Medical Devices

Letter of Authorization: Emergency Use of Focus Diagnostics Simplexa™ Influenza A H1N1 (2009) Test

October 16, 2009

John G. R. Hurrell, Ph.D.
Vice President and General Manager
Focus Diagnostics, Inc.
11331 Valley View Street
Cypress, CA 90630

Dear Dr. Hurrell:

This letter is in response to your request that the Food and Drug Administration (FDA) issue an Emergency Use Authorization (EUA) for emergency use of the Focus Diagnostics Simplexa™ Influenza A H1N1 (2009) (Simplexa™ Inf A H1N1-09)¹ for the diagnosis of 2009 H1N1 influenza virus infection, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 360bbb-3) by CLIA High Complexity Laboratories, which are laboratories certified under the Clinical Laboratory Improvement Amendments of 1988, 42 U.S.C. § 263a, to perform high complexity tests.

On April 26, 2009, pursuant to section 564(b)(1)(C) of the Act (21 U.S.C. § 360bbb-3(b)(1)(C)), the Secretary of the Department of Health and Human Services (HHS) determined that there is a public health emergency under 42 U.S.C. § 247d that affects, or has a significant potential to affect, national security, and that involves a specified biological, chemical, radiological, or nuclear agent or agents, or a specified disease or condition that may be attributable to such an agent or agents -- in this case, 2009 H1N1 influenza virus.² Pursuant to section 564(b) of the Act (21 U.S.C. § 360bbb-3(b)), and on the basis of such determination, the Secretary of HHS then declared an emergency justifying the authorization of the emergency use of certain in vitro diagnostics for the detection of 2009 H1N1 influenza virus, subject to the terms of any authorization issued under 21 U.S.C. § 360bbb-3(a).

Having concluded that the criteria for issuance of this authorization under section 564(c) of the Act (21 U.S.C. § 360bbb-3(c)) are met, I am authorizing the emergency use of the Focus Diagnostics Simplexa™ Inf A H1N1-09 for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection , subject to the terms of this authorization .

I. Criteria for Issuance of Authorization

I have concluded that the emergency use of the Simplexa™ Inf A H1N1-09 for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection meets the criteria for issuance of an authorization und er section 564(c) of the Act, because I have concluded that:

The recently isolated 2009 H1N1 influenza virus can cause influenza, a serious or life threatening disease or condition to humans infected by this virus;
Based on the totality of scientific evidence available to FDA, it is reasonable to believe that the Simplexa™ Inf A H1N1-09 may be effective for the diagnosis of 2009 H1N1 influenza virus infection, and that the known and potential benefits of the Simplexa™ Inf A H1N1-09 when used in the diagnosis of 2009 H1N1 influenza virus infection, outweigh the known and potential risks of such product; and
There is no adequate, approved, and available alternative to the emergency use of the Simplexa™ Inf A H1N1-09 for the diagnosis of 2009 H1N1 influenza virus infection.³

Therefore, I have concluded that the emergency use of the Simplexa™ Inf A H1N1-09 for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection meets the above criteria for issuance of an authorization.

II. Scope of Authorization

I have concluded, pursuant to section 564(d)(1) of the Act, that the scope of this authorization is limited to the use of the authorized Simplexa™ Inf A H1N1-09 for the diagnosis of 2009 H1N1 influenza virus infection in individuals with signs and symptoms of respiratory infection.

The Authorized Simplexa™ Inf A H1N1-09

The Focus Diagnostics Simplexa™ Inf A H1N1-09 is a real-time RT-PCR assaythat utilizes a fluorescent probe-primer for use on the 3M Integrated Cycler for the in vitro qualitative detection of 2009 H1N1 influenza viral RNA in nasopharyngeal swabs (NPS), nasal swabs (NS), and nasal aspirates (NA) from patients with signs and symptoms of respiratory infection.The assay is composed of two principal steps: (1) extraction of RNA from patient specimens, (2) a bi-functional fluorescent probe-primer is used together with a reverse primer to amplify a specific target (for each analyte and internal control).

The Simplexa™ Inf A H1N1-09 kit includes the following primer sets:

FLUA detects a well-conserved region of the matrix gene from influenza A viruses in both seasonal human influenza A virus and 2009 H1N1 influenza virus.
H1N1 specifically detects the 2009 H1N1 influenza virus strain’s hemagglutinin gene. The FLUA and H1N1 reactions are multiplexed and are performed in the same well.

The Simplexa™ Inf A H1N1-09 kit also includes control materials :

Armored RNA Internal Control (AR IC) : An internal positive control is included to confirm the absence of PCR inhibition.
External Positive Control : Inactivated 2009 H1N1 Virus .
External Negative Control : Nuclease free water.

The Simplexa™ Inf A H1N1-09 requires the following hardware with corresponding software:

Roche MagNA Pure LC: Nucleic acid extraction instrument.
3M Integrated Cycler: PCR amplification instrument.

The Simplexa™ Inf A H1N1-09 requires the use of the following additional reagent kit:

MagNA Pure LC Total Nucleic Acid Isolation Kit (Roche Cat. No 3038505001)

The above Simplexa™ Inf A H1N1-09, when labeled consistently with the attached labeling, as may be revised with written permission of FDA, is authorized to be distributed to CLIA High Complexity Laboratories under this EUA, despite the fact that it does not meet certain requirements otherwise required by federal law.

The above described Simplexa™ Inf A H1N1-09 is authorized to be accompanied by the following information pertaining to the emergency use, which are authorized to be made available to health care providers and patients:

Fact Sheet For Healthcare Providers: Interpreting Focus Diagnostics Simplexa™ Influenza A H1N1 (2009) Test Results
Fact Sheet For Patients: Understanding The Focus Diagnostics Simplexa™ Influenza A H1N1 (2009) Test Results

As described in section IV below, Focus Diagnostics and CLIA High Complexity Laboratories are also authorized to make available additional information relating to the emergency use of the authorized Simplexa™ Inf A H1N1-09 that is consistent with, and does not exceed, the terms of this letter of authorization.

I have concluded, pursuant to section 564(d)(2) of the Act, that it is reasonable to believe that the known and potential benefits of the authorized Simplexa™ Inf A H1N1-09 in the specified population, when used for diagnosis of 2009 H1N1 influenza virus infection, outweigh the known and potential risks of such product.

I have concluded, pursuant to section 564(d)(3) of the Act, based on the totality of scientific evidence available to FDA, that it is reasonable to believe that the authorized Simplexa™ Inf A H1N1-09 may be effective in the diagnosis of 2009 H1N1 influenza virus infection pursuant to section 564(c)(2)(A) of the Act. FDA has reviewed the scientific information available including the information supporting the conclusions described in Section I above, and concludes that the authorized Simplexa™ Inf A H1N1-09 when used to diagnose 2009 H1N1 influenza virus infection in the specified population, meets the criteria set forth in section 564(c) of the Act concerning safety and potential effectiveness.

The emergency use of the authorized Simplexa™ Inf A H1N1-09 under this EUA must be consistent with, and may not exceed, the terms of this letter, including the scope and the conditions of authorization set forth below. Subject to the terms of this EUA and under the circumstances set forth in the Secretary of HHS's determination under section 564(b)(1)(C) described above and the Secretary of HHS's corresponding declaration under section 564(b)(1), the Simplexa™ Inf A H1N1-09 described above is authorized to diagnose 2009 H1N1 influenza virus infection in human individuals with signs and symptoms of respiratory infection.

This EUA will cease to be effective when the declaration of emergency is terminated under section 564(b)(2) of the Act or when the EUA is revoked under section 564(g) of the Act.

III. Waiver of Certain Requirements

I am waiving the following requirements for the Simplexa™ Inf A H1N1-09 during the duration of this emergency use authorization:

Current good manufacturing practice requirements, including the quality system requirements under 21 CFR Part 820 with respect to the design, manufacture, packaging, labeling, storage, and distribution of the Simplexa™ Inf A H1N1-09.
Labeling requirements for cleared, approved, or investigational devices, including labeling requirements under 21 CFR 809.10 and 809.30, except for the intended use statement (21 CFR 809.10(a)(2), (b)(2)), adequate directions for use (21 U.S.C. 352(f)), (21 CFR 809.10(b)(5) and (8)), any appropriate limitations on the use of the device including information required under 21 CFR 809.10(a)(4), and any available information regarding performance of the device, including requirements under 21 CFR 809.10(b)(12).

