(651 days)
Not Found
No
The device is a chemical preservative fluid and does not involve any computational analysis or algorithms.
No.
This device is intended to stabilize and inactivate infectious samples for diagnostic testing, not to treat or prevent disease in a patient.
No
The Sample Preservative Fluid is intended for the stabilization and inactivation of specimens, making them suitable for use with compatible molecular diagnostic devices, rather than being a diagnostic device itself.
No
The device is a Sample Preservative Fluid, which is a liquid medium for stabilizing biological specimens. It is a physical substance and not software.
Based on the provided information, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the Sample Preservative Fluid is for the "stabilization, and inactivation of infectious, unprocessed, upper respiratory specimens suspected of containing Influenza A virus." It also states that specimens transported in this fluid are "suitable for use with compatible legally marketed molecular diagnostic devices." This clearly indicates its role in the pre-analytical phase of a diagnostic test.
- Device Description: The description details the composition of the fluid and its purpose in "stabilization of Influenza A RNA during sample transport/storage." This function is directly related to preparing a sample for in vitro diagnostic testing.
- Performance Studies: The performance studies described (Detection Limit, Specimen stability, Viral Inactivation Study) are all focused on evaluating the device's ability to preserve and inactivate the target analyte (Influenza A RNA) for subsequent diagnostic testing. The use of a legally marketed molecular diagnostic device (Cepheid Xpert Xpress Flu/RSV Assay) in these studies further reinforces its role as an IVD component.
- Predicate Device: The mention of a predicate device (PrimeStore MTM, DEN170029) which is also a sample collection and transport medium for molecular diagnostics, strongly suggests that this device falls under the same regulatory category as an IVD.
While the device itself doesn't perform the diagnostic test, its function in stabilizing and preparing the sample for a legally marketed molecular diagnostic device makes it an integral part of the in vitro diagnostic process.
N/A
Intended Use / Indications for Use
The Sample Preservative Fluid is intended for the stabilization, transportation, and inactivation of infectious, unprocessed, upper respiratory specimens suspected of containing Influenza A virus. Specimens transported in the Sample Preservative Fluid are stable refrigerated (2-8°C) and at room temperature (20-25°C). The Sample Preservative Fluid is suitable for use with compatible legally marketed molecular diagnostic devices.
Product codes
QBD
Device Description
Sample Preservative Fluid is a medium for stabilization of Influenza A RNA during sample transport/storage. The fluid is composed of quanidine thiocyanate, Triton X-100, and nuclease-free water. Sample Preservative Fluid is provided in a labeled screw-cap tube.
Sample Preservative Fluid configuration:
- BSC82X1-A1: a screw-cap tube filled with 2 mL of Sample Preservative Fluid liquid ● and a prepackaged nasopharyngeal swab for sample collection
- Nasopharyngeal swab: regular size, sterile disposable sample swab (80mm . breakpoint)
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
upper respiratory specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Non-clinical Testing
7.1 Shelf-life:
Study type: Shelf-life assessment.
Sample size: Three lots of Sample Preservative Fluid.
Key results: All three lots stored at 2-8°C and 25°C met physical and chemical property evaluation acceptance criteria for all timepoints. There was no bacterial or fungal growth, change in appearance, no leakage, and no change in density over time. The shelf-life of the reagent when stored at 2-25°C is 24 months.
7.2 Detection Limit:
Study type: Limit of Detection (LoD) testing.
Sample size: For preliminary LoD, 5 replicates per dilution. For confirmatory LoD, 20 replicates at 0.04 TCID50/mL and 100% of replicates at 0.08 TCID50/mL were positive.
Key results: Confirmatory LoD for Influenza A H3N2 (A/California/2/2014, VR-1938) was 0.08 TCID50/mL.
7.3 Specimen stability:
Study type: Specimen stability study.
Sample size: Each of three reagent lots tested in replicates of four.
Key results: The Influenza A H3N2 virus nucleic acid was preserved in the Sample Preservative Fluid without degradation at refrigeration (2-4°C) and room (20-25°C) temperatures for 35 days. All the Ct values fell within a 3.0 Ct range of results from the Ct values generated for time point zero.
- Viral Inactivation Study:
Study type: Inactivation study and Cytotoxicity Study.
Key results - Cytotoxicity: No toxicity was observed to the MDCK cell monolayer when the Sample Preservative Fluid was diluted to equal to or greater than 3500 times.
Key results - Inactivation: The result was ≥4.7 logarithmic reduction in Influenza A after 30 and 60 seconds in the Sample Preservative Fluid. The device demonstrated viral inactivation of >99.99%.
Key Metrics
- Shelf-life: 24 months
- LoD: 0.08 TCID50/mL for Influenza A H3N2
- Specimen stability: 35 days at 2-25°C
- Viral Inactivation: ≥4.7 logarithmic reduction in Influenza A (>99.99% inactivation)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.2950 Microbial nucleic acid storage and stabilization device.
(a)
Identification. A microbial nucleic acid storage and stabilization device is a device that consists of a container and reagents intended to stabilize microbial nucleic acids in human specimens for subsequent isolation and purification of nucleic acids for further molecular testing. The device is not intended for preserving morphology or viability of microorganisms.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of microorganisms and types of human specimens intended to be preserved.
(2) The labeling required under § 809.10(b) of this chapter must include the following:
(i) A detailed device description, including all device components;
(ii) Performance characteristics from applicable analytical studies, including nucleic acid stability and microorganism inactivation;
(iii) A limiting statement that erroneous results may occur when the transport device is not compatible with molecular testing; and
(iv) A limiting statement that the device has only been validated to preserve the representative microorganisms used in the analytical studies.
(3) Design verification and validation must include the following:
(i) Overall device design, including all device components and all control elements incorporated into the analytical validation procedures;
(ii) Thorough description of the microorganisms and methodology used in the validation of the device including, extraction platforms and assays used for the detection of preserved nucleic acids; and
(iii) The limit of detection (LoD) of the molecular test used to establish microorganism nucleic acid stability.
0
June 26, 2024
Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
Hangzhou Bioer Technology Co., Ltd % Hanson Chen Official Correspondent Shenzhen Joyantech Consulting Co., Ltd 1713A, 17th Floor, Block A. Zhongguan Times Square, Nanshan District Shenzhen, Guangdong GD755, China
Re: K222771
Trade/Device Name: Sample Preservative Fluid Regulation Number: 21 CFR 866.2950 Regulation Name: Microbial Nucleic Acid Storage And Stabilization Device Regulatory Class: Class II Product Code: QBD Dated: July 25, 2022 Received: September 14, 2022
Dear Hanson Chen:
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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
1
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820,181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 medical devices and radiation-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 -S
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
2
Indications for Use
510(k) Number (if known) K222771
Device Name Sample Preservative Fluid
Indications for Use (Describe)
The Sample Preservative Fluid is intended for the stabilization, and inactivation of infectious, unprocessed, upper respiratory specimens suspected of containing Influenza A virus. Specimens transported in the Sample Preservative Fluid are stable refrigerated (2-8°C) and at room temperature (20-25°C). The Sample Preservative Fluid is suitable for use with compatible legally marketed molecular diagnostic devices.
| 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) |
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C)
3
.
Product: Sample Preservative Fluid
510(k) Summary
1. Submission Sponsor
| Applicant Name | HANGZHOU BIOER TECHNOLOGY CO.,LTD |
|---|---|
| Address | 1192 BinAn Rd, Binjiang District, Hangzhou, PEOPLE'S |
| REPUBLIC OF CHINA | |
| Phone No. | +86-571-87774567 |
| Contact person | Zoey Zhang |
| RA Department | |
| Contact person's | |
| zhangyu@bioer.com.cn | |
| Date Prepared | June 24, 2024 |
Consultant information
| Name | Shenzhen Joyantech Consulting Co., Ltd |
|---|---|
| Address | 1713A, 17th Floor, Block A, Zhongguan Times Square, |
| Nanshan District, Shenzhen | |
| Image: [logo] | |
| 卓远天成 | |
| Post Code | 518000 |
| Phone No. | +86-755-86069197 |
| Contact person | Hanson Chen |
| Contact person's | |
| hanson@cefda.com |
2. Device information
| Trade name | Sample Preservative Fluid |
|---|---|
| Common name | Sample Preservative Fluid |
| Model | BSC82X1-A1 |
| Classification | II |
| Classification name | Microbial Nucleic Acid Storage And Stabilization Device |
| Product code | QBD |
| Regulation No. | 21 CFR 866.2950 |
3. Legally Marketed Predicate Device
| Trade Name | PrimeStore MTM |
|---|---|
| 510(k) Number | DEN170029 |
| Product Code | QBD |
| Manufacturer | Longhorn Vaccines and Diagnostics, LLC |
4
4. Device Description:
Sample Preservative Fluid is a medium for stabilization of Influenza A RNA during sample transport/storage. The fluid is composed of quanidine thiocyanate, Triton X-100, and nuclease-free water. Sample Preservative Fluid is provided in a labeled screw-cap tube.
Sample Preservative Fluid configuration:
- BSC82X1-A1: a screw-cap tube filled with 2 mL of Sample Preservative Fluid liquid ● and a prepackaged nasopharyngeal swab for sample collection
- Nasopharyngeal swab: regular size, sterile disposable sample swab (80mm . breakpoint)
5. Intended Use/Indication for Use:
The Sample Preservative Fluid is intended for the stabilization, transportation, and inactivation of infectious, unprocessed, upper respiratory specimens suspected of containing Influenza A virus. Specimens transported in the Sample Preservative Fluid are stable refrigerated (2-8°C) and at room temperature (20-25°C). The Sample Preservative Fluid is suitable for use with compatible legally marketed molecular diagnostic devices.
6. Substantial Equivalence Comparison:
| Device: K222771 | Predicate: DEN170029 | |
|---|---|---|
| Device Trade Name | Sample Preservative Fluid | PrimeStore MTM |
| General Device Characteristic Similarities | ||
| Intended Use / | ||
| Indications For Use | The Sample Preservative Fluid | |
| is intended for the stabilization, | ||
| transportation, and inactivation | ||
| of infectious, unprocessed, | ||
| upper respiratory specimens | ||
| suspected of containing | ||
| Influenza A virus. Specimens | ||
| transported in the Sample | ||
| Preservative Fluid are stable | ||
| refrigerated (2-8°C) and at | ||
| room temperature (20-25°C). | ||
| The Sample Preservative Fluid | ||
| is suitable for use with | ||
| compatible legally marketed | ||
| molecular diagnostic devices. | PrimeStore MTM is intended | |
| for the stabilization, | ||
| transportation and inactivation | ||
| of infectious unprocessed | ||
| nasal washes suspected of | ||
| containing Influenza A virus | ||
| RNA. PrimeStore MTM is also | ||
| intended for the stabilization, | ||
| transportation and inactivation | ||
| of infectious unprocessed | ||
| sputum samples suspected of | ||
| containing Mycobacterium | ||
| tuberculosis DNA from human | ||
| samples. | ||
| Specimen storage | ||
| temperature | 2-25 °C | 2-25 °C |
| Shelf-life | 24 months | 24 months |
| General Device Characteristic Differences | ||
| Microorganism | ||
| nucleic acids | ||
| preserved | Influenza A virus | Influenza A virus and |
| Mycobacterium tuberculosis | ||
| Specimen type | Upper respiratory specimens | Nasal washes and sputum |
| samples | ||
| Analyte | RNA | DNA, RNA |
| Specimen stability | 2-25 °C ≤ 35 days | For Influenza A virus: |
| 4 °C ≤ 29 days | ||
| 27 °C ≤ 8 days |
Non-clinical Testing 7.
7.1 Shelf-life:
5
Version: A/0
Three lots of Sample Preservative Fluid stored at 2-8°C and 25°C were assessed at 10 timepoints (0, 3, 6, 12, 13, 15, 18, 21, and 24 months). At each timepoint, each kit was evaluated for bacterial or fungal growth, changes in appearance, the tightness of the cap to ensure no leakage, and density of the liquid.
Acceptance criteria: There should be no bacterial or fungal growth, no obvious change in appearance, no tube leakage at -0.08 MPa for ten minutes, and a media density of 1.06 ± 0.04 g/mL.
All three lots stored at 2-8°C and 25°C met physical and chemical property evaluation acceptance criteria for all timepoints. There was no bacterial or fungal growth, change in appearance, no leakage, and no change in density over time. The shelf-life of the reagent when stored at 2-25°C is 24 months.
The Sample Preservative Fluid is not claimed to be sterile nor is it intended to be sterilized by the end user. These vials are single-use devices. The products are packaged in sterile PE bags to ensure the media is not contaminated during shipping.
7.2 Detection Limit:
Limit of detection (LoD) testing was conducted to evaluate the lowest concentration of analyte that can be detected at greater than or equal to 95% detection rate.
Preliminary Limit of Detection (LoD):
The cleared assay used to determine the LoD was the Cepheid Xpert Xpress Flu/RSV Assay (K180218) when testing samples collected in the subject device. The LoD of the Xpert Xpress Flu/RSV Assay for Influenza A H3N2 is:
- Influenza A/Perth/16/2009: 0.01 TCID50/mL .
- Influenza A/Victoria/361/2011: 0.75 TCID50/mL .
Because the two viral strains used in the Cepheid LoD study were no longer available, another Influenza A H3N2 strain, A/California/2/2014 VR-1938, was used.
Influenza A H3N2 (A/California/2/2014, VR-1938) was diluted with negative nasal matrix to 0.32 TCIDso/mL. Serial two-fold dilutions were performed to create samples at 0.16, 0.08, 0.04, 0.02 and 0.01 TCIDso/mL. Five replicates of each sample were tested for Influenza A with the Xpert Express Flu/RSV Assay, table 1 below. The lowest concentration that yielded a greater than or equal to 80% detection rate was further tested to confirm LoD.
| Influenza A
Concentration
(TCID50/mL) | Rep 1
(Ct) | Rep 2
(Ct) | Rep 3
(Ct) | Rep 4
(Ct) | Rep 5
(Ct) | Avg
(Ct) | SD
(Ct) | CV
(%) | Detection
Rate (%) |
|---------------------------------------------|---------------|---------------|---------------|---------------|---------------|-------------|------------|-----------|-----------------------|
| 0.32 | 33.4 | 33.1 | 34.2 | 33.2 | 33.4 | 33.5 | 0.39 | 1.16% | 100% |
| 0.16 | 34.3 | 34.5 | 36.9 | 34.2 | 34.3 | 34.8 | 1.03 | 2.97% | 100% |
| 0.08 | 35.0 | 36.1 | 35.3 | 35.2 | 34.5 | 35.2 | 0.51 | 1.47% | 100% |
| 0.04 | 37.3 | 36.2 | 39.2 | 36.8 | No Ct | 37.4 | 1.12 | 3.01% | 80% |
| 0.02 | 38.5 | 38.7 | 38.3 | No Ct | No Ct | 38.5 | 0.163 | 0.424% | 60% |
Table 1. Preliminary LoD test results:
6
HANGZHOU BIOER TECHNOLOGY CO.,LTD
510(k) Summary
Product: Sample Preservative Fluid
Version: A/0
| 0.01 | 37.9 | 37.3 | No Ct | No Ct | No Ct | 37.6 | 0.30
0 | 0.798
% | 40% |
| ------ | ------ | ------ | ------- | ------- | ------- | ------ | ----------- | ------------ | ----- |
|---|
Confirmatory Limit of Detection (LoD):
To confirm LoD, additional testing of 20 replicates at 0.04 TCIDso/mL was performed. When testing of 8 replicates at 0.04 TCIDso/mL yielded >2 negative results, testing was terminated and a retest was performed at 0.08 TCID50/mL. 100% of replicates at 0.08 TCIDso/mL were positive confirming the assay LoD as 0.08 TCIDso/mL, table 2 below.
Table 2. Confirmatory LoD test results:
| | 0.08 TCID50/mL
Influenza A (Ct) |
|--------------------|------------------------------------|
| Replicate | |
| 1 | 34.5 |
| 2 | 35.2 |
| 3 | 36.2 |
| 4 | 35.2 |
| 5 | 35.0 |
| 6 | 35.1 |
| 7 | 36.5 |
| 8 | 35.4 |
| 9 | 35.6 |
| 10 | 35.1 |
| 11 | 35.2 |
| 12 | 35.8 |
| 13 | 34.8 |
| 14 | 35.2 |
| 15 | 35.3 |
| 16 | 36.4 |
| 17 | 35.1 |
| 18 | 35.2 |
| 19 | 35.6 |
| 20 | 34.7 |
| Average | 35.4 |
| SD | 0.517 |
| CV (%) | 1.46% |
| Detection Rate (%) | 100% |
7.3 Specimen stability:
A specimen stability study was conducted to evaluate the stability of Influenza A virus RNA spiked into negative matrix and stored in Sample Preservative Fluid at a refrigerated temperature (2-4°C) and room temperature (20-25°C) for 35 days. Influenza A H3N2 (A/California/2/2014, VR-1938) was diluted to 3x the LoD (0.24 TCID50/mL) with negative nasal matrix collected with three reagent lots. Samples collected with each of the three lots were tested in replicates of four with the Xpert Xpress Flu/RSV Assay on Day 0. Samples were stored at refrigerated (2-4°C, table 3 below) and room temperature (20-25°C, table 4 below). Samples were tested in replicates of four on Days 1, 8, 15, 22, and 35.
Table 3. Influenza A stabilitv 2-4°C:
| Specimen | Lot | Rep | Day0 (Ct) | Day1 (Ct) | Day8 (Ct) | Day15 (Ct) | Day22 (Ct) | Day35 (Ct) |
|---|---|---|---|---|---|---|---|---|
| ---------- | ----- | ----- | ----------- | ----------- | ----------- | ------------ | ------------ | ------------ |
7
HANGZHOU BIOER TECHNOLOGY CO.,LTD
Product: Sample Preservative Fluid
510(k) Summary
Version: A/0
| 1 | 33.5 | 33.1 | 33.4 | 33.9 | 33.6 | 35.6 | ||
|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 33.5 | 34.0 | 33.7 | 34.0 | 33.9 | 34.3 | |
| 3 | 33.0 | 33.4 | 33.4 | 33.5 | 34.3 | 33.9 | ||
| 4 | 33.4 | 34.8 | 33.9 | 33.3 | 33.9 | 34.0 | ||
| 2 | 1 | 33.4 | 33.2 | 33.5 | 33.8 | 33.5 | ||
| 0.24 TCID50/mL | ||||||||
| Influenza A in | ||||||||
| nasal matrix | 2 | 34.0 | 33.4 | 33.4 | 33.9 | 34.0 | 34.4 | |
| 3 | 33.5 | 33.5 | 33.9 | 33.7 | 33.5 | 34.1 | ||
| 4 | 33.9 | 33.3 | 33.8 | 33.5 | 34.0 | 33.7 | ||
| 3 | 1 | 33.7 | 33.6 | 33.8 | 33.5 | 33.8 | ||
| 2 | 33.7 | 33.3 | 33.7 | 33.6 | 33.8 | 33.7 | ||
| 3 | 33.5 | 33.2 | 34.0 | 33.6 | 33.7 | 34.2 | ||
| 4 | 33.3 | 33.5 | 33.7 | 33.7 | 33.7 | 34.4 | ||
| Average | 33.5 | 33.5 | 33.7 | 33.7 | 33.8 | 34.2 | ||
| SD | 0.256 | 0.446 | 0.203 | 0.197 | 0.222 | 0.473 | ||
| CV | 0.764% | 1.33% | 0.604% | 0.586% | 0.655% | 1.38% |
Table 4. Influenza A stability 20-25°C:
| Specimen | Lot | Rep | Day0
(Ct) | Day1
(Ct) | Day8
(Ct) | Day15
(Ct) | Day22
(Ct) | Day35
(Ct) | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
|--------------------------------------------------|-----|------|--------------|--------------|--------------|---------------|---------------|---------------|--|---|------|------|------|------|------|------|--|---|------|------|------|------|------|------|---------|--|--|------|------|------|------|------|------|----|--|--|-------|-------|-------|-------|-------|-------|----|--|--|--------|--------|-------|--------|--------|
| 0.24 TCID50/mL
Influenza A in
nasal matrix | 1 | 1 | 34.0 | 34.1 | 34.3 | 33.6 | 33.4 | 33.9 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | | 2 | 34.0 | 33.9 | 33.3 | 33.9 | 33.9 | 34.7 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | | 3 | 33.7 | 33.3 | 34.0 | 33.9 | 33.9 | 34.1 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | | 4 | 33.5 | 33.9 | 34.3 | 34.2 | 33.7 | 34.4 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | 2 | 1 | 33.8 | 33.3 | 33.6 | 33.5 | 33.6 | 34.0 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | | 2 | 33.9 | 33.2 | 33.4 | 34.0 | 34.0 | 33.4 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | | 3 | 33.4 | 33.4 | 34.5 | 33.4 | 33.9 | 33.7 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | | 4 | 33.7 | 33.5 | 33.4 | 33.6 | 33.4 | 34.1 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | 3 | 1 | 34.0 | 33.4 | 33.6 | 33.3 | 33.7 | 34.1 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | | 2 | 33.5 | 33.0 | 33.7 | 34.3 | 34.0 | 35.2 | | 3 | 34.0 | 33.5 | 33.8 | 34.2 | 33.6 | 34.2 | | 4 | 34.3 | 33.1 | 33.6 | 34.1 | 33.7 | 34.0 | Average | | | 33.8 | 33.5 | 33.8 | 33.8 | 33.7 | 34.2 | SD | | | 0.254 | 0.325 | 0.379 | 0.180 | 0.201 | 0.443 | CV | | | 0.752% | 0.971% | 1.12% | 0.534% | 0.597% |
| | | 2 | 33.5 | 33.0 | 33.7 | 34.3 | 34.0 | 35.2 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | | 3 | 34.0 | 33.5 | 33.8 | 34.2 | 33.6 | 34.2 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| | 4 | 34.3 | 33.1 | 33.6 | 34.1 | 33.7 | 34.0 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| Average | | | 33.8 | 33.5 | 33.8 | 33.8 | 33.7 | 34.2 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| SD | | | 0.254 | 0.325 | 0.379 | 0.180 | 0.201 | 0.443 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
| CV | | | 0.752% | 0.971% | 1.12% | 0.534% | 0.597% | 1.30% | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
At each timepoint, Influenza A spiked into nasal matrix and preserved at refrigerated temperature (2-4°C) or room temperature (20-25°C) yielded positive results, which showed the Influenza A H3N2 nucleic acid was detected.
All the Ct values fell within a 3.0 Ct range of results from the Ct values generated for time point zero, which met the pre-defined acceptance criteria. The Influenza A H3N2 virus nucleic acid was preserved in the Sample Preservative Fluid without degradation at refrigeration (2-4°C) and room (20-25°C) temperatures for 35 days.
- Viral Inactivation Study: An inactivation study was performed to determine the rate the Sample Preservative Fluid
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inactivates Influenza A.
Cytotoxicity Study:
A cytotoxicity study was performed to determine at what dilution ratio the Sample Preservative Fluid would not be toxic to a cell monolayer.
A preliminary test was performed by diluting the Sample Preservative Fluid with complete cell culture medium at multiple dilutions (from 1:10 up to 1:8000) and adding it to a monolayer of cells. When the Sample Preservative Fluid dilution ratio exceeded 1:4000 both the test group and the control group showed normal cell morphology and growth, demonstrating that there was no significant cytotoxicity for the Sample Preservative Fluid with high dilution ratios.
A confirmatory test was performed by diluting the Sample Preservative Fluid with complete cell culture medium at multiple dilution (from 1:1000) and adding it to a monolayer of cells. When the dilution ratio reached or exceeded 1:3500, both the test group and the control group showed normal cell morphology and growth status, and no significant difference between the test group and the control group were observed.
When the dilution ratio reached or exceeded 1:3500, both the test group and the control group showed normal cell morphology and growth status, and no significant difference between the test group and the control group were observed. There was no toxicity to the MDCK cell monolayer when the Sample Preservative Fluid was diluted to equal to or greater than 3500 times.
Inactivation Study:
To evaluate successful inactivation of Influenza A virus, Influenza A H3N2 virus was combined at a ratio of 1:1 in negative nasal matrix mixed with Sample Preservative Fluid and incubated for 30 and 60 seconds. The initial concentration of the Influenza A H3N2 was >1x107 TCIDso/mL. Each mixture was then diluted 3500x (determined in the cytotoxicity study) with complete cell culture medium. Each dilution was plated into 8 wells of a 96-well cell culture plate in triplicate and incubated for 3-4 hours. The medium was removed and replaced with 100uL of complete cell culture medium. The plate was incubated at 34°C and 5% atmosphere for 4-7 days. The plate was observed for cytopathic effects and virus titers were calculated.
Additionally, positive controls containing Influenza A H3N2 virus and sterile saline were mixed at a ratio of 1:1 and incubated for 30 and 60 seconds. Each mixture was then diluted to 3500x (determined in the cytotoxicity study) with complete cell culture medium. Each dilution was plated into 8 wells of a 96-well cell culture plate in triplicate and incubated for 3-4 hours. The medium was removed and replaced with 100µL of complete cell culture medium. The plate was incubated at 34°C and 5% CO2 atmosphere for 4-7 days. The plate was observed for cytopathic effects and virus titers were calculated.
Negative controls were also evaluated as part of this study in which MDCK cells were incubated with complete cell culture medium 34°C and 5% CO2 atmosphere for 4-7 days. The plate was observed for cell growth and culture contamination.
No cytotoxicity was observed in the cell monolayer after exposure to Influenza A virus samples incubated in Sample Preservative Fluid for 30 or 60 seconds. The result was ≥4.7 logarithmic reduction in Influenza A after 30 and 60 seconds in the Sample Preservative Fluid. Therefore, the Sample Preservative Fluid inactivated Influenza A H3N2 in MDCK cells and the device demonstrated viral inactivation of >99.99%. Cytotoxicity was observed in the positive control group, and no viral infection was observed in the negative control group.
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9. Conclusions:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.