Monoclonal Rabbit Anti-Human Estrogen Receptor a (ER a) antibody, Clone SP1, may be used in the semi-quantitative detection of human estrogen receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer by immunohistochemistry. The information gained by this assay can aid in assessing the likelihood of response to therapy as well as in the prognosis and management of breast cancer patients.

Clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.

Device Description

Dako Monoclonal Rabbit Anti-Human Estrogen Receptor a antibody, Clone SP1 is a semiquantitative immunohistochemical (IHC) kit assay to identify estrogen receptor (ER) expression in normal and neoplastic tissues routinely processed and paraffin-embedded.

AI/ML Overview

The provided text describes the Dako Monoclonal Rabbit Anti-Human Estrogen Receptor a antibody, Clone SP1, an immunohistochemical (IHC) assay. The document is a 510(k) summary and associated FDA correspondence, which focuses on demonstrating substantial equivalence to a predicate device rather than presenting specific acceptance criteria and detailed study results for a novel device.

Therefore, much of the requested information regarding detailed acceptance criteria, specific performance metrics, sample sizes, ground truth establishment, and MRMC studies is not explicitly present in the provided text.

Here's an analysis of what can be extracted based on the document's content:

1. Table of Acceptance Criteria and Reported Device Performance:

The document states that "Performance characteristics evaluated for the Estrogen Receptor Clone SP1 IHC assay include results on analytical specificity and sensitivity, precision, reproducibility and method comparison testing." It then states: "Results of all testing conducted substantial equivalence to the predicate device listed above."

This implies that the acceptance criterion was achieving substantial equivalence to the predicate device, especially across these performance characteristics. However, specific numerical targets for these characteristics are not provided.

Acceptance Criteria (Implied)	Reported Device Performance (Implied)
Demonstrate substantial equivalence to predicate device (Monoclonal Mouse ER 1D5/ER-2-123 in Dako ER/PR pharmDx™ Kit) for:	Substantial equivalence achieved.
- Analytical specificity	Met
- Analytical sensitivity	Met
- Precision	Met
- Reproducibility	Met
- Method comparison	Met

2. Sample size used for the test set and data provenance:

Sample size: The document does not specify the sample size (number of cases or samples) used for the testing that established substantial equivalence.
Data provenance: Not explicitly stated. The document refers to "testing conducted," but provides no details on the origin, retrospective, or prospective nature of the data.

3. Number of experts used to establish the ground truth for the test set and their qualifications:

Number of experts: Not specified.
Qualifications: "Evaluations should be made within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist." This indicates that pathologists are involved in interpretation but does not detail their role in establishing a ground truth for testing.

4. Adjudication method for the test set:

Not specified.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, and its effect size:

An MRMC study is not mentioned. The focus is on the device's performance against a predicate device, not direct human reader improvement with or without the device.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

This device is an IHC antibody, which is a reagent used in a laboratory setting for manual or automated staining, subsequently interpreted by a pathologist. It is not an "algorithm" in the sense of AI. Therefore, the concept of "standalone performance" for an algorithm without a human-in-the-loop is not applicable in this context. The assay itself requires human interpretation.

7. The type of ground truth used:

The document implies that the ground truth for comparing the new device against the predicate device would be based on the established accuracy of the predicate device and potentially agreement with clinical and morphological findings. The statement "Clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls" suggests that the ultimate ground truth incorporates pathological and clinical evaluation, but the specific method for establishing a gold standard for the comparison study is not detailed.

8. The sample size for the training set:

This device is a biological reagent (antibody), not a machine learning algorithm that requires a "training set" in the conventional sense. Therefore, the concept of a training set size is not applicable.

9. How the ground truth for the training set was established:

As explained above, the concept of a training set is not applicable to this type of device.

In summary:

The provided document is a regulatory submission focused on demonstrating substantial equivalence of a new IHC reagent to an existing one. It does not provide the detailed study design, acceptance criteria, specific performance metrics, or ground truth establishment methods that would be expected for a novel diagnostic algorithm or AI device as the questions imply. The study described is primarily a comparative study to establish equivalency to a predicate, rather than a de novo performance validation with detailed acceptance criteria.

Summary

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MAY - 8 2009

510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92 (c).

The assigned 510(k) number is: K081286

Submitter:	Dako North America, Inc.6392 Via RealCarpinteria, CA 93013PH. 805.566.6655 FX. 805.566.0866Establishment registration number: 2022180
Contact:	Kelly MillerManager, Regulatory AffairsPH. 805.566.6655 ext. 5330Fax: 805.566.0866
Date Summary Prepared:	April 8, 2009
Device Name(s):	Monoclonal Rabbit Anti-Human Estrogen Receptor a antibody,Clone SP1(Code M3634)
Device Classification:	Class II (21 CFR 864.1860)
Predicate Device:	Monoclonal Mouse ER 1D5/ER-2-123 in the Dako ER/PRpharmDx™ Kit (K042884)

Device Description:

Intended Use:

For in vitro diagnostic use.

Clinical interpretation of any positive staining or its absence should be complemented by morphological and histological studies with proper controls. Evaluations should be made

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within the context of the patient's clinical history and other diagnostic tests by a qualified pahtologist.

Substantial Equivalence:

Dako Estrogen Receptor Clone SP1 immunohistochemical assay is substantially equivalent to Monoclonal Mouse ER 1D5/ER-2-123 in the Dako ER/PR pharmDx™ Kit. Both products specifically bind to estrogen receptor proteins located in the nuclei of cells, these products require similar detection chemistry principles for visualization of the product, and both aid in the prognosis of breast carcinoma.

Performance Characteristics:

Performance characteristics evaluated for the Estrogen Receptor Clone SP1 IHC assay include results on analytical specificity and sensitivity, precision, reproducibility and method comparison testing. Results of all testing conducted substantial equivalence to the predicate device listed above.

Based on the information provided in this premarket notification, Dako concludes that Monoclonal Rabbit Anti-Estrogen Receptor a, Clone SP1 is substantially equivalent to the predicate device and is safe and effective for its intended use.

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Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services, USA. The logo features a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES, USA" is arranged in a circular pattern around the eagle. The logo is black and white and appears to be a scanned image.

Public Health Service

Food and Drug Administration 2098 Gailher Road Rockville MD 20850

MAY - 8 2009

Dako North America, Inc. c/o Kelly Miller Manager RA 6392 Via Real Carpinteria, CA 93013

Re: K081286

Trade/Device Name: Dako Monoclonal Rabbit Anti-Human Estrogen Receptor, Clone SP1 Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: MYA Dated: May 4, 2009 Received: May 5, 2009

Dear Ms. Miller:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter

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Page 2 - Ms. Kelly Miller

will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Viro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (240) 276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. For more information regarding the reporting of adverse events, please go to http://www.fda.gov/cdrh/mdr/.

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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Mana M. Chan

Maria Chan, PhD Division Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): K081286

Device Name: Dako Monoclonal Rabbit Estrogen Receptor a, Clone SP1

Indications For Use:

For in vitro diagnostic use.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use J (Per 21 CFR 801.109)

OR
Maris M Chan

Division Sign-Off

Over-The-Counter Use (Per 21 CFR 801.110)

IVD Use_______________________________________________________________________________________________________________________________________________________________________ (Per 21 CFR 801.119) Office of in Vitro Dlagnostic Device Evaluation and Safety

Proprietary and confidential

8-Apr-09

510kl

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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.