(1 days)
The Non-variola Orthopoxvirus Real-ime PCR Primer and Probe Set is intended for the 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 IIIness 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 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 virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Use is limited to Centers for Disease Control and Prevention designated laboratories.
Unchanged from original submission (K221658).
This document, a 510(k) summary for the "Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set" (K221834) from the Centers for Disease Control and Prevention (CDC), does not provide details on acceptance criteria or the specific study proving the device meets those criteria directly within the provided text.
Instead, it refers to a predicate device (K221658) and indicates that the current submission (K221834) is similar, with the main change being labeling. It explicitly states:
- "Unchanged from original submission (K221658)" for Device Description, Principle of Operation, Sample Types, and Instrumentation/Software.
- For "Analytical Limit of Detection (LoD)", "Analytical Sensitivity and Specificity", and "Clinical Performance," it repeatedly states: "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."
Therefore, based solely on the provided text, the specific information requested cannot be fully extracted. However, I can provide a template of what such an answer would look like if the information were available, and address what can be inferred or is explicitly absent.
Unable to fully answer based on provided text. The document refers to a predicate device and directs inquiries for performance characteristics to the CDC, rather than detailing them.
Here's an overview of the requested information based on what is and isn't present in the document:
1. Table of Acceptance Criteria and Reported Device Performance
This information is not provided in the document.
2. Sample Size Used for the Test Set and Data Provenance
This information is not provided in the document. The document refers to performance characteristics from a previous submission (K221658) and states inquiries should be directed to the CDC.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This information is not provided in the document. As this is an in vitro diagnostic (PCR test), ground truth would likely be established through a combination of culture, sequencing, or other highly sensitive and specific reference methods, rather than expert interpretation of images/clinical findings.
4. Adjudication Method
This information is not applicable/provided in the context of a PCR assay. Adjudication methods like 2+1 or 3+1 are typically used for subjective evaluations (e.g., image interpretation by radiologists or pathologists).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This information is not applicable/provided in the context of this device. An MRMC study is relevant for devices involving human interpretation (e.g., AI for radiology). This device is a molecular diagnostic assay.
6. Standalone Performance Study
Yes, this device is inherently a standalone algorithm/assay without human-in-the-loop performance measurement beyond the technician performing the PCR and interpreting the quantitative PCR cycles. The document implies such a performance study must have been conducted for the predicate device (K221658) when it mentions "Analytical Limit of Detection (LoD)," "Analytical Sensitivity and Specificity," and "Clinical Performance" studies, even though the results are not detailed here.
7. Type of Ground Truth Used
For a PCR assay, the ground truth for performance studies (LoD, analytical sensitivity, clinical performance) would typically be established by:
- Reference Methods: Culture, sequencing, or a validated gold-standard molecular test for the detection of non-variola Orthopoxviruses.
- Well-characterized samples: Use of known positive and negative controls, spiked samples, and clinical samples with confirmed infection status.
This specific detail is not provided in the document, but these are the standard ground truth types for such a device.
8. Sample Size for the Training Set
This information is not provided in the document. For PCR primer and probe design, a "training set" might refer to the genomic sequences used to design the primers and probes. For assay validation, there isn't a "training set" in the machine learning sense; rather, there are analytical and clinical validation samples.
9. How the Ground Truth for the Training Set was Established
This information is not provided in the document, and the concept of "ground truth for a training set" is less directly applicable in the same way as it is for machine learning models. For a PCR assay, primer and probe sequences are designed based on conserved regions of target genomes. Validation samples would then have their true status established by highly reliable reference methods.
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Centers For Disease Control And Prevention Julie Villanueva Laboratory Preparedness and Response Branch Chief 1600 Clifton Road, NE, MS: H24-11 Atlanta, Georgia 30329
June 24, 2022
Re: K221834
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: June 23, 2022 Received: June 23, 2022
Dear Julie Villanueva:
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
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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 https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Noel J. Gerald, Ph.D. Branch Chief Bacterial Respiratory and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K221834
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 intended for the 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 IIIness 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 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 virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Use is limited to Centers for Disease Control and Prevention designated laboratories.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | X |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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Centers for Disease Control and Prevention Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set Special 510(k)
510(k) Summary 15.
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Assigned 510(k)number: | TBD |
|---|---|
| Submitted by: | Centers for Disease Control and Prevention1600 Clifton Road NEAtlanta, GA 30329 |
| Contact Person: | Julie Villanueva, PhDLaboratory Preparedness and Response Branch ChiefDivision of Preparedness and Emerging InfectionsNational Center for Emerging and Zoonotic InfectiousDiseasesCenters for Disease Control and Prevention(Registration number: 1050190)1600 Clifton Road, NE, MS H24-11Atlanta, GA 30329(404) 639-3851 (office)Jfv3@cdc.gov |
| Date prepared: | June 23, 2022 |
| Device trade name: | Non-variola Orthopoxvirus Real-time PCRPrimer and Probe Set |
| Classification name andregulation (if applicable): | 21 CFR 866.3315 |
| Predicate device(s): | Non-variola Orthopoxvirus Real-time PCRPrimer and Probe Set (K221658) |
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
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Centers for Disease Control and Prevention Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set Special 510(k)
biothreat agents and emerging infectious diseases. Accordingly, scientists at 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 aqent 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 Orthopoxyiruses (e.q., Vaccinia, Cowpox, and Monkeypox 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.
As of June 21, 2022, LRN laboratories and the CDC have detected 141 (82 confirmed monkevpox virus. 59 confirmed orthopoxvirus) across 21 jurisdictions and 1 out of country resident. One additional case in Florida was diagnosed in the United Kingdom (U.K.) and is counted among U.K. cases. As case counts continue to rise in the United States and in 40 other countries where monkeypox is not endemic, there is an urgent need to prepare for larger scale diagnostic testing for orthopoxviruses. The use of the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set in CDC designated laboratories has introduced the need for product labeling that removes the LRN logo and LRN specific language. The following table outlines the similarities and differences between the two devices.
Device Description
Unchanged from original submission (K221658).
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 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
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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 Centers for Disease Control and Prevention 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(K221658) | |
|---|---|---|
| Device Name | Non-variola OrthopoxvirusReal-time PCR Primer andProbe Set | Non-variola OrthopoxvirusReal-time PCR Primer andProbe Set (K221658) |
| 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 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 orthopoxvirusesdetected by this assayand does not detectvariola virus. Refer to theCDC algorithm, Acute,Generalized Vesicular orPustular Rash IllnessTesting Protocol in the | 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 and ectromeliaviruses at varyingconcentrations. This assaydoes not differentiatevaccinia virus ormonkeypox virus fromother orthopoxvirusesdetected by this assay anddoes not detect variolavirus. Refer to the CDCalgorithm, Acute,Generalized Vesicular orPustular Rash IllnessTesting Protocol in the |
| United States forrecommended testing andevaluation algorithms forpatients presenting withacute, generalizedpustular or vesicular rashillness.Results of this assay arefor the identification ofnon-variola OrthopoxvirusDNA. These results mustbe used in conjunctionwith other diagnosticassays and clinicalobservations to diagnoseOrthopoxvirusinfection. The assayshould only be used totest specimens 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 treatmentor other patientmanagement decisions. | United States forrecommended testing andevaluation algorithms forpatients presenting withacute, generalized pustularor vesicular rash illness.Results of this assay arefor the identification ofnon-variola OrthopoxvirusDNA. These results mustbe used in conjunctionwith other diagnosticassays and clinicalobservations to diagnoseOrthopoxvirusinfection. The assayshould only 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 toCenters for DiseaseControl and Preventiondesignatedlaboratories. | 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 |
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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