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.

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)

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the Sample Preservative Fluid, based on the provided document:

Acceptance Criteria and Device Performance

Acceptance Criteria	Reported Device Performance
Shelf-life:	Shelf-life:
No bacterial or fungal growth	No bacterial or fungal growth observed for 24 months.
No obvious change in appearance	No change in appearance observed for 24 months.
No tube leakage at -0.08 MPa for ten minutes	No tube leakage observed for 24 months.
Media density of 1.06 ± 0.04 g/mL	No change in density over time observed for 24 months.
Detection Limit (LoD):	Detection Limit (LoD):
Lowest concentration detected with ≥ 95% detection rate	0.08 TCID50/mL for Influenza A H3N2 (A/California/2/2014, VR-1938) with 100% detection rate.
Specimen Stability:	Specimen Stability:
All Ct values fall within a 3.0 Ct range of Day 0	All Ct values for Influenza A H3N2 in nasal matrix preserved at 2-4°C and 20-25°C for 35 days fell within a 3.0 Ct range of Day 0, indicating no significant degradation.
Cytotoxicity (for viral inactivation assay):	Cytotoxicity (for viral inactivation assay):
No significant cytotoxicity to cell monolayer	No toxicity to MDCK cell monolayer observed when Sample Preservative Fluid was diluted to ≥ 1:3500. A 1:4000 dilution showed normal cell morphology/growth in preliminary tests, and 1:3500 in confirmatory tests.
Viral Inactivation:	Viral Inactivation:
Successful inactivation of Influenza A virus	≥4.7 logarithmic reduction in Influenza A after 30 and 60 seconds of incubation in the Sample Preservative Fluid, demonstrating viral inactivation of >99.99%. No cytotoxicity observed in the cell monolayer from samples exposed to inactivated virus.

Study Details

Sample size used for the test set and the data provenance:
- Shelf-life: 3 lots of Sample Preservative Fluid. Data provenance is not explicitly stated but is implicitly from an in-house study conducted by the applicant (Hangzhou Bioer Technology Co., Ltd). The study appears to be proprietary/internal rather than retrospective or prospective clinical data.
- Detection Limit (LoD):
  - Preliminary LoD: 5 replicates for each of 5 concentrations (0.32, 0.16, 0.08, 0.04, 0.02, 0.01 TCID50/mL) for a total of 30 replicates (though actual testing for 0.02 and 0.01 TCID50/mL ceased if a certain number of negative results were observed).
  - Confirmatory LoD: 20 replicates at 0.08 TCID50/mL (initially attempted at 0.04 TCID50/mL).
  - Data provenance is from an in-house laboratory study.
- Specimen Stability: Replicates of four for each of three reagent lots, tested at 6 timepoints (Day 0, 1, 8, 15, 22, 35) at two different temperatures (2-4°C and 20-25°C). Total number of Ct values reported is 144 for each temperature condition (3 lots * 4 reps * 6 timepoints). Data provenance is from an in-house laboratory study.
- Cytotoxicity Study: Not explicitly stated, but multiple dilutions (from 1:10 up to 1:8000 for preliminary, and from 1:1000 for confirmatory) were tested against a cell monolayer. This is an in-house laboratory study.
- Viral Inactivation Study: Influenza A H3N2 virus combined with Sample Preservative Fluid and negative nasal matrix, incubated for 30 and 60 seconds. Each mixture diluted 3500x and plated into 8 wells in triplicate (total of 24 wells per condition). Positive and negative controls were also used. This is an in-house laboratory study.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. The studies described are laboratory-based performance studies (shelf-life, LoD, stability, inactivation) using controlled experimental conditions and quantitative measurements (e.g., bacterial/fungal growth, leakage, density, PCR Ct values, viral titers, cell morphology), not expert interpretation of clinical data.
Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not applicable, as expert adjudication is not used for these types of laboratory performance studies.
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 device is a sample preservative fluid, not an AI-powered diagnostic or imaging system involving human readers.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: Not applicable. This is a physical device (fluid) and does not involve an algorithm.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Shelf-life: Physical and chemical property evaluations (e.g., visual inspection, pressure tests, density measurements) and microbial growth assays.
- Detection Limit (LoD): Defined concentration of target virus (Influenza A H3N2) in negative nasal matrix, assayed by a cleared molecular diagnostic device (Cepheid Xpert Xpress Flu/RSV Assay).
- Specimen Stability: Defined concentration of target virus (Influenza A H3N2) in negative nasal matrix, assayed by a cleared molecular diagnostic device (Cepheid Xpert Xpress Flu/RSV Assay). Comparison of Ct values over time to a baseline (Day 0).
- Cytotoxicity Study: Observation of cell morphology and growth status on a cell monolayer (MDCK cells).
- Viral Inactivation Study: Measurement of viral titers (TCID50/mL) and observation of cytopathic effects on MDCK cells. Reduction in culturable virus compared to controls.
The sample size for the training set: Not applicable. This device does not use machine learning or AI, and therefore does not have a training set.
How the ground truth for the training set was established: Not applicable, as there is no training set.

Summary

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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).

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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 (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

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Indications for Use

510(k) Number (if known) K222771

Device Name Sample Preservative Fluid

Indications for Use (Describe)

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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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'SREPUBLIC OF CHINA
Phone No.	+86-571-87774567
Contact person	Zoey ZhangRA Department
Contact person'se-mail	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'se-mail	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 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 Fluidis intended for the stabilization,transportation, and inactivationof infectious, unprocessed,upper respiratory specimenssuspected of containingInfluenza A virus. Specimenstransported in the SamplePreservative Fluid are stablerefrigerated (2-8°C) and atroom temperature (20-25°C).The Sample Preservative Fluidis suitable for use withcompatible legally marketedmolecular diagnostic devices.	PrimeStore MTM is intendedfor the stabilization,transportation and inactivationof infectious unprocessednasal washes suspected ofcontaining Influenza A virusRNA. PrimeStore MTM is alsointended for the stabilization,transportation and inactivationof infectious unprocessedsputum samples suspected ofcontaining Mycobacteriumtuberculosis DNA from humansamples.
Specimen storagetemperature	2-25 °C	2-25 °C
Shelf-life	24 months	24 months
General Device Characteristic Differences
Microorganismnucleic acidspreserved	Influenza A virus	Influenza A virus andMycobacterium tuberculosis
Specimen type	Upper respiratory specimens	Nasal washes and sputumsamples
Analyte	RNA	DNA, RNA
Specimen stability	2-25 °C ≤ 35 days	For Influenza A virus:4 °C ≤ 29 days27 °C ≤ 8 days

Non-clinical Testing 7.

7.1 Shelf-life:

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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 AConcentration(TCID50/mL)	Rep 1(Ct)	Rep 2(Ct)	Rep 3(Ct)	Rep 4(Ct)	Rep 5(Ct)	Avg(Ct)	SD(Ct)	CV(%)	DetectionRate (%)
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:

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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	0.300	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/mLInfluenza 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)
----------	-----	-----	-----------	-----------	-----------	------------	------------	------------

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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/mLInfluenza A innasal 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/mLInfluenza A innasal 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

{8}------------------------------------------------

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.

Regulation Number and Section

§ 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.