IV. Conditions of Authorization

Pursuant to section 564 of the Act, I am establishing the following conditions on this authorization:

Focus Diagnostics

Focus Diagnostics will distribute the Simplexa™ Inf A H1N1-09 with the attached labeling only to CLIA High Complexity Laboratories.
Focus Diagnostics will provide to the CLIA High Complexity Laboratories the authorized Simplexa™ Inf A H1N1-09 Fact Sheet for Healthcare Providers and the authorized Simplexa™ Inf A H1N1-09 Fact Sheet for Patients.
Focus Diagnostics will make available on its Web site the authorized Simplexa™ Inf A H1N1-09 Fact Sheet for Healthcare Providers and the authorized Simplexa™ Inf A H1N1-09 Fact Sheet for Patients.
Focus Diagnostics will ensure that the state and/or local public health authority(ies) are informed of this EUA, including the terms and conditions herein.
All advertising and promotional descriptive printed matter relating to the use of the Focus Diagnostics Simplexa™ Inf A H1N1-09 shall be consistent with the Fact Sheets and attached labeling, as well as the terms set forth in this EUA and other requirements set forth in the Act and FDA regulations.
All advertising and promotional descriptive printed matter relating to the use of the Focus Diagnostics Simplexa™ Inf A H1N1-09 shall clearly and conspicuously state that:
- This test has not been FDA cleared or approved,
- This test has been authorized by FDA under an Emergency Use Authorization,
- This test is only authorized for the duration of the declaration of emergency under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), and
- The declaration of emergency will expire on April 26, 2010, unless it is terminated or revoked sooner or renewed.
No advertising or promotional descriptive printed matter relating to the use of the Focus Diagnostics Simplexa™ Inf A H1N1-09 may represent or suggest that this test is safe or effective for the diagnosis of 2009 H1N1 influenza virus.
Focus Diagnostics will ensure CLIA High Complexity Laboratories have a process in place for reporting test results to health care providers and federal, state and/or local public health authorities, as appropriate.
Focus Diagnostics will track adverse events and report to the FDA as required under 21 CFR part 803.
Through a process of inventory control, Focus Diagnostics will maintain records of device usage.
Focus Diagnostics will collect information on the performance of the assay, and report to FDA any suspected occurrence of false positive or false negative results of which Focus Diagnostics becomes aware.

CLIA High Complexity Laboratories

CLIA High Complexity Laboratories will include with reports of the results of the Simplexa™ Inf A H1N1-09 the authorized fact sheets for health care providers and the authorized fact sheet for patients.
CLIA High Complexity Laboratories will perform the assay on a 3M Integrated Cycler as part of the Microfluidic Molecular System.
CLIA High Complexity Laboratories will have a process in place for reporting test results to health care providers and federal, state and/or local public health authorities, as appropriate.
CLIA High Complexity Laboratories will collect information on the performance of the assay, and report to Focus Diagnostics any suspected occurrence of false positive or false negative results of which CLIA High Complexity Laboratories become aware.

Focus Diagnostics and CLIA High Complexity Laboratories

Focus Diagnostics is authorized to make available additional information relating to the emergency use of the authorized Simplexa™ Inf A H1N1-09 that is consistent with, and does not exceed, the terms of this letter of authorization.
Only Focus Diagnostics may request changes to the authorized Fact Sheet for Healthcare Providers or the authorized Simplexa™ Inf A H1N1-09 Fact Sheet for Patients. Such requests will be made by contacting FDA concerning FDA review and approval.
Focus Diagnostics will ensure that any records associated with this EUA are maintained until notified by FDA. Such records will be made available to FDA for inspection upon request.

The emergency use of the authorized Simplexa™ Inf A H1N1-09 as described in this letter of authorization must comply with the conditions above and all other terms of this authorization.

V. Duration of Authorization

This EUA will be effective until the declaration of emergency is terminated under section 564(b)(2) of the Act or the EUA is revoked under section 564(g) of the Act.

Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs

¹ For ease of reference, this letter will use the term “Simplexa™ Inf A H1N1-09.”

² Memorandum, Determination Pursuant to § 564 of the Federal Food, Drug, and Cosmetic Act (April 26, 2009).

³ No other criteria of issuance have been prescribed by regulation under section 564(c)(4) of the Act.