(136 days)
The Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set is in vitro qualitative presumptive detection of non-variola Orthopoxvirus DNA extracted from human pustular rash specimens and viral cell culture lysates submitted to a Laboratory Response Network (LRN) reference laboratory. The assay detects non-variola Orthopoxvirus DNA, including Vaccinia, Cowpox, Monkeypox and Ectromelia viruses at varying concentrations. This assay does not differentiate Vaccinia virus or Monkeypox virus from other Orthopoxviruses detected by this assay and does not detect Variola virus. Refer to the CDC algorithm, Acute, Generalized Vesicular or Pustular Rash Illness Testing Protocol in the United States for recommended testing and evaluation algorithms for patients presenting with acute, generalized pustular or vesicular rash illness.
Results of this assay are for the presumptive identification of non-variola Orthopoxvirus DNA. These results must be used in conjunction with other diagnostic assays and clinical observations to diagnose Orthopoxvirus infection. The assay should only be used to test specimens with low/moderate risk of smallpox exists, viral culture should not be attempted. Negative results obtained with this device do not prection and should not be used as the sole basis for treatment or other patient management decisions.
Use is limited to Laboratory Response Network (LRN) designated laboratories.
With the exception of some reagents, the Non-variola Orthopoxvirus Realtime PCR Primer and Probe Set device description remains unchanged from the original submission (K053469).
The Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set Assay uses a fluorogenic probe, consisting of an oligonucleotide with a reporter dye (FAM) attached to the 5' end and a quencher dye (BHQ1) attached at or near the 3' end. The probe anneals to a specific target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5' nuclease activity of the Tag polymerase degrades the probe causing the reporter dye to separate from the quencher dye, thereby generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes and the fluorescence intensity is monitored during the PCR in real-time. The Taq polymerase used in this assay is inactive at room temperature and is activated by incubation at 95°C, thus minimizing the production of nonspecific amplification products.
Each extracted DNA sample is tested using the Non-variola Orthopoxvirus Real-time PCR Primer and Probe set alonq with an internal control primer and probe set(s) to demonstrate adequate DNA extraction and isolation, proper function of common reagents and equipment, and the absence of inhibitory substances.
I apologize, but the provided text from the FDA 510(k) clearance letter and summary for the "Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set" does not contain the detailed information necessary to answer your request about acceptance criteria and the study proving the device meets those criteria, especially in the context of an AI/human-in-the-loop system.
The document primarily focuses on the regulatory clearance of a PCR-based diagnostic kit, which is an in vitro diagnostic device. It's about detecting a specific DNA sequence, not interpreting medical images or assisting human readers in a diagnostic capacity.
Here's a breakdown of why the requested information cannot be extracted from this document, and what the document does discuss:
Why the document doesn't fit your request:
- Type of Device: This is a PCR primer and probe set, a molecular diagnostic tool. Your request is structured around AI-assisted image analysis or diagnostic systems that involve human readers and ground truth established by experts (e.g., radiologists interpreting images). The "device performance" here is about analytical sensitivity and specificity of a molecular test, not the performance of an AI algorithm in a clinical setting with human interaction.
- Study Design: The document refers to "Analytical Limit of Detection (LoD)" and "Analytical Sensitivity and Specificity" studies, and generally mentions "Clinical Performance" but directs inquiries to the CDC. It does not describe the specific methodologies of these studies in detail, particularly not in the context of a "test set" for an AI or human reader study.
- Absence of AI/Human-in-the-loop: There is no mention of an AI component, human readers, expert consensus for imaging interpretation, or MRMC studies.
What the document does provide (but isn't what you asked for):
- Device Name: Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set
- Intended Use: Qualitative presumptive detection of non-variola Orthopoxvirus DNA from human pustular rash specimens and viral cell culture lysates in Laboratory Response Network (LRN) reference laboratories. It specifically states it does not differentiate between certain Orthopoxviruses and does not detect Variola virus.
- Principle of Operation: Real-time PCR using a fluorogenic probe, demonstrating DNA extraction, reagent function, and absence of inhibitors.
- Predicate Device: Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (K053469)
- Sample Types: Vesicle fluid, skin, crust, "roof", dry/wet swab of lesion, touch prep, fresh biopsy, viral cell culture lysates.
Therefore, I cannot populate the table or answer the specific questions about acceptance criteria, test sets, expert ground truth, adjudication methods, MRMC studies, or standalone performance for an AI device using the provided text.
The document simply states that inquiries regarding performance characteristics should be directed to the Centers for Disease Control and Prevention, indicating that the detailed study results are not included in this summary.
{0}------------------------------------------------
September 20, 2018
Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services seal on the left and the FDA acronym along with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name written out to the right of it.
Centers for Disease Control and Prevention Yon Yu, Pharm.D. Associate Director for Regulatory Affairs 1600 Clifton Road NE, MS-C18 Atlanta, Georgia 30329
Re: K181205
Trade/Device Name: Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set Regulation Number: 21 CFR 866.3315 Regulation Name: Nucleic acid based reagents for detection of non-variola orthopoxviruses Regulatory Class: Class II Product Code: PBK Dated: May 4, 2018 Received: May 7, 2018
Dear Yon Yu, Pharm.D .:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination. product submissions. 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see
{1}------------------------------------------------
https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR 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 comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Uwe Scherf -S
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K181205
Device Name
Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set
Indications for Use (Describe)
The Non-variola Orthopoxvirus Real-ime PCR Primer and Probe Set is in vitro qualitative presumptive detection of non-variola Orthopoxvirus DNA extracted from human pustular rash specimens and viral cell culture lysates submitted to a Laboratory Response Network (LRN) reference laboratory. The assay detects non-variola Orthopoxvirus DNA, including Vaccinia, Cowpox, Monkeypox and Ectromelia viruses at varying concentrations. This assay does not differentiate Vaccinia virus or Monkeypox virus from other Orthopoxviruses detected by this assay and does not detect Variola virus. Refer to the CDC algorithm, Acute, Generalized Vesicular or Pustular Rash Illness Testing Protocol in the United States for recommended testing and evaluation algorithms for patients presenting with acute, generalized pustular or vesicular rash illness.
Results of this assay are for the presumptive identification of non-variola Orthopoxvirus DNA. These results must be used in conjunction with other diagnostic assays and clinical observations to diagnose Orthopoxvirus infection. The assay should only be used to test specimens with low/moderate risk of smallpox exists, viral culture should not be attempted. Negative results obtained with this device do not prection and should not be used as the sole basis for treatment or other patient management decisions.
Use is limited to Laboratory Response Network (LRN) designated laboratories.
| 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) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
Centers for Disease Control and Prevention Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set 510(k) Premarket Notification
510(k) Summary 5.
This summary of 510(k) information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Assigned 510(k)number: | |
|---|---|
| Submitted by: | Centers for Disease Control and Prevention1600 Clifton Road NEAtlanta, GA 30329 |
| Contact Person: | CDR Yon Yu, Pharm.D.Associate Director for Regulatory AffairsOffice of the DirectorNational Center for Emerging and Zoonotic Infectious DiseasesCenters for Disease Control and Prevention(Registration number: 1050190)1600 Clifton Road, NE, MS C-18Atlanta, GA 30329(404) 639-3046 (office)(404) 639-1275 (fax)fkb8@cdc.gov |
| Date prepared: | May 4, 2018 |
| Device trade name: | Non-variola Orthopoxvirus Real-time PCRPrimer and Probe Set |
| Classification name andregulation: (if applicable) | 21 CFR 866.3316 |
| Predicate device(s): | Non-variola Orthopoxvirus Real-time PCRPrimer and Probe Set (K053469) |
Background
Variola virus, a member of the Orthopoxvirus genus, is the causative agent of smallpox and was certified eradicated in 1980 by the World Health Organization. At that time, smallpox vaccinations were ceased worldwide as a result. However, in recent years, concerns over the potential use of Variola virus as a biological weapon led the United States to resume smallpox vaccinations on a limited basis. Since the smallpox vaccine contains live Vaccinia virus, it is possible for vaccine recipients and/or their close contacts to develop adverse reactions to the vaccine including the emergence of pustules on the skin.
The Laboratory Response Network (LRN) is part of a national bioterrorism preparedness initiative created to ensure an effective laboratory response to biological threats by helping to improve the nation's public health laboratory infrastructure. Member laboratories must meet specific membership requirements and pass rigorous proficiency tests demonstrating their ability to accurately identify agents of concern. One of the major goals is the development and validation of rapid and specific assays for detection of biothreat agents and emerging infectious diseases. Accordingly, scientists at
{4}------------------------------------------------
the Centers for Disease Control and Prevention have developed several realtime PCR based assays to detect non-variola Orthopoxvirus and other potential biothreat agents in an effort to meet the need for rapid detection.
The Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set was developed for use in conjunction with clinical observations and other tests as described in the CDC algorithm, Acute, Generalized Vesicular or Pustular Rash Illness Testing Protocol in the United States. The assay is designed to aid in the identification of the causative agent of a pustular or vesicular rash illness and to help rule out the presence of Variola virus in patients presenting with pustular rash illness.
This assay detects most commonly known human pathogenic Orthopoxviruses (e.g. Vaccinia. Cowpox, and Monkevpox viruses) but does not detect Variola virus, the causative agent of smallpox. Vaccinia virus infection in the United States usually occurs in conjunction with smallpox vaccination or contact with a smallpox vaccine recipient. Monkeypox and Cowpox viruses are endemic to locations outside the United States, with the exception of the 2003 monkeypox outbreak associated with prairie dogs, which became infected due to imported African rodents.
Device Description
With the exception of some reagents, the Non-variola Orthopoxvirus Realtime PCR Primer and Probe Set device description remains unchanged from the original submission (K053469).
The Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set Assay uses a fluorogenic probe, consisting of an oligonucleotide with a reporter dye (FAM) attached to the 5' end and a quencher dye (BHQ1) attached at or near the 3' end. The probe anneals to a specific target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5' nuclease activity of the Tag polymerase degrades the probe causing the reporter dye to separate from the quencher dye, thereby generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes and the fluorescence intensity is monitored during the PCR in real-time. The Taq polymerase used in this assay is inactive at room temperature and is activated by incubation at 95°C, thus minimizing the production of nonspecific amplification products.
Each extracted DNA sample is tested using the Non-variola Orthopoxvirus Real-time PCR Primer and Probe set alonq with an internal control primer and probe set(s) to demonstrate adequate DNA extraction and isolation, proper function of common reagents and equipment, and the absence of inhibitory substances.
Intended Use
The Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set is intended for the in vitro qualitative presumptive detection of non-variola Orthopoxvirus DNA extracted from human pustular or vesicular rash specimens and viral cell culture lysates submitted to a Laboratory Response Network (LRN) reference laboratory. The assay detects non-variola Orthopoxvirus DNA, including Vaccinia, Cowpox, Monkeypox and Ectromelia
{5}------------------------------------------------
viruses at varying concentrations. This assay does not differentiate Vaccinia virus or Monkeypox virus from other Orthopoxviruses detected by this assay and does not detect Variola virus. Refer to the CDC algorithm, Acute, Generalized Vesicular or Pustular Rash Illness Testing Protocol in the United States for recommended testing and evaluation algorithms for patients presenting with acute, generalized pustular or vesicular rash illness.
Results of this assay are for the presumptive identification of non-variola Orthopoxvirus DNA. These results must be used in conjunction with other diagnostic assays and clinical observations to diagnose Orthopoxvirus infection. The assay should only be used to test specimens with low/moderate risk of smallpox. If a high risk of smallpox exists, viral culture should not be attempted. Negative results obtained with this device do not preclude Variola virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Use is limited to Laboratory Response Network (LRN) designated laboratories.
Device Comparison
The following table summarizes the similarities and differences between the cleared assay and the new submission for this device.
| New Submission | Original Submission | |
|---|---|---|
| Device | Non-variola OrthopoxvirusReal-time PCR Primer andProbe Set | Non-variola OrthopoxvirusReal-time PCR Primer andProbe Set (K053469) |
| Intended Use | The Non-variolaOrthopoxvirus Real-timePCR Primer and Probe Setis intended for the in vitroqualitative presumptivedetection of non-variolaOrthopoxvirus DNAextracted from humanpustular or vesicular rashspecimens and viral cellculture lysates submitted toa Laboratory ResponseNetwork (LRN) referencelaboratory. The assaydetects non-variolaOrthopoxvirus DNA,including Vaccinia, Cowpox,Monkeypox and Ectromeliaviruses at varyingconcentrations. This assaydoes not differentiateVaccinia virus orMonkeypox virus from otherOrthopoxviruses detected | The Non-variolaOrthopoxvirus Real-timePCR Primer and Probe Setis intended for the in vitroqualitative presumptivedetection of non-variolaOrthopoxvirus DNAextracted from humanpustular or vesicular rashspecimens and viral cellculture lysates submittedto a Laboratory ResponseNetwork (LRN) referencelaboratory. The assaydetects non-variolaOrthopoxvirus DNA,including vaccinia,cowpox, monkeypox andectromelia viruses atvarying concentrations.This assay does notdifferentiate vaccinia virusor monkeypox virus fromother orthopoxviruses |
| by this assay and does notdetect Variola virus. Referto the CDC algorithm,Acute, GeneralizedVesicular or Pustular RashIllness Testing Protocol inthe United States forrecommended testing andevaluation algorithms forpatients presenting withacute, generalized pustularor vesicular rash illness.Results of this assay are forthe presumptiveidentification of non-variolaOrthopoxvirus DNA. Theseresults must be used inconjunction with otherdiagnostic assays andclinical observations todiagnose Orthopoxvirusinfection. The assay shouldonly be used to testspecimens withlow/moderate risk ofsmallpox. If a high risk ofsmallpox exists, viralculture should not beattempted. Negativeresults obtained with thisdevice do not precludeVariola virus infection andshould not be used as thesole basis for treatment orother patient managementdecisions.Use is limited toLaboratory ResponseNetwork (LRN)designatedlaboratories. | detected by this assayand does not detectvariola virus. Refer to theCDC algorithm, Acute,Generalized Vesicular orPustular Rash IllnessTesting Protocol in theUnited States forrecommended testing andevaluation algorithms forpatients presenting withacute, generalizedpustular or vesicular rashillness.This assay should be usedin conjunction with otherdiagnostic assays andclinical observations forthe following indications:(1) to serve as an aid indetermining whetherVaccinia virus is thecausative agent of avaccination adverse | |
| NOTE: If a high risk ofsmallpox exists, viralculture should not beattempted. | ||
| Use is limited toLaboratory ResponseNetwork (LRN)designatedlaboratories. | ||
| Principle ofOperation | Unchanged | Nucleic acid amplificationand fluorescent probedetection |
| Sample Types | Unchanged | • Vesicle fluid, skin,crust, "roof"• Dry or wet swab oflesion (dry swab ispreferred)• Touch prep (slide) oflesion• Fresh biopsy of pustuleor vesicle (no formalin)• Viral cell culture lysates |
| Instrumentationand Software | Unchanged | Real-time PCRinstrumentation andsoftware |
{6}------------------------------------------------
{7}------------------------------------------------
Establishment of Performance Characteristics
Inquiries regarding performance characteristics for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set should be directed to the Centers for Disease Control and Prevention.
Analytical Limit of Detection (LoD)
The limit of detection for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set was determined through an analytical sensitivity study.
Analytical Sensitivity and Specificity
Inquiries regarding performance characteristics for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set should be directed to the Centers for Disease Control and Prevention.
Clinical Performance
Inquiries regarding clinical performance characteristics for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set should be directed to the Centers for Disease Control and Prevention.
N/A