IMAGEN RESPIRATORY SCREEN by DAKO DIAGNOSTICS LTD.

The IMAGENTM Respiratory Screen is a qualitative indirect immunofluorescence test for the detection of Respiratory Syncytial Virus, Influenza A virus, Parainfluenza virus type 3 and Adenovirus directly in respiratory specimens and Respiratory Syncytial Virus, Influenza A and B virus. Parainfluenza virus types 1, 2 and 3 and Adenovirus in cell culture monolayers.

Device Description

The test consists of the following reagents: a Screening reagent, a Negative control reagent, a Fluorescein Isothiocyanate (FITC) Conjugate reagent, Mounting fluid, and Positive and Negative Control slides. It is a two-step direct immunofluorescence staining method.

AI/ML Overview

This document describes the IMAGENTM Respiratory Screen, a qualitative indirect immunofluorescence test for detecting various respiratory viruses. The information provided focuses on its performance characteristics and safety.

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific performance metrics (e.g., sensitivity, specificity thresholds). Instead, it describes performance characteristics established through external clinical evaluations against a predicate device (Bartels Viral Respiratory Screening and Identification Kit) and standard viral isolation reference methods.

The reported device performance is presented as a summary of claims that have been established (or are ongoing).

Acceptance Criteria (Implied)	Reported Device Performance
Directly in respiratory specimens:
Detection of Respiratory Syncytial virus (RSV)	Claims established
Detection of Influenza A virus	Claims established
Detection of Parainfluenza virus type 3	Claims established
Detection of Adenovirus	Claims established
Detection of Influenza B virus	Trials ongoing to collect adequate data
Detection of Parainfluenza virus type 1	Trials ongoing to collect adequate data
Detection of Parainfluenza virus type 2	Trials ongoing to collect adequate data
In cell culture isolates:
Detection of Respiratory Syncytial virus (RSV)	Data submitted to support claims
Detection of Influenza A virus	Data submitted to support claims
Detection of Influenza B virus	Data submitted to support claims
Detection of Parainfluenza virus type 1	Data submitted to support claims
Detection of Parainfluenza virus type 2	Data submitted to support claims
Detection of Parainfluenza virus type 3	Data submitted to support claims
Detection of Adenovirus	Data submitted to support claims

Missing critical information includes:

Specific sensitivity and specificity values (or other relevant metrics) that were considered acceptable.
The statistical methods used to determine if the performance met any implicit criteria.

Study Information

The document provides limited details on the specific studies conducted:

Sample size used for the test set and the data provenance: The document does not specify the sample size used for the external clinical evaluation (test set). It also does not mention the country of origin of the data or whether the studies were retrospective or prospective. It only states "external clinical evaluation."
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: This information is not provided.
Adjudication method for the test set: The document does not describe any adjudication method.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done: An MRMC study is not mentioned. The evaluation was against a predicate device and standard viral isolation reference methods, not described as a comparative effectiveness study with human readers.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: The IMAGENTM Respiratory Screen is a diagnostic kit (reagents) used by qualified technicians. Its performance is inherently linked to human interpretation, so a purely standalone (algorithm-only) performance is not applicable in the traditional sense for this type of test. Its "standalone" performance would be the performance of the assay itself when processed and interpreted by a technician, which is what the clinical evaluation would assess.
The type of ground truth used: The ground truth for the test set was established using "the Bartels Viral Respiratory Screening and Identification Kit and standard viral isolation reference methods." This implies that viral isolation (a microbiological gold standard) was the primary ground truth, with the Bartels kit potentially used as a comparator or secondary reference.
The sample size for the training set: This information is not provided. As an immunofluorescence assay kit, it doesn't typically have a "training set" in the machine learning sense. The "training" of the product would involve its development, antibody selection, and optimization, not a data-driven training set like an AI algorithm.
How the ground truth for the training set was established: Not applicable in the context of an immunofluorescence test kit, as there's no "training set" in the AI sense. The development of the kit would rely on known positive and negative viral samples for reagent specificity and sensitivity optimization.

Summary

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SUMMARY OF SAFETY AND EFFECTIVENESS ડ.

