(262 days)
Not Found
No
The device is a molecular transport media for sample collection and stabilization, not a diagnostic or analytical device that would typically incorporate AI/ML for data processing or interpretation. The summary focuses on the chemical composition and performance characteristics related to sample preservation and inactivation.
No
Explanation: The device is intended for the stabilization, collection, transport, and storage of specimens for diagnostic testing, not for treating a condition or disease.
No
The device is a molecular transport medium (MTM) intended for the stabilization, transport, and direct lysis of nasopharyngeal samples. It is explicitly stated that "Specimens collected and stored in a Molecular Transport Media are suitable for use with legally marketed molecular diagnostic devices," indicating that the MTM itself is not a diagnostic device but rather facilitates the use of other diagnostic devices.
No
The device description clearly states it consists of a "pre-filled plastic tube containing either 2 or 3 mL of proprietary liquid medium". This describes a physical, hardware component (the tube and the liquid medium), not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device is for the "stabilization, and direct lysis of infectious unprocessed nasopharyngeal samples suspected of containing SARS COV-2 virus RNA." It also states that specimens collected and stored in this media are "suitable for use with legally marketed molecular diagnostic devices." This clearly indicates the device is intended to be used in vitro (outside the body) to prepare a sample for a diagnostic test.
- Device Description: The description details the components of the media and its purpose in stabilizing and inactivating viral nucleic acid for use with "standard diagnostic/identification techniques."
- Performance Studies: The document describes analytical performance studies (Limit of Detection, Viral Nucleic Acid Stability, Viral Inactivation) which are typical studies conducted for IVD devices to demonstrate their analytical performance characteristics.
- Predicate Device: The mention of a predicate device (K212113 - MagXtract Collection Tube) which is also a collection and transport device for molecular diagnostics further supports its classification as an IVD.
While the device itself doesn't perform the final diagnostic test (it's a sample preparation and transport media), it is an essential component in the overall in vitro diagnostic process for detecting SARS-CoV-2 RNA.
N/A
Intended Use / Indications for Use
The Molecular Transport Media - MTM is intended for the stabilization, and direct lysis of infectious unprocessed nasopharyngeal samples suspected of containing SARS COV-2 virus RNA. These devices can be used for the collection transport and storage of specimens at 15-35 °C. Specimens collected and stored in a Molecular Transport Media are suitable for use with legally marketed molecular diagnostic devices.
Product codes (comma separated list FDA assigned to the subject device)
QBD
Device Description
The MTM consists of a pre-filled plastic tube containing either 2 or 3 mL of proprietary liquid medium intended for viral nucleic acid stabilization and transportation and inactivation of nasopharyngeal swab specimens suspected of containing SARS-CoV-2. MTM is intended for use with standard diagnostic/identification techniques that have been adequately validated and found to be compatible with the MTM. The formulation of the MTM includes guanidine-free inactivation buffer, salts, a buffer to maintain a neutral pH, and distilled water.
The MTM maintains the integrity of SARS-CoV-2 viral nucleic acid when properly stored. Prior to use, vials should be stored at 15-35℃ for up to 18 months. After collection, the transport tube containing the specimen can be stored at 15-35℃ for up to 21 days, for transportation to the laboratory and storage.
The MTM is available in the following configurations:
- 50 vials with 3 mL of Molecular Transport Media (Catalog Number: o MEI00211)
- 50 vials with 2 mL of Molecular Transport Media (Catalog Number: ● MEI00283)
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasopharyngeal samples / Upper human respiratory
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 (study type, sample size, AUC, MRMC, standalone performance, key results)
Shelf life study: The shelf-life for the ALB Luz Molecular Transport Media - MTM was established to be 18 months from the date of manufacture when stored in a clean, dry, ventilated environment at 15-35°C. The shelf-life study was conducted by using a real-time aging performance test for 18 months. In this study, the shelf life was evaluated for physical stability (appearance) and pH stability during the period of storage.
- Physical Stability: To evaluate physical stability, any changes in appearance color, and turbidity of the MTM were physically or visually examined at storage time points T = 0, 3, 6, 9, 12, 15 and 18 months. Three lots with three replicates per lot at each timepoint were tested for physical stability at storage conditions of 15°C and 35°C. At each time point, the appearance of the product was inspected visually as colorless and clear liquid, without having precipitate.
- pH Stability: To evaluate product stability, the pH of the MTM was tested at storage time points T = 0, 3, 6, 9, 12, 15, and 18 months. Three lots with three replicates per lot at each time point were tested for pH stability at storage conditions of 15°C and 35°C. At each time point, the pH was measured by immersing the pH meter electrode into each MTM by adjusting the temperature to 25°C prior to testing. For all the tubes tested, the pH measurement was within the acceptable pH range of 8 +/- 1.
The results for physical stability and pH stability collectively support the 18month stability claim for the MTM for 18 months.
Limit of Detection Study: LoD testing was conducted to determine the lowest concentration of SARS-CoV-2 that contains measurable nucleic acids that can be repeatedly recovered from the transport media with a greater than 95% accuracy. The LoD was determined with in both preliminary and confirmatory studies.
- Preliminary LoD Study: A preliminary LoD study was conducted using a virus stock of SARS-CoV-2 and three pooled negative clinical nasal samples. Approximately 100 uL of each concentration (1.35E+05, 1.35E+04, 1.35E+03, 1.35E+02 and 1.35E+01 PFU/mL) was absorbed onto rayon swabs in triplicate. The swab was used to transfer each concentration of the virus and matrix into each lot of MTM at 15℃ and 35℃. SARS-CoV-2 RNA was extracted using MagMAX Viral/Pathogen Nucleic Acid Isolation Kit. Detection of SARS-CoV-2 RNA was conducted using the TaqPath COVID-19 Combo Kit (EUA200010) with the Applied Biosystems 7500 instrument. The preliminary LoD at SARS-CoV-2 concentration 1.35E+04 PFU the results were 3/3 for all targets. The concentration of 1.35E+03 PFU was determined to be the preliminary LoD for MTM at both 15°C and 35°C.
- Confirmatory LoD: The confirmatory study was determined with 20 replicates for SARS-CoV-2 at concentrations of 1.35E+04, 1.35E+03 and 1.35E+02 PFU. Each replicate was inoculated into each lot of MTM tubes and were tested as previously described. At a concentration of 1.35E+04 PFU the results were 20/20 for all targets. Based on the results, the confirmatory LoD for MTM is 1.35E+03 PFU.
Viral Nucleic Acid Stability Study: The SARS-CoV-2 virus stock (diluted to 6.00E+04 PFU/mL) were combined with pooled negative clinical nasal matrix in a 1:1 ratio resulting in a final concentration of 3.00E+04 PFU. Approximately 100 µL of this mixture was absorbed onto rayon swabs in triplicate at a final virus concentration of 3.00E+03 PFU. Each swab was transferred into three MTM tubes of each lot and incubated at 15°C or 35°C for the following time points: 0, 7, 14 and 21 days post-inoculation. At the end of each time point, SARS-CoV-2 RNA was extracted using MagMAX Viral/Pathogen Nucleic Acid Isolation Kit, analyzed using TaqPath COVID-19 Combo Kit and Applied Biosystems 7500 instrument. The MTM provided positive detection for all samples tested with Ct variation (ACt) less than ±3 Ct values for at least two of the three viral targets (ORF1ab, N gene and S gene) at time points 7, 14 and 21 days post-inoculation comparing to time point 0 for both 15°C and 35°C. Based on these study results, MTM is able to provide stability to the SARS-CoV-2 viral nucleic acid (i.e., RNA) for 21 days at both 15 and 35°C.
Viral Inactivation Study: A viral inactivation study was conducted to test the ability of MTM to inactivate SARS-CoV-2 virus.
- Cytotoxicity: A volume of 30 µL of each lot of MTM was transferred to a 24-well microplate containing 270 µL of Dulbecco's Modified Eagle Medium with 10% fetal bovine serum cell culture media (DMEM with 10% FBS) and serially diluted (10-fold) to obtain dilutions of 1:10E+01 to 1:10E+08 in triplicate. Next, 300 µL of each dilution was added onto confluent Vero cells and incubated at 37°C at 5% CO2 for 48 hours. Cytotoxicity was determined visually using an inverted microscope looking for Cytopathic Effect (CPE). The lowest dilution to indicate normal cell growth (i.e., no cytotoxicity) was determined to be the 1:10E+03 dilution in all lots at 15°C and 35°C of temperature storage. No cytotoxicity was observed for any of the dilutions from 1:10E+04 to 1:10E+08.
- Viral Inactivation: A volume of 75 µL of SARS-CoV-2 virus stock was mixed with 75 uL of pooled clinical negative nasal matrix in a 1:1 ratio to obtain a virus concentration of 1.35E+07 PFU/mL. Approximately 100 µL of this mixture was absorbed onto a rayon swab at a virus concentration of 1.35E+06 PFU and transferred into three tubes of each MTM lot number stored at 15°C and 35°C at time pointes of 0, 5 and 15-minutes post inoculation. No PFUs were obtained after the exposure times of 0, 5 and 15 minutes for all MTM lot numbers at 15℃ and 35℃. All the results appear to be acceptable and support SARS-CoV-2 inactivation at 5 minutes exposure with MTM at 15℃ and 35°C.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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 17, 2024
Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The FDA logo is composed of two parts: the Department of Health & Human Services logo on the left and the FDA text logo on the right. The text logo is in blue and reads "FDA U.S. FOOD & DRUG ADMINISTRATION".
ALB Luz % Graziela Brum Regulatory Affairs Specialist PR Servicos Regulatorios Administrativos Ltda Rua Alice Alem Saadi, 855/2402 Ribeirao Preto, Sao Paulo 14096-570 Brazil
Re: K233324
Trade/Device Name: Molecular Transport Media - MTM Regulation Number: 21 CFR 866.2950 Regulation Name: Microbial Nucleic Acid Storage And Stabilization Device Regulatory Class: Class II Product Code: QBD Dated: May 10, 2024 Received: May 10, 2024
Dear Graziela Brum:
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 OS 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
2
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K233324
Device Name
Molecular Transport Media - MTM
Indications for Use (Describe)
The Molecular Transport Media - MTM is intended for the stabilization, and direct lysis of infectious unprocessed nasopharyngeal samples suspected of containing SARS COV-2 virus RNA. These devices can be used for the collection transport and storage of specimens at 15-35 °C. Specimens collected and stored in a Molecular Transport Media are suitable for use with 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) |
|---|---|
| ----------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------ |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
"An agency may not conduct or sponsor and a person is not required to respond to a collection of
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
==============================================================================================================================================================================
Form Approved: OMB No. 0910-0120 Expiration Date: 07/31/2026 See PRA Statement below.
3
Molecular Transport Media – MTM
510(k) Summary: K233324
Administrative Information
| Sponsor | ALB LUZ Ltda.
Rua Um, 437
Valinhos, Sao Paulo, Brazil 3273-200
Telephone: +55 (19) 3849-7499 |
|--------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person and Preparer | Graziela Brum and Tatiana Jabor Botura
Regulatory Affairs Specialist
Passarini Regulatory Affairs
e-mail: graziela@passarini.com.br
Telephone: +55 (16) 3421 8488. |
| Data Prepared | May 08, 2024 |
| Device name and classification | |
| Trade Name | Molecular Transport Media – MTM |
| Common Name | Specimen Collection Tube |
| Regulation Number | 21 CFR 866.2950 |
| Regulatory Class | Class II |
| Product Code | QBD |
| Classification Panel | MI -Microbiology |
4
Device Description
Predicate Device: K212113 - MagXtract Collection Tube
Indications For Use
The Molecular Transport Media - MTM is intended for the stabilization, transportation, and direct lysis of infectious unprocessed nasopharyngeal samples suspected of containing SARS COV-2 virus RNA. These devices can be used for the collection transport and storage of specimens at 15-35 °C. Specimens collected and stored in a Molecular Transport Media are suitable for use with legally marketed molecular diagnostic devices.
Subiect Device Description
The MTM consists of a pre-filled plastic tube containing either 2 or 3 mL of proprietary liquid medium intended for viral nucleic acid stabilization and transportation and inactivation of nasopharyngeal swab specimens suspected of containing SARS-CoV-2. MTM is intended for use with standard diagnostic/identification techniques that have been adequately validated and found to be compatible with the MTM. The formulation of the MTM includes guanidine-free inactivation buffer, salts, a buffer to maintain a neutral pH, and distilled water.
The MTM maintains the integrity of SARS-CoV-2 viral nucleic acid when properly stored. Prior to use, vials should be stored at 15-35℃ for up to 18 months. After collection, the transport tube containing the specimen can be stored at 15-35℃ for up to 21 days, for transportation to the laboratory and storage.
The MTM is available in the following configurations:
- 50 vials with 3 mL of Molecular Transport Media (Catalog Number: o MEI00211)
- 50 vials with 2 mL of Molecular Transport Media (Catalog Number: ● MEI00283)
Technological Characteristics
The product is intended for use in the collection, inactivation, stabilization, transport, and preservation of SARS-CoV-2 viral nucleic acid from clinical samples collected from a rayon tipped nasopharyngeal swab. After sample collection, the swab is transferred into the tube of the MTM. Users then break the swab leaving the swab tip in the transport tube and screw the lid of the tube tightly.
The MTM is intended to disrupt/lyse cells and stabilize SARS-CoV-2 RNA. The preserved and stabilized SARS-CoV-2 RNA maintains its integrity for downstream molecular based detection/analysis. Samples should either be tested immediately or stored at 15-35℃ for up to 21 days.
The media contains the following reagents: ALB LUZ Ltda.
5
- Guanidine-free inactivation buffer
- Salts
- pH buffer solution ●
- Distilled water
Substantial Equivalence Information
As with the MagXtract Collection Tube, the MTM has a formulation that inactivates viral particles and stabilizes and preserves viral nucleic acid by guanidine-free inactivation buffer, salts, pH buffer, and distilled water.
The MTM is compared with the predicate device intended use, product configuration, and packaging. Besides the subject device and the predicate device having inactivation buffers, salts, and pH buffers that differ in the formula, all of them have the same action in disrupting viral particles and stabilizing viral RNA nucleic acid.
The safety and effectiveness of performance concerning the difference between shelf life and storage temperature are proven by the real-time age tests. The subject and predicate devices comparison is described in the table below:
| Device & Predicate
| Device(s): | Device: K233324 | Predicate: K212113 |
|---|---|---|
| Device Trade Name | Molecular Transport | |
| Media - MTM | MagXtract Collection | |
| Tube | ||
| General Device | ||
| Characteristic Similarities | ||
| Intended Use/Indications For | ||
| Use | The Molecular Transport | |
| Media - MTM is | ||
| intended for the | ||
| stabilization, | ||
| transportation, and direct | ||
| lysis of infectious | ||
| unprocessed | ||
| nasopharyngeal samples | ||
| suspected of containing | ||
| SARS-CoV-2 virus | ||
| RNA. These devices can | ||
| be used for the | ||
| collection, transport, and | ||
| storage of specimens at | ||
| 15-35°C. Specimens | ||
| collected and stored in a | ||
| Molecular Transport | ||
| Media are suitable for | ||
| use with legally | ||
| marketed molecular | The MagXtract | |
| collection tube collection | ||
| tube is intended for the | ||
| stabilization, | ||
| transportation, and direct | ||
| lysis of infectious | ||
| unprocessed | ||
| nasopharyngeal samples | ||
| suspected of containing | ||
| SARS-CoV-2 virus | ||
| RNA. These devices can | ||
| be used for collection, | ||
| transport, and storage of | ||
| specimens at refrigerated | ||
| (2-8°C) or ambient | ||
| temperatures (20-25°C). | ||
| Specimens collected and | ||
| stored in MagXtract | ||
| collection tube are | ||
| suitable for use with |
6
| | diagnostic devices. | legally marketed
molecular diagnostic
devices. |
|----------------------------------------------|-------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------|
| Sample Source | Same | Upper human respiratory |
| Specimen Type | Same | Nasopharyngeal swab
suspected of containing
SARS-CoV-2 |
| Nucleic Acid Preserved | Same | SARS-CoV-2 RNA |
| Inactivation Test | Same | Inactivates SARS-CoV-
2 virus |
| General Device
Characteristic Differences | | |
| Specimen Stability | The Molecular Transport
Media - MTM collection
tube preserves SARS-
CoV-2 RNA for up to 21
days at 15-35°C. | MagXtract collection
tube preserves SARS-
CoV-2 RNA for up to 5
days at 2-4°C and 20-
25°C. |
| Volume in Tube | 2 or 3 mL | 1.2 mL |
| Storage Temperature | 15-35°C | Refrigerated: 2-8°C
Ambient Temperatures
20-25°C |
| Shelf-Life | 18 months | 12 months |
Sterilization
MTM is not claimed to be sterile nor is it intended to be sterilized by the end user. These vials are single use devices. The manufacturing process includes sterilization of the polypropylene tubes prior to being filled by ethylene oxide (EO). Dispensing the MTM liquid into the tubes occurs in three steps: filtration, filling, and closing the tube.
Shelf life
The shelf-life for the ALB Luz Molecular Transