← Product Code [QBD](/submissions/MI/subpart-c%E2%80%94microbiology-devices/QBD) · K212878

# Sample preservation solution (K212878)

_Zhejiang Gene Science Co., Ltd. · QBD · Apr 8, 2024 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-c%E2%80%94microbiology-devices/QBD/K212878

## Device Facts

- **Applicant:** Zhejiang Gene Science Co., Ltd.
- **Product Code:** [QBD](/submissions/MI/subpart-c%E2%80%94microbiology-devices/QBD.md)
- **Decision Date:** Apr 8, 2024
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.2950
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications 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.

## Device Story

Device is a non-sterile, single-use polypropylene collection tube pre-filled with 2 mL or 3 mL of preservation medium. Input: unprocessed upper respiratory clinical specimens (swabs). Operation: chemical lysis and stabilization via guanidine isothiocyanate, EDTA, Tris-HCl, yeast RNA, TWEEN-20, and phenol red. Device inactivates influenza A virus and stabilizes viral RNA for transport/storage at 4-25°C. Used by healthcare providers in clinical settings. Output: stabilized specimen for downstream molecular diagnostic assays. Benefits: enables safe handling of potentially infectious samples and preserves nucleic acid integrity for accurate diagnostic testing.

## Clinical Evidence

No clinical data. Bench testing only. Viral inactivation study demonstrated >6.2 log reduction of influenza A virus at 5 minutes. Nucleic acid stability study confirmed stability of influenza A RNA for 6 days at 4°C and room temperature (20-25°C), with Ct value changes within ±3.0 of T₀. Limit of Detection (LoD) confirmed at 10² copies/mL with 100% positivity agreement.

## Technological Characteristics

Polypropylene screw-cap collection tube; 2 mL or 3 mL fill volumes. Chemical composition: guanidine isothiocyanate, EDTA, Tris-HCl, yeast RNA, TWEEN-20, phenol red, and in vitro diagnostic grade water. Non-sterile, single-use. Shelf-life: 24 months at 20-25°C.

## Regulatory 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.

## Special Controls

The special controls for this device are: (1) The intended use for the 21 CFR 809.10 labeling must include a detailed description of microorganisms and types of human specimens intended to be preserved. (2) The 21 CFR 809.10(b) labeling must include: (i) A detailed device description, including all device components. (ii) Performance characteristics from applicable analytical studies, including but not limited to, 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. (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, but not limited to, extraction platforms and assays used for the detection of preserved nucleic acids. (iii) The limit of detection (LoD) of the molecular test used to establish microorganism nucleic acid stability.

*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.

## Predicate Devices

- Copan eNAT Molecular Collection and Preservation Medium ([K201849](/device/K201849.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K212878

B Applicant

Zhejiang GENE SCIENCE Co., Ltd.

C Proprietary and Established Names

Sample preservation solution

D Regulatory Information

|  Product Code(s) | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  QBD | Class II | 21 CFR 866.2950 - Microbial Nucleic Acid Storage And Stabilization Device | MI - Microbiology  |

## II Submission/Device Overview:

A Purpose for Submission:

To obtain a substantial equivalence determination for the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution for the collection, inactivation, preservation/ stabilization, and transport of unprocessed upper respiratory clinical specimens containing influenza A virus.

B Measurand:

Inactivation of viral particles and stabilization of nucleic acids from influenza A virus upon storage in the subject device.

C Type of Test:

Microbial Inactivation and Nucleic Acid Stability assays

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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K212878 - Page 2 of 9

# III Intended Use/Indications for Use:

## A Intended Use(s):

See Indications for Use below.

## B Indication(s) 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.

## C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

## D Special Instrument Requirements:

Not Applicable

# IV Device/System Characteristics:

## A 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 non-sterile, single use. Swabs are not included.

The Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution is offered in the following configurations:

|  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  |

## B Principle 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 stabilizing 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 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

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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.

V Substantial Equivalence Information:

A Predicate Device Name(s):

eNAT molecular collection and preservation medium

B Predicate 510(k) Number(s):

K201849

C Comparison with Predicate(s):

|  Device & Predicate Device(s): | Subject Device: K212878 | Predicate: K201849  |
| --- | --- | --- |
|  Device Trade Name | Sample Preservation Solution | Copan eNAT Molecular Collection and Preservation Medium  |
|  General Device Characteristic Similarities |  |   |
|  Intended Use/Indications 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. | Copan eNAT is intended for the collection, inactivation and transport of clinical specimens containing influenza A viruses from the collection site to the testing laboratory. eNAT can be processed and used with compatible molecular assays that require stabilization of nucleic acids from influenza A viruses.  |
|  Specimen Type | Upper respiratory specimens | Same  |

K212878 - Page 3 of 9

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|  Analyte tested | Influenza A | Same  |
| --- | --- | --- |
|  Single Use Device | Yes | Same  |
|  General Device Characteristic Differences |  |   |
|  Ingredients | Guanidine isothiocyanate
EDTA
Tris-HCl
Yeast RNA
TWEEN-20
Phenol red
In Vitro Diagnostic grade water | Tris-EDTA
Guanidine thiocyanate
Detergent
HEPES
Distilled water  |
|  Specimen stability | Preserves influenza A RNA for up to 6 days at 4-25 °C | Preserves influenza A RNA for up to 28 days at 2-25°C  |
|  Inactivation of influenza A | >6.2 log reduction in concentration at 5 minutes | >4.0 log reduction in concentration at 10 seconds  |
|  Shelf-life | 24 months | 18 months  |

VI Standards/Guidance Documents Referenced:

Special controls that are applicable to regulation 21 CFR 866.2950.