DEC 2 6 1996

a Screening reagent; a pool of purified mouse monoclonal antibodies each of which has i) individual specificity for either Respiratory Synctial virus, Influenza A and B virus, Parainfluenza types 1,2 and 3 and Adenovirus.
a Negative control reagent; pooled mouse monoclonal antibodies with no anti-viral ii) activity .
a Fluorescein Isothiocyanate (FITC) Conjugate reagent; FITC conjugated F(ab')2 iii) fragment of rabbit anti-mouse immunoglobulins
Mounting fluid; containing a photobleaching inhibitor in glycerol iv)
Positive and Negative Control slides; fourteen well combined positive and negative v) control slides. Each slide consists of seven wells containing acetone-fixed cells infected with either RSV, Influenza A or B virus, Parainfluenza virus type 1, 2 or 3 or Adenovirus (one well specific for each virus) and seven wells containing acetone fixed uninfected cells (negative control wells).

IMAGENTM Respiratory Screen is a two-step direct immunofluorescence staining method. The Screening reagent utilises a pool of mouse monoclonal antibodies to bind specifically to either Respiratory Syncytial Virus, Influenza A or B virus, Parainfluenza virus types 1, 2 or 3 or Adenovirus. The FITC conjugate reagent is used to detect any Screening reagent antibody which has bound to virus present in the respiratory specimen or cell culture monolayer. The Negative control reagent contains mouse monoclonal antibodies with no reactivity with any viral antigen or any antigen likely to be present in a respiratory specimen and is used to monitor the specificity of the stain. The respiratory virus present can be specifically identified using individual IMAGENTM reagents.

Performance characteristics have been established by external clinical evaluation against the Bartels Viral Respiratory Screening and Identification Kit and standard viral isolation reference methods used for screening for the presence of respiratory viruses. (Exhibit F) and by evaluation of cross-reactivity (Exhibit G). Currently sufficient data has only been collected to establish claims for the identification of Respiratory Syncytial virus, Influenza A virus, Parainfluenza virus type 3 and Adenovirus directly in respiratory specimens. Trials are ongoing to collect adequate data to establish the outstanding claims for Influenza B virus and Parainfluenza virus types 1 and 2 for direct specimen testing. Data is submitted to support claims for the identification of all seven viruses (Respiratory Synctial virus, Influenza A and B virus, Parainfluenza virus types 1, 2 and 3 and Adenovirus) in cell culture isolates.

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IMAGENTM Respiratory Screen is intended for use in laboratories where qualified technicians are familiar with routine indirect immunofluorescence testing for microbiological diagnosis. However specific quality control information regarding the validity of test results is included in the Product Insert, to facilitate reliable and reproducible results and minimise the occurrence of false positive or false negative results. Procedures include the use of positive and negative control slides, a negative control reagent and specifications for acceptable results. Technical references and a Technical Services phone number are provided to aid the user in further trouble-shooting.

The IMAGENTM Respiratory Screen is similar in use and technology to Bartel's Viral Respiratory Screening and Identification Kit, which is already in commercial distribution in the n.2.

The product insert contains a list of safety and technical precautions which should be followed to ensure safe and effective use of the IMAGENTM Respiratory Screen diagnostic test. This includes advice on handling and disposal of clinical specimens as though potentially infectious. Suggested precautions include the wearing of disposable gloves when handling clinical specimens and infected cells and washing of hands immediately after completion of the test. In addition the test should be carried out in a designated work area where eating, drinking, smoking, preparation and storage of food and application of cosmetics are not carried out. Materials should not be pipetted by mouth.

The following safety information about reagents is given in the Directions for Use :-

The IMAGENTN Respiratory Screen reagents contain 15mmol/L sodium azide which is a POISON. Sodium azide may react with copper and lead plumbing systems to form explosive metal azides. Always dispose of azide-containing materials by washing with large quantities of water.

Evans blue dye is present in the FTTC reagent. This may be carcinogenic and contact with the skin should be avoided

Care should be taken when using the mounting fluid as it may cause skin irritation. Skin should be flushed with water if contact occurs.

Further information regarding the safety and effectiveness of IMAGEN™ Respiratory Screen will be made available within 30 days of request by any person. This information excludes confidential patient information and proprietary manufacturing procedures pertinent to this Dr Elisabeth Johnson-Proctor, device. Please contact:

Head of Quality and Regulatory Affairs, DAKO Diagnostics Limited, Denmark House, Angel Drove, Ely, Cambridgeshire, CB7 4ET, UK. Fax (353) 668989 Phone (353) 669911

Signature: Elsbeth Jms-Port Date: 9 April 1996

Regulation Number and Section

§ 866.3330 Influenza virus serological reagents.

(a)
Identification. Influenza virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to influenza in serum. The identification aids in the diagnosis of influenza (flu) and provides epidemiological information on influenza. Influenza is an acute respiratory tract disease, which is often epidemic.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.