• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Medical Devices

  • Print
  • Share
  • E-mail

Letter of Authorization: Emergency Use of Prodesse ProFlu-ST Influenza A assay for the diagnosis of 2009 H1N1 Influenza virus infection

The information previously contained on these webpages were authorized under the 2009 H1N1 Influenza Emergency Use Authorizations (EUAs). As of June 23, 2010, the EUAs have been terminated and this information is no longer current.

October 27, 2009

Thomas M. Shannon
President and Chief Executive Officer
Prodesse, Inc.
W229 N1870 Westwood Drive
Waukesha, WI 53186

Dear Mr. Shannon:

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 Prodesse ProFlu-ST Influenza A Subtyping Assay for the diagnosis of 2009 H1N1 influenza virus infection aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results in individuals who are diagnosed with influenza A by currently available FDA-cleared or authorized devices, 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.1 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 the Department of Health and Human Services then declared an emergency justifying the authorization of the emergency use of certain in vitro diagnostics for the detection of Swine Influenza A (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 Prodesse ProFlu-ST Influenza A Subtyping Assay (Prodesse ProFlu-ST Assay)2 for the diagnosis of 2009 H1N1 influenza virus infection aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results in individuals who are diagnosed with influenza A by currently available FDA-cleared or authorized devices, subject to the terms of this authorization.

I. Criteria for Issuance of Authorization

I have concluded that the emergency use of the Prodesse ProFlu-ST Assay for the diagnosis of 2009 H1N1 influenza virus infection aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results in individuals who are diagnosed with influenza A by currently available FDA-cleared or authorized devices, meets the criteria for issuance of an authorization under section 564(c) of the Act, because I have concluded that:

  • The 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 Prodesse ProFlu-ST Assay may be effective for the diagnosis of 2009 H1N1 influenza virus infection, and that the known and potential benefits of the Prodesse ProFlu-ST Assay, 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 Prodesse ProFlu-ST Assay for the diagnosis of 2009 H1N1 influenza virus infection.3,4

Therefore, I have concluded that the emergency use of the Prodesse ProFlu-ST Assay for the diagnosis of 2009 H1N1 influenza virus infection aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results in individuals who are diagnosed with influenza A by currently available FDA-cleared or authorized devices 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 Prodesse ProFlu-ST Assay for the diagnosis of 2009 H1N1 influenza virus infection aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results in individuals who are diagnosed with influenza A by currently available FDA-cleared or authorized devices.

The Authorized Prodesse ProFlu-ST Assay:

The Prodesse ProFlu-ST Assay is a multiplex real-time RT-PCR assay that utilizes fluorogenic hydrolysis (Taqman) probes for use on the Cepheid SmartCycler II instrument for the in vitro qualitative detection of 2009 H1N1 influenza viral RNA aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results in nasopharyngeal swabs (NPS) from patients who are diagnosed with influenza A by currently available FDA-cleared or authorized devices . The assay is composed of two principal steps: (1) extraction of RNA from patient specimens, (2) one-step multiplex reverse transcription and PCR amplification with human seasonal influenza A virus subtypes and the 2009 H1N1 influenza virus specific primers, and real-time detection with seasonal influenza A virus subtypes and the 2009 H1N1 influenza virus specific probes.

The Prodesse ProFlu-ST Assay kit includes:

  • ProFlu-ST Supermix that contains buffer, MgCl 2, nucleotides (dNTPs), Fast Start Taq polymerase, 4 pairs of oligonucleotide primers and 4 probes (4 sets)
  • M-MLV Reverse Transcriptase
  • RNase Inhibitor
  • Influenza A subtyping RNA Control (pooled RNA control for all three detections)
  • Internal Control

The Prodesse ProFlu-ST Assay includes the following primer and probe sets:

  •  Seasonal H1 detects a conserved area of the seasonal influenza A/H1 Hemagglutinin (HA) gene.
  •  Seasonal H3 detects a conserved area of the seasonal influenza A/H3 Hemagglutinin (HA) gene.
  •  2009 H1N1 Influenza (S-OIV) detects a conserved area of the 2009 H1N1 Influenza Nucleoprotein (NP) gene.
  •  Internal RNA Control III detects an 1158 base-long RNA transcript (MS2 Bacteriophage sequence) that is noncompetitive with the other targets of the ProFlu-ST Assay.