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:
Not Applicable

2. Linearity:
Not Applicable.

3. Analytical Specificity/Interference:
Not Applicable.

4. Assay Reportable Range:
Not Applicable.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

K212878 - Page 4 of 9

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# Shelf Life:

Three lots of  $3\mathrm{mL}$  specification of the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution device were used to conduct the following studies to evaluate physical characteristics. The product was assessed qualitatively at each time point to determine agreement with specifications for appearance (packaging has good seal, no damage, leakage, or deformation; the label is clean, clear, and complete; the color of the reagent is consistent, no precipitation, no impurities). Additionally,  $\mathsf{pH}$  and evaporation were assessed to confirm the  $\mathsf{pH}$  of  $(7.3 + 0.2)$  and a limit of evaporation up to  $\geq 97\%$  of the loading volume. The product met these acceptance criteria under all conditions.

The shelf-life of the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution was assessed by storing three lots of the product at room temperature  $(20 - 25^{\circ}\mathrm{C})$  for 0, 1, 3, 6, 12, 15, 18, 21, and 24 months in their Finished Product warehouse to test the real storage environment. At each time point, appearance, pH and loading volume were assessed for each product lot in triplicate and test results met the quality requirements. 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 the predefined quality standards.

# 6. Detection Limit:

To determine the Limit of Detection (LoD) of H1N1 influenza A virus stored in the Sample preservation solution, an LoD study was conducted using a validated RT-PCR assay. In brief, a serial dilution of contrived H1N1 influenza A virus samples were prepared by spiking the virus into human upper respiratory matrix and Sample Preservation Solution into five groups of final concentration  $(10^{5}, 10^{4}, 10^{3}, 10^{2}$  and 10 copies/mL). Each concentration was tested in 4 replicates to establish the preliminary LoD. Samples were extracted with the Qiagen 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  $10^{2}$  copies/mL and confirmed by performing 20 replicates with a  $100\%$  positivity agreement, average Ct value was 30.9 with a SD of 0.94. (Table 1-2).

Table 1: Preliminary LoD Determination

|  Replicates | Concentration (copies/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  |

K212878 - Page 5 of 9

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Table 2: Confirmation of LoD

|  ThermoFisher ABI 7500 Instrument (10² copies/mL) | Influenza A (Ct<40) | Interpretation | Total Positive/Tested  |
| --- | --- | --- | --- |
|  1 | 31 | Positive | 20/20  |
|  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  |   |
|  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  |   |   |

7. Nucleic Acid Sample Stability:

To determine nucleic acid stability of the Zhejiang GENE SCIENCE Co., Ltd.'s Sample Preservation Solution, three lots of Sample Preservation Solution of varying ages (one month, and two various age lots near expiration) were tested. Contrived swabs samples were prepared by spiking with 3 x LoD influenza A in negative upper respiratory swab matrix. Triplicate contrived swab samples were immersed into the Sample Preservation Solution and incubated for time 0, 3 day and 6 days at 4±1°C and room temperature (20-25°C) for each lot of Sample Preservation Solution. At the end of each time point samples were extracted with the Qiagen 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 T₀ 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°C 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).

K212878 - Page 6 of 9

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Table 3: Influenza A nucleic acid Stability in Sample Preservation Solution*

|  Time | 4 °C |   | Room temperature (20-25 °C)  |   |
| --- | --- | --- | --- | --- |
|   |  Average Ct (Mean ± SD) | Average Δ Ct from T₀ | Average Ct (Mean ± SD) | Average Δ Ct from 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  |

*Data for all age lots were combined since no differences were noted.

Overall, the nucleic acid study results support the ability of Zhejiang GENE SCIENCE Co., Ltd.’s Sample Preservation Solution to stabilize the Influenzas A RNA up to 6 days at 4°C and room temperature (20-25°C)

8. 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 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 (i.e., no cytotoxicity) 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 3 mL 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 (C₀): 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 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,

K212878 - Page 7 of 9

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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 matrix only 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 &gt;6.2 log reduction at 5 minutes which was equivalent to greater than 99.99% inactivation Influenza A virus (Table 4).

Inactivation (log reduction): Mv = log (C0/Ct) = log(C0)-log (Ct)

Table 4: Influenza A Viral Inactivation in Sample Preservation Solution
|  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  |

Conclusion:
Zhejiang GENE SCIENCE Co., Ltd’s. Sample Preservation Solution inactivates Influenza A virus when incubated for at least 5 minutes.

9. Assay Cut-Off:
Not Applicable.

B Comparison Studies:

1. Method Comparison with Predicate Device:
Not Applicable.

2. Matrix Comparison:
Not Applicable.

K212878 - Page 8 of 9

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C Clinical Studies:

1. Clinical Sensitivity:
Not Applicable.

2. Clinical Specificity:
Not Applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not Applicable.

D Clinical Cut-Off:
Not Applicable.

E Expected Values/Reference Range:
Not Applicable.

VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

K212878 - Page 9 of 9

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**Source:** [https://fda.innolitics.com/submissions/MI/subpart-c%E2%80%94microbiology-devices/QBD/K212878](https://fda.innolitics.com/submissions/MI/subpart-c%E2%80%94microbiology-devices/QBD/K212878)

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