8%

Table 5. Site 1 vs. Site 3 Inter Laboratory Reproducibility of Anti-PR, Clone PgR 636
---------------------------------------------------------------------------------------	--	--	--	--	--

		Site 1
		Positive	Negative	Total
Site 3	Positive	59	1	60
	Negative	0	45	45
	Total	59	46	105

Average Positive Percent Agreement = 99.2% Average Negative Percent Agreement = 98.9%

Table 6. Site 2 vs. Site 3 Inter Laboratory Reproducibility of Anti-PR, Clone PgR 636

	Site 2
Site 3		Positive	Negative	Total
	Positive	55	5	60
	Negative	0	45	45
	Total	55	50	105

Average Positive Percent Agreement = 95.7% Average Negative Percent Agreement = 94.7%

{2}------------------------------------------------

Image /page/2/Picture/0 description: The image shows the logo for Dako, an Agilent Technologies company. The logo consists of a stylized symbol resembling a drop or flame, followed by the word "Dako" in a bold, sans-serif font. Below "Dako" is the text "An Agilent Technologies Company" in a smaller, also sans-serif font. The logo is black and white.

Device Description 5.4

5.5 Intended Use

For in vitro diagnostic use.

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-touse (Link) is intended for use in immunohistochemistry with EnVision™ FLEX+, High pH visualization kit together with Autostainer Link 48 instrument to semi-quantitatively detect human progesterone receptor in formalin-fixed, paraffin-embedded (FFPE) human breast carcinoma. This antibody labels progesterone receptor-positive cells and is useful in the assessment of progesterone receptor status in human breast carcinomas.

Technological Characteristics 5.6

Dako FLEX Monoclonal Mouse Anti-Human Progesterone Receptor. Clone PoR 636. Ready-to-use (Link) Antibody IHC assav and the predicate PR component of the Dako ER/PR pharmDx™ Kit both specifically bind to PR proteins located in the cell nucleus of PR-expressing cells, and are optimized for use on formalin-fixed, paraffin-embedded (FFPE) tissues. Both products aid in the prognosis of breast carcinoma, both products have equivalent staining performance, and both products require similar detection chemistry principles for visualization of the product. The difference in visualization between the predicate device and Anti-PR, Clone PgR 636 has been clinically validated to ensure it does not introduce new issues of safety or effectiveness.

Performance Characteristics (Nonclinical) 5.7

Nonclinical Performance characteristics evaluated in support of the FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-use (Link) Antibody IHC assay include analytical specificity and precision. Study results demonstrate a substantial degree of equivalency to the predicate device.

{3}------------------------------------------------

Image /page/3/Picture/1 description: The image shows the logo for Dako, an Agilent Technologies company. The logo consists of a stylized symbol resembling a drop or flame, followed by the word "Dako" in bold, sans-serif font. Below "Dako" is the text "An Agilent Technologies Company" in a smaller font size.

5.8 Performance Characteristics (Clinical)

Clinical Performance characteristics evaluated in support of the FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-use (Link) Antibody IHC assay include concordance and reproducibility. Summaries of all performance testing are provided in the Executive Summary of this 510(k). Full reports of all performance testing are provided in the Performance Testing (Clinical) section of this 510(k).

Concordance: Anti-PR, Clone PgR 636 testing was performed with EnVision™ FLEX+ and scored according to ASCO/CAP quidelines (≥1% cut-off) (11). Anti-PR (Clone 1294) testing was performed using Dako ER/PR pharmDx™ Kit and scored using the Allred scoring guideline described in the package insert. The method comparison data are presented (Table 2). Using these respective scoring guidelines, Anti-PR, Clone PgR 636 was concordant with the PR antibody component of Dako ER/PR pharmDx™ Kit, exhibiting values for overall, positive and negative agreement of 94.5%, 95.8% and 93.1%, respectively. Both assays were compared when scored using the ASCO/CAP guidelines (Table 3). Study results demonstrate a substantial degree of equivalency to the predicate device.

Reproducibility: Anti-PR, Clone PgR 636 reproducibility testing was performed in three testing laboratories over five non-consecutive days on 21 unique breast cancer specimens, and scored according to ASCO/CAP guidelines (≥1% cut-off) for a total of 315 evaluations. Site to site reproducibility of the assay is detailed (Table 4, Table 5, and Table 6). The average positive and average negative percent agreement calculations support the highly reproducible results of the PR (PgR 636) assay when used for the determination of PR status in a clinical setting.

Anti-PR Component of ER/PR pharmDx™ Kit
Anti-PR,Clone PgR636		Positive	Negative	Total
	Positive	115	8	123
	Negative	5	108	113
	Total	120	116	236

Table 2. Agreement between Anti-PR, Clone PgR 636 (ASCO/CAP) and Anti-PR Component of ER/PR pharmDx™ Kit (Allred)

Positive Percent Agreement = 95.8% (95% Cl: 91.1-96.8) Negative Percent Agreement = 93.1% (95% CI: 90.5-96.7) Overall Percent Agreement = 94.5% (95% CI: 90.8-96.8)

{4}------------------------------------------------

Image /page/4/Picture/1 description: The image shows the logo for Dako, an Agilent Technologies company. The logo consists of a stylized black droplet shape to the left of the word "Dako" in a bold, sans-serif font. Below the word "Dako" is the text "An Agilent Technologies Company" in a smaller, sans-serif font.

Analytical specificity: Anti-PR, Clone PgR 636 immunoreactivity was tested on the recommended panel of normal tissues (Table 1). All tissues were formalin-fixed, paraffinembedded, and stained with Anti- PR, Clone PoR 636 according to the instructions in the package insert. Cytoplasmic staining was observed with Anti-PR, Clone PgR 636 in several different tissue elements including epithelium, stroma, interstitial cells and inflammatory cells. While cytoplasmic staining was observed, it is not considered diagnostic per the intended use of this antibody.

Precision: Serial sections from each of 12 different FFPE blocks of breast carcinoma, representing a dynamic range of PR expression, were collected for testing. Testing was performed as follows:

Intra-run precision: Following the standard EnVision™ FLEX+, High pH protocol, three sections from each tissue block were stained with Anti-PR, Clone PgR 636. Concurrently, one section from each block was stained with a negative control reagent.

Inter-run precision: Staining one section from each tissue block, the above procedure was repeated on five non-consecutive days. Concurrently, one section from each tissue block was stained with a negative control reagent.

Inter-instrument precision: Staining a total of three sections from each tissue block, the above procedure was performed on three different Autostainer instruments by three different operators. Concurrently, one slide from each tissue block was stained with a negative control reagent.

Precision experiments with Anti-PR, Clone PgR 636 yielded consistent results with intrarun, inter-run and inter-instrument testing. Consistent test conditions were maintained throughout the study, and reagents were stored at 2-8 ℃ between test runs.

{5}------------------------------------------------

Image /page/5/Picture/1 description: The image shows the logo for Dako, an Agilent Technologies company. The logo consists of a stylized symbol to the left of the word "Dako" in a bold, sans-serif font. Below the word "Dako" is the text "An Agilent Technologies Company" in a smaller font. The logo is simple and professional, and it is likely used on the company's website, marketing materials, and products.

Table 1. Summary of Anti-PR, Clone PgR 636 Normal Tissue Reactivity

Tissue Type (# tested)	Positive Tissue Elements
Adrenal (3)	1/3 cells in glomerulosa region (50%), nuclear1/3 cells in glomerulosa region (50%), nuclear
Bone marrow (3)	0/3
Breast (3)	2/3 Glandular epithelial cells (50-90%), nuclear
Cerebellum (3)	0/3
Cerebrum (3)	1/3 Meningial cells (100%), nuclear
Cervix (3)	3/3 Epithelial cells (50-90%), nuclear3/3 Stroma, including inflammatory cells (50%), nuclear
Colon (3)	1/3 Lymphoid/inflammatory cells (10%), nuclear1/3 Lympoid/inflammatory cells (10%), nuclear
Esophagus (3)	1/3 Stromal cells (50%), nuclear
Kidney (3)	3/3 Interstitial cells (1-5%), nuclear
Liver (3)	0/3
Lung (3)	2/3 Interstitial cells (1-10%), nuclear2/3 Inflammatory cells (1-10%), nuclear
Mesothelial cells (2)	0/2
Muscle, cardiac (3)	3/3 Myocytes (30%), peri-nuclear
Muscle, skeletal (3)	0/3
Nerve, peripheral (3)	0/3
Ovary (3)	3/3 Stromal cells (50-70%), nuclear
Pancreas (3)	2/3 Islets of Langerhans (50-90%), nuclear
Parathyroid (3)	3/3 Glandular epithelial cells (1-10%), nuclear
Pituitary (3)	3/3 Pituitary glandular cells (1-40%), nuclear
Prostate (3)	3/3 Stromal cells (30-80%), nuclear
Salivary gland (3)	3/3 Glandular epithelial cells (<1%-60%), nuclear
Skin (3)	0/3
Small intestine (3)	3/3 Stromal and inflammatory cells (30-50%), nuclear
Spleen (3)	0/3
Stomach (3)	1/3 Interstitial cells (20%), nuclear
Testis (3)	3/3 Interstitial cells (5-80%), nuclear
Thymus (3)	0/3
Thyroid (3)	0/3
Tonsil (3)	0/3
Uterus (2)	2/2 Glandular epithelial cells (100%), nuclear2/2 Myometrial stromal cells (100%), nuclear

In addition to the testing referenced above, additional nonclinical studies in support of the substantial equivalence of Anti-PR, Clone PgR 636 include lot-to-lot and stability testing. An additional study is referenced: Analytical sensitivity for antibody characterization, established for PgR 636 concentrate in K020023. Summaries of all performance testing are provided in the Executive Summary of this 510(k). Full reports of all performance testing are provided in the Performance Testing (Bench) section of this 510(k).

{6}------------------------------------------------

Image /page/6/Picture/0 description: The image shows the logo for Dako, which is "An Agilent Technologies Company". The logo consists of a stylized graphic to the left of the word "Dako". The text "An Agilent Technologies Company" is located below the word "Dako".

5.9 Conclusion

Based on the information provided in this premarket notification, Dako concludes that the FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-touse (Link) Antibody IHC assay is safe, effective, and substantially equivalent to the predicate device PR component of the Dako ER/PR pharmDx™ Kit in its indication for use, device design, materials, performance characteristics, and operational principles.

{7}------------------------------------------------

Image /page/7/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the seal is a stylized symbol that resembles a human figure embracing a globe.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 9, 2013

Dako North America, Inc Jennifer Michelle Chambers 6392 Via Real Carpinteria, CA 93013

Re: K130861

Trade/Device Name: Dako FLEX Monoclonal Mouse Anti-Human Progesterone Receptor,

Clone PgR 636, Ready-to-Use, (Link)

Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: II Product Code: MXZ Dated: November 8, 2013 Received: November 12, 2013

Dear Ms. Chambers:

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. 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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

{8}------------------------------------------------

Page 2-Ms. Chambers

: ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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/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 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/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Image /page/8/Picture/6 description: The image shows the text "Reena Balip -S" in a bold, sans-serif font. The words are arranged horizontally, with "Reena" on the left, followed by "Balip" in a slightly different style, and then "-S" on the right. The text is black against a white background, creating a clear contrast.

for

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

{9}------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K 1 3086 I

Device Name

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link)

Indications for Use (Describe) For in vitro diagnostic use.

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (LINK) is intended for use in immunohistochemistry with EnVision™ FLEX +, High pH visualization kit together with the Autostainer Link 48 instrument to semiquantitatively detect human progesterone receptor in formalin fixed, paraffin embedded human breast carcinoma. This antibody labels progesterone receptor positive cells and is useful in the assessment of progesterone receptor status in human breast carcinomas.

Type of Use (Select one or both, as applicable)

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 FDA USE ONLY Section and the mail of the mail of the mail of the mail of the mail of the mail of the mail of the mail of the mail of the mail of the mail of the mail of the mail of the ma : Concurrence of Center for Devices and Radiological Health (CDRH) (Signature,

Image /page/9/Picture/13 description: The image shows the text "Reena Philip -S" in a bold, sans-serif font. The word "Reena" is clearly legible, while "Philip" is stylized with a geometric pattern within the letters. The "-S" is smaller and positioned to the right of "Philip", completing the text string.

. . . . . ..

FORM FDA 3881 (9/13)

PSC Pablishing berriors (jul) 44 14723 用

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

Regulation Number and Section

§ 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.