Control materials to be used with the Prodesse ProFlu-ST Assay include:

  •  Internal RNA Control III (IC) is a non-infectious in vitro transcribed 1158 base-long RNA (MS2 Bacteriophage sequence). The IC is incorporated into every sample and is carried through all steps of the procedure from nucleic acid isolation and purification through amplification to monitor for inhibitors present in the specimen or reaction tube. The IC also serves as a general process control ensuring that each step of the procedure is performed correctly, assay and instrument parameters are set correctly, and that general reagents are working.
  •  Influenza A Subtyping RNA Control (PC) is a pooled control containing three RNA transcripts, one each for the A/H1, A/H3, and A/2009 H1N1 detections targeted by the ProFlu-ST Assay. The PC does not go through nucleic acid isolation and purification, but is included during set-up of the RT-PCR reaction. The PC is required for each ProFlu-ST assay run. The PC in conjunction with the IC is used to verify reagent and system performance.
  •  Negative Control (NC) is blank viral transport medium used to monitor reagent and/or environmental contamination.
  •  Extraction Control (EC) is a previously characterized positive seasonal influenza A (H1 or H3) sample, positive 2009 H1N1 influenza sample, or a negative sample spiked with a well characterized seasonal influenza (H1 or H3) strain or 2009 H1N1 influenza strain. Good laboratory practice recommends including a positive extraction control in each nucleic acid isolation run. The extraction control should be treated like a sample during assay performance and analysis.

The Prodesse ProFlu-ST Assay requires the following instruments with corresponding software:

  • The ProFlu-ST Assay utilizes the Roche MagNA Pure LC System with software version 3.0.11 or the bioMérieux NucliSENS easyMAG System with software version 1.0.1 or 2.0 for nucleic acid extraction.
  • The ProFlu-ST Assay utilizes the Cepheid SmartCycler II system with Dx software versions 1.7b, 3.0a, or 3.0b for amplification and detection.

The above Prodesse ProFlu-ST Assay, when labeled consistently with the labeling agreed to by FDA and titled Prodesse ProFlu-ST Assay Instructions for Use, 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 Prodesse ProFlu-ST Assay is authorized to be accompanied by the following information pertaining to the emergency use, which is authorized to be made available to healthcare providers and patients:

  • Fact Sheet For Healthcare Providers: Interpreting the Prodesse ProFlu-ST Assay Results
  • Fact Sheet For Patients: Understanding the Prodesse ProFlu-ST Assay Results

As described in section IV below, Prodesse Inc. CLIA High Complexity Laboratories are also authorized to make available additional information relating to the emergency use of the authorized Prodesse ProFlu-ST Assay 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 Prodesse ProFlu-ST Assay in the specified population, when used for diagnosis of 2009 H1N1 influenza virus infection aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results, 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 Prodesse ProFlu-ST Assay may be effective in the diagnosis of 2009 H1N1 influenza virus infection aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results 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 Prodesse ProFlu-ST Assay, when used to diagnose 2009 H1N1 influenza virus infection aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results 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 Prodesse ProFlu-ST Assay 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 Prodesse ProFlu-ST Assay described above is authorized to diagnose 2009 H1N1 influenza virus infection aided by an algorithm that relies on seasonal influenza A/H1 virus and seasonal influenza A/H3 virus results in individuals who are diagnosed with influenza A by currently available FDA-cleared or authorized devices.

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 Prodesse ProFlu-ST Assay 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 Prodesse ProFlu-ST Assay.
  • 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:

Prodesse Inc.

  1. Prodesse, Inc. will distribute the Prodesse ProFlu-ST Assay with the labeling agreed to by FDA and titled Prodesse ProFlu-ST Assay Instructions for Use, as may be revised with written permission of FDA, only to CLIA High Complexity Laboratories.
  2. Prodesse, Inc. will provide to the CLIA High Complexity Laboratories the authorized Prodesse ProFlu-ST Assay Fact Sheet for Healthcare Providers and the authorized Prodesse ProFlu-ST Assay Fact Sheet for Patients.
  3. Prodesse, Inc. will make available on its website the authorized Prodesse ProFlu-ST Assay Fact Sheet for Healthcare Providers and the authorized Prodesse ProFlu-ST Assay Fact Sheet for Patients.
  4. Prodesse, Inc. will ensure that the state and/or local public health authority(ies) are informed of this EUA, including the terms and conditions herein.
  5. As a condition of this EUA, all advertising and promotional descriptive printed matter relating to the use of the Prodesse ProFlu-ST Assay shall be consistent with the Fact Sheets and labeling agreed to by FDA and titled Prodesse ProFlu-ST Assay Instructions for Use, as well as the terms set forth in this EUA and other requirements set forth in the Act and FDA regulations.
  6. As a condition of this EUA, all advertising and promotional descriptive printed matter relating to the use of the Prodesse ProFlu-ST Assay 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 has been authorized only for the diagnosis of 2009 H1N1 influenza virus infection in patients who have already been diagnosed with influenza A by currently available FDA-cleared or authorized devices;
    • 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.
  7. No advertising or promotional descriptive printed matter relating to the use of the Prodesse ProFlu-ST Assay may represent or suggest that this test is safe or effective for the diagnosis of 2009 H1N1 influenza virus, seasonal influenza A/H1 virus, or seasonal influenza A/H3 virus.
  8. Prodesse, Inc. will ensure CLIA High Complexity Laboratories have a process in place for reporting test results to healthcare providers and federal, state and/or local public health authorities, as appropriate.
  9. Prodesse, Inc. will track adverse events and report to FDA as required under 21 CFR part 803.
  10. Through a process of inventory control, Prodesse, Inc. will maintain records of device usage.
  11. Prodesse, Inc. 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 Prodesse, Inc becomes aware.

CLIA High Complexity Laboratories

  1. CLIA High Complexity Laboratories will test a patient sample using the Prodesse ProFlu - ST Assay only when the patient sample has already been tested positive for Influenza A by a currently available FDA-cleared nucleic acid amplification technologies (NAAT)- based Influenza A device with high performance5.
  2. CLIA High Complexity Laboratories will include with reports of the results of the Prodesse ProFlu-ST Assay the authorized fact sheets for health care providers and the authorized fact sheets for patients.
  3. CLIA High Complexity Laboratories will use the Roche MagNA Pure LC System or the bioMérieux NucliSENS easyMAG System for nucleic acid extraction, and perform the assay on the Cepheid SmartCycler II Real-time PCR instrument.
  4. CLIA High Complexity Laboratories will have a process in place for reporting test results to healthcare providers and federal, state and/or local public health authorities, as appropriate.
  5. CLIA High Complexity Laboratories will collect information on the performance of the assay, and report to Prodesse, Inc. any suspected occurrence of false positive or false negative results of which CLIA High Complexity Laboratories become aware.

Prodesse, Inc. and CLIA High Complexity Laboratories

  1. Prodesse, Inc. is authorized to make available additional information relating to the emergency use of the authorized Prodesse ProFlu-ST Assay that is consistent with, and does not exceed, the terms of this letter of authorization.
  2. Only Prodesse, Inc. may request changes to the authorized Prodesse ProFlu-AT Assay Fact Sheet for Healthcare Providers or the authorized Prodesse ProFlu-AT Assay Fact Sheet for Patients. Such requests will be made by contacting FDA concerning FDA review and approval.
  3. Prodesse, Inc. and CLIA High Complexity Laboratories 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 Prodesse ProFlu-ST Assay 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 Memorandum, Determination Pursuant to § 564 of the Federal Food, Drug, and Cosmetic Act (April 26, 2009).

2 FDA is authorizing the emergency use of the Prodesse ProFlu-ST Assay as described in the scope section of this letter (Section II).

3 Although there are no approved or cleared tests for the diagnosis of 2009 H1N1 influenza virus, to date, several devices have been FDA authorized under EUA to help address diagnostic needs. The information on the authorized devices is available at http://www.fda.gov/MedicalDevices/ Safety/EmergencySituations/ucm161496.htm.

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

5 An FDA-cleared NAAT-based Influenza A device with high performance is an FDA cleared NAAT-based IVD device detecting Influenza A that demonstrates sensitivity (compared to viral culture) of at least 95% and specificity of at least 92% with a lower bound of 95% (two-sided) confidence interval exceeding 90% and that does not require culture confirmation for negative results.