(942 days)
The Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution is intended for the collection, inactivation, preservation/stabilization, and transport of unprocessed upper respiratory clinical specimens from individuals suspected of influenza A infection by their healthcare provider. Specimens collected with the Sample Preservation Solution can be stored and transported at 4 °C or at room temperature (20-25°C) for preservation of microbial nucleic acid until the sample is processed and used with compatible molecular diagnostic assays.
The Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution consists of a plastic, polypropylene screw-cap collection tube filled with non-sterile sample preservation medium. The tubes are pre-filled with either 2 mL (suitable for swabs with flocking length of 20-24 mm) or 3 mL (suitable for swabs with flocking length of 24-30 mm) of solution. The device is nonsterile, for single use. Swabs are not included.
The provided document is a 510(k) summary for the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution, which is a microbial nucleic acid storage and stabilization device. It details the device's intended use, description, principles of operation, and a comparison to a predicate device. Crucially, it includes performance data related to shelf-life stability, limit of detection (LoD), nucleic acid stability, and viral inactivation.
However, the document does not describe acceptance criteria in the format of a table with specific thresholds and reported performance against those thresholds, nor does it detail a study proving the device meets acceptance criteria per se in the context of an AI/human-in-the-loop diagnostic system. This document is a regulatory submission demonstrating substantial equivalence for a medical device (a sample preservation solution), not for an AI algorithm or a diagnostic test involving human readers.
Therefore, many of the requested points are not applicable to the provided text. I will address the relevant points based on the information available in the document.
Acceptance Criteria and Device Performance (as inferred from the context of a sample preservation solution):
Since this is not an AI diagnostic device, the "acceptance criteria" here refer to the performance benchmarks demonstrated for the sample preservation solution itself, such as stability of the nucleic acid, effective viral inactivation, and physical/chemical stability over time.
Table of Acceptance Criteria and Reported Device Performance (Inferred):
| Criterion (Inferred from Study Goals) | Acceptance Threshold (Inferred) | Reported Device Performance |
|---|---|---|
| Shelf-life Stability | ||
| - Appearance | Good seal, no damage, leakage, or deformation; clean, clear, and complete label; consistent reagent color with no precipitation or impurities. | All lots tested at each time point passed the criteria for appearance when held at 20-25°C for 24 months. |
| - pH Stability | pH within 7.3 ± 0.2. | For all tubes at each time point and each lot, the pH was within the targeted range of 7.3 ± 0.2 when held at 20-25°C for 24 months. |
| - Evaporation | Actual volume no less than 97% of theoretical volume. | All lots tested at each time point passed the criteria for evaporation (up to >97% of loading volume) when held at 20-25°C for 24 months. |
| Limit of Detection (LoD) | 100% agreement for the determined LoD concentration. | Preliminary LoD determined to be 10^2 copies/mL. Confirmed by performing 20 replicates with 100% agreement (20/20 positive), average Ct value of 30.9 and SD of 0.94. |
| Nucleic Acid Stability | Average ΔCt from T₀ within +/- 3.0 Ct. | 4°C Storage: - 3 Day: -0.43 ΔCt - 6 Day: -2.76 ΔCt Room Temperature (20-25°C) Storage: - 3 Day: 0.57 ΔCt - 6 Day: 0.44 ΔCt All values met the +/- 3.0 Ct pre-defined acceptance criteria. Stability claimed for up to 6 days at both 4°C and room temperature. |
| Viral Inactivation | Inactivation leading to >4.0 log reduction in concentration (predicate's performance indicated) or a specific log reduction as determined to be effective. The document states "meeting the pre-defined acceptance criteria" for nucleic acid stability, implying a pre-defined target. | >6.2 log reduction in Influenza A concentration at 5 minutes (equivalent to >99.99% inactivation for all lots at 5 and 10 minutes). For Lot#1 and Lot#2, inactivation was already >6.97 log reduction at 0 minutes. For Lot#3, it was 3.28 log reduction at 0 minutes, but increased to >6.20 at 5 and 10 minutes. The conclusion states "inactivates Influenza A virus when incubated for at least 5 minutes." |
Regarding the specific points for AI/diagnostic studies:
1. Sample sized used for the test set and the data provenance:
- Test Set Description: The document describes performance testing for a sample preservation solution, not an AI model.
- LoD Study: 4 replicates for preliminary LoD determination at each of 5 concentrations; 20 replicates for LoD confirmation.
- Nucleic Acid Stability: Triplicate samples of 3 lots (total 9 samples per time point/temperature combination).
- Viral Inactivation: Triplicate samples of 3 lots (total 9 samples per time point/exposure time combination) for cytotoxicity; triplicate samples of 3 lots for Test, Positive, and Negative Control groups (total 27 samples per exposure time for viral inactivation).
- Data Provenance: Not explicitly stated beyond "upper respiratory matrix." It's not clinical patient data but rather spiked laboratory samples. No country of origin is mentioned for the data itself, only for the manufacturer (China). The study design is laboratory-based (spiking known quantities of virus).
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. Ground truth for these studies (LoD, nucleic acid stability, viral inactivation) is established by the known concentration of spiked virus and quantitative molecular assays (RT-PCR) or cell culture-based infectivity assays (TCID50), rather than expert human interpretation.
3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. This is not a study requiring human adjudication of images or clinical cases.
4. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. This is a performance study for a sample preservation solution, not a diagnostic device involving human readers or AI assistance.
5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not applicable. There is no algorithm being tested in this context. The "device" is a physical solution.
6. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Quantitative Laboratory Measurements: Ground truth is established by:
- Known concentrations of spiked Influenza A virus.
- RT-PCR Ct values: Quantitative measure of nucleic acid presence.
- TCID50 (Tissue Culture Infectious Dose 50%): Quantitative measure of live virus infectivity.
7. The sample size for the training set:
- Not applicable. There is no "training set" as this is not an AI/machine learning model.
8. How the ground truth for the training set was established:
- Not applicable. See point 7.
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Image /page/0/Picture/0 description: The image contains two logos. The logo on the left is the Department of Health & Human Services - USA logo. The logo on the right is the FDA U.S. Food & Drug Administration logo. The FDA logo is in blue.
April 8, 2024
Zhejiang GENE SCIENCE Co., Ltd. C/O Olivia Meng Regulatory Affairs Manager Guangzhou Osmunda Medical Device Technical Services Co.,Ltd. 8-9th Floor, R&D Building, No.26 Qinglan Street, Panyu District Guangzhou, Guangdong 510006, China
Re: K212878
Trade/Device Name: Sample preservation solution Regulation Number: 21 CFR 866.2950 Regulation Name: Microbial Nucleic Acid Storage And Stabilization Device Regulatory Class: Class II Product Code: QBD Dated: September 3, 2021 Received: September 9, 2021
Dear Olivia Meng:
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).
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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 (QS) 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 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,
Ribhi Shawar -S
Ribhi Shawar, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility 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) K212878
Device Name Sample Preservation Solution
Indications for Use (Describe)
The Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution is intended for the collection, inactivation, preservation/stabilization, and transport of unprocessed upper respiratory clinical specimens from individuals suspected of influenza A infection by their healthcare provider. Specimens collected with the Sample Preservation Solution can be stored and transported at 4 °C or at room temperature (20-25°C) for preservation of microbial nucleic acid until the sample is processed and used with compatible molecular diagnostic assays.
| 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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510(k) Summary - K212878
April 8, 2024
The following information is provided in accordance with 21 CFR 807.92 for the Premarket 510(k) Summary:
| Submitted by: | Zhejiang GENE SCIENCE Co., LtdNo.2 workshop, Pharmaceutical Industrial Park, No.11Shengxing Road, Shangyu Economic and TechnologicalDevelopment zone Hangzhou Bay, Zhejiang Province, ChinaTel: +86-575-82586086E-mail: support@gene-science-tech.comWebsite: http://www.gene-science-tech.com/ |
|---|---|
| Contact Person: | Olivia MengZhejiang GENE SCIENCE Co., Ltd.Tel: +86-188-25133860,Email: hui.meng@osmundacn.com |
| Name of Device: | Sample Preservation Solution |
| Classification Name: | Microbial Nucleic Acid Storage and Stabilization Device |
| Regulatory Class: | Class II |
| Product Code: | QBD |
| Regulation: | 21 CFR 866.2950 |
| Predicate Device: | Copan eNAT Molecular Collection and Preservation Medium(K201849) Manufacturer: Copan Diagnostics Inc. |
1. Intended Use/Indication for Use
The Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution is intended for the collection, inactivation, preservation/stabilization, and transport of unprocessed upper respiratory clinical specimens from individuals suspected of influenza A infection by their healthcare provider. Specimens collected with the Sample Preservation Solution can be stored and transported at 4 °C or at room temperature (20-25°C) for preservation of microbial nucleic acid until the sample is processed and used with compatible molecular diagnostic assays.
2. Device Description
The Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution consists of a plastic, polypropylene screw-cap collection tube filled with non-sterile sample preservation medium. The tubes are pre-filled with either 2 mL (suitable for swabs with flocking length of 20-24 mm) or 3 mL (suitable for swabs with flocking length of 24-30 mm) of solution. The device is nonsterile, for single use. Swabs are not included.
The Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution is offered in the following configurations:
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| SKU or Catalog Number | Device Description | Pack Size |
|---|---|---|
| YA-02 | 2.0 mL/tube | 100pcs/Tray, 15 Trays/Box |
| YA-03 | 3.0 mL/tube | 100pcs/Tray, 15 Trays/Box |
Media Formulation:
- Guanidine isothiocyanate
- EDTA
- Tris-HC1 ●
- Yeast RNA
- TWEEN-20
- Phenol red
- In vitro grade water
3. Principles of Operation
The Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution consists of the following: Guanidine isothiocyanate, EDTA, Tris-HCl, Yeast RNA, TWEEN-20, Phenol red and in vitro diagnostic grade water. The guanidine isothiocyanate lyses cells, denatures proteins, and inhibits nuclease activity, thereby stabilizes nucleic acids. EDTA is a chelating agent that deactivates RNAse and stabilizes RNA. Tris-HCl is a pH buffer system to maintain reagent pH. Yeast RNA serves as a blocking agent, protects RNA, helps coprecipitating microbial nucleic acid. TWEEN-20 is a detergent that disrupts membranes and denatures proteins. Phenol red is a pH indicator which serves as a visual quality control mechanism. The in vitro diagnostic grade water serves as a diluent to adjust molarity of the buffer/preservation medium.
4. Substantial Equivalence
The Zhejiang GENE SCIENCE Co., Ltd. Sample Preservation Solution is compared with the predicate device, Copan eNAT Molecular Collection and Preservation Medium (K201849). , in intended use, medium formulation, product configuration, shelf life, packaging and volume, etc. The safety and effectiveness of the Zhejiang GENE SCIENCE Co., Ltd. Sample Preservation Solution is adequately supported by the substantial equivalence information and testing results provided. Below is a summary of comparison table between Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution and predicate device K201849:
| Device & PredicateDevice(s): | Subject Device:K212878 | Predicate:K201849 |
|---|---|---|
| Device Trade Name | Sample PreservationSolution | Copan eNAT MolecularCollection andPreservation Medium |
| General DeviceCharacteristic Similarities | ||
| Indications For Use | The Zhejiang GENESCIENCE Co., Ltd.'sSample PreservationSolution is intended forthe collection.inactivation,preservation/stabilization, and transport ofunprocessed upperrespiratory clinicalspecimens fromindividuals suspected ofinfluenza A infection bytheir healthcareprovider. Specimenscollected with theSample PreservationSolution can be storedand transported at 4°Cor at room temperature(20-25°C) forpreservation ofmicrobial nucleic aciduntil the sample isprocessed and used withcompatible moleculardiagnostic assays. | Copan eNAT isintended for thecollection, inactivationand transport of clinicalspecimens containinginfluenza A virusesfrom the collection siteto the testing laboratory.eNAT can be processedand used withcompatible molecularassays that requirestabilization of nucleicacids from influenza Aviruses. |
| Microorganism nucleicacids preserved | Influenza A virus | Same |
| Specimen Type | Upper respiratoryspecimens | Same |
| General DeviceCharacteristic Differences | ||
| Specimen stability | Preserves influenza ARNA for up to 6 days at4-25 °C | Preserves influenza ARNA for up to 28 daysat 2-25°C |
| Ingredients | Guanidineisothiocyanate | Tris-EDTA |
| EDTA | Guanidine thiocyanate | |
| Tris-HCl | Detergent | |
| Yeast RNA | HEPES | |
| TWEEN-20 | Distilled water | |
| Phenol red | ||
| In Vitro Diagnosticgrade water | ||
| Inactivation of Flu A | >6.2 log reduction inconcentration at 5minutes | >4.0 log reduction inconcentration at 10seconds |
| Configurations of device | 2mL or 3mL | 2mL with either noswab, regular sized tipnylon flocked swab orminitip nylon flockedswab. |
| Shelf-life | 24 months | 18 months |
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5. Shelf-life Stability
The shelf-life of the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution was determined to be 24 months from the date of manufacture when stored at 20-25 ℃.
Three lots of the product were assessed for functionality and physical characteristics using real time ageing studies. In the real time study, the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solutions were held at 20-25 ℃ for 24 months (T= 0, 1, 3, 6, 12, 15, 18, 21, and 24). At each time point, appearance, pH and loading volume were assessed for each product lot in triplicate.
-
a) Appearance
To evaluate appearance, the different lots of the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution were visually examined. The appearance of the product was examined for a good seal of the packaging, no damage, leakage, or deformation; the label was clean, clear, and complete; the color of the reagent was consistent with no precipitation or impurities. All lots tested at each time point passed the criteria for appearance when held at 20-25°C. -
b) pH Stability
The pH of the media was used as one of the indicators to support product stability. For all the tubes at each time point and each lot, the pH was within the targeted range of 7.3±0.2 when held at 20-25°C.
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- c) Evaporation
To evaluate evaporation, the loading volume for the different lots of the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution were measured. All lots tested at each time point passed the criteria for evaporation (up to >97% of loading volume) when held at 20-25°C.
The Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution results after 24 months of storage showed that the actual volume was no less than 97% of the theoretical volume, the appearance was acceptable, and the pH was 7.3+ 0.2. There was no leakage or deformation, showing that the product met quality standards.
6. Performance Data
Limit of Detection (LoD) Study:
The limit of detection (LoD) for the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution (3mL/tube) was determined by spiking Influenza A virus (National Institutes for Food and Drug Control; Catalog numbers: 370051-201801) at a starting concentration of ≥ 1 x 107 copies/mL into upper respiratory matrix and inoculated into Sample Preservation Solution for a final concentration of 1 x 10° copies/mL. The spiked sample was then serially diluted in negative upper respiratory matrix to create five (5) concentrations (10°, 10°, 10° and 10 copies/mL). Each concentration was tested in four (4) replicates. Samples were extracted with the Oiagen RNeasy Mini Kit and RT-PCR was performed using the Invitrogen SuperScript III Platinum One-Step Quantitative Kit on the ThermoFisher ABI 7500 Instrument. The preliminary LoD was determined to be 102 copies/mL and confirmed by performing 20 replicates with a 100% agreement, average Ct value was 30.9 with a SD of 0.94. (Table 1-2).
| ThermoFisherABI 7500Instrument | Concentration (cp/mL)(Ct <40) | ||||
|---|---|---|---|---|---|
| 105 | 104 | 103 | 102 | 101 | |
| 1 | 27 | 28 | 31 | 33 | 40 |
| 2 | 24 | 28 | 31 | 32 | 40 |
| 3 | 25 | 27 | 32 | 37 | 42 |
| 4 | 24 | 29 | 31 | 35 | 39 |
| Total Positive | 4/4 | 4/4 | 4/4 | 4/4 | 1/4 |
| Table 1: Preliminary LoD Determination | ||
|---|---|---|
Table 2: Confirmation of LoD
| ThermoFisherABI 7500Instrument | Influenza A(Ct<40) | Interpretation | TotalPositive/Tested |
|---|---|---|---|
| ---------------------------------------- | ------------------------ | ---------------- | -------------------------- |
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| (102copies/mL) | |||
|---|---|---|---|
| 1 | 31 | Positive | |
| 2 | 32 | Positive | |
| 3 | 31 | Positive | |
| 4 | 31 | Positive | |
| 5 | 31 | Positive | |
| 6 | 30 | Positive | |
| 7 | 31 | Positive | |
| 8 | 30 | Positive | |
| 9 | 31 | Positive | |
| 10 | 30 | Positive | |
| 11 | 31 | Positive | 20/20 |
| 12 | 32 | Positive | |
| 13 | 31 | Positive | |
| 14 | 31 | Positive | |
| 15 | 32 | Positive | |
| 16 | 31 | Positive | |
| 17 | 31 | Positive | |
| 18 | 29 | Positive | |
| 19 | 29 | Positive | |
| 20 | 33 | Positive | |
| Mean | 30.9 | ||
| SD | 0.94 |
Nucleic Acid Stability Testing:
To determine nucleic acid stability of the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution, three (3) lots of varying ages were examined. Triplicate samples of each lot were created by immersing upper respiratory samples into the Zhejiang GENE SCIENCE Co., Ltd. Sample Preservation Solution then spiking with influenza A virus to produce a concentration of 3 x LoD. Spiked samples were stored at 4±1℃ and room temperature (20-25°C) for 1. 3. and 6 days. Samples were then extracted with the Oiagen RNeasy Mini Kit and RT-PCR testing was performed using the Invitrogen SuperScript III Platinum One-Step Quantitative Kit on the ThermoFisher ABI 7500 Instrument. Average Ct values were calculated per lot at each time point. Comparison of values obtained at each time point to the average To values indicated similar results regardless of the lot age. Overall, when results of all lots were combined a decrease in the Ct values of 0.43 and of 2.76 Ct was observed for the samples stored at 4±1℃ for 3 and 6 days, respectively (Table-3). For the samples stored at room temperature (20-25°C), an increase in the Ct values of 0.57 and 0.44 was observed for the samples stored for 3 and 6 days, respectively, meeting the pre-defined acceptance criteria of (+/-) 3.0 Ct from the initial time zero value (Table-3).
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| Time | 4 °C | Room temperature(20-25 °C) | ||
|---|---|---|---|---|
| Average Ct(Mean ± SD) | Average Δ Ctfrom T₀ | Average Ct(Mean ± SD) | Average Δ Ctfrom T₀ | |
| 0 | 35.43 ± 0.38 | N/A | 35.43 ± 0.75 | N/A |
| 3 Day | 35.0 ± 0 | -0.43 | 36.0 ± 0.73 | 0.57 |
| 6 Day | 32.67 ± 0.35 | -2.76 | 35.87± 1.8 | 0.44 |
| Table 3: Influenza A nucleic acid Stability in Sample Preservation Solution* | ||
|---|---|---|
- Data for all age lots were combined since no differences were noted.
Overall, the study results support the Influenza A nucleic acid stability claim of the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution for up to 6 days at 4°C and at room temperature (20-25°C).
Viral Inactivation:
A viral inactivation study was conducted to test the ability of GENE SCIENCE Co., Ltd.'s Sample Preservation Solution to inactivate Influenza A virus.
- a. Cytotoxicity: To determine cytotoxicity of the Zhejiang GENE SCIENCE Co., Ltd. Sample Preservation Solution, three (3) lots at varying ages were examined. Each sample preservation solution was serially diluted with diluent to create 2, 4, 8, 16, 32, 64, and 128-fold dilutions. Each dilution was inoculated to cell monolayers in triplicate and examined for Cytopathic Effect (CPE). The lowest dilution to indicate normal cell growth was determined to be the 64-fold dilution.
- b. Viral Inactivation: To determine the degree of viral inactivation produced by the Zhejiang GENE SCIENCE Co., Ltd. Sample Preservation Solution, three (3) lots of varying ages were examined. Upper respiratory matrix in saline was spiked with ≥107 copies per mL of influenza A virus (A/PR/8/34 H1N1) in a 1:1 suspension to create spiked upper respiratory swab samples for the following three groups.
- i. Test Group (Ct): Using a new swab, spiked upper respiratory swab samples (~0.08 mL) were inserted into the collection device with 3mL of Sample Preservation Solution. They were then exposed for 0, 5, and 10 minutes. At the end of the exposure, samples were diluted 1:64 which was determined not to be toxic to the cell culture monolayer, inoculated onto the host cell monolayers, incubated 7 days, observed daily for CPE. The remaining infectivity (log TCID50) was calculated and corrected using a dilution factor to account for the 1:64 dilution of Sample Preservation Solution to the diluent Medium to avoid cytotoxicity (dilution factor is 1.81 log) and the initial dilution of 0.08 ml into 3.08 ml (dilution factor is 1.58 log).
- ii. Positive Control Group (Co): Using a new swab, spiked upper respiratory samples (~0.08 mL) were inserted into a collection tube containing 3 mL of diluent (0.85% saline). They were then exposed for 0, 5, and 10 minutes. At the
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end of the exposure, samples were diluted 1:64 which was determined not to be toxic to the cell culture monolayer, inoculated onto the host cell monolayers, incubated 7 days, and observed daily for CPE. Log TCID50 was calculated and corrected using the dilution factors described above.
- iii. Negative Control Group (Cn): Upper respiratory swab samples (~0.08 mL) were inserted into the collection device with 3 mL Sample Preservation Solution and exposed for 0, 5, and 10 minutes. At the end of the exposure, samples were diluted 1:64 which was determined not to be toxic to the cell culture monolayer, inoculated onto the host cell monolayers, incubated 7 days, observed daily for CPE. No CPE was observed, confirming that he 1:64 dilution eliminated the cell toxicity produced by the Sample Preservation Solution.
Using the Inactivation (log reduction) formula below, Influenza A viral inactivation rate of Zhejiang GENE SCIENCE Co., Ltd's. Sample Preservation Solution was determined to be >6.2 log reduction at 5 minutes which was equivalent to greater than 99.99% inactivation of Influenza A virus (Table 4).
Inactivation (log reduction): Mv = log (C0/Ct) = log(C0)-log (Ct)
| Time(min) | Inactivation (log reduction, Mv) | ||
|---|---|---|---|
| Lot#1 | Lot#2 | Lot#3 | |
| 0 | >6.97 | >6.97 | 3.28 |
| 5 | >6.20 | >6.20 | >6.20 |
| 10 | >6.75 | >6.75 | >6.75 |
Table 4: Influenza A Viral Inactivation in Sample Preservation Solution
Conclusion:
Zhejiang GENE SCIENCE Co., Ltd's. Sample Preservation Solution inactivates Influenza A virus when incubated for at least 5 minutes.
7. Final Conclusion
Based on the indications for use, technological characteristics, safety, and performance testing, the subject device, the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution, meets the requirements that are considered essential for its intended use and is substantially equivalent to the legally marketed predicate device, Copan eNAT Molecular Collection and Preservation Medium, K201849.
§ 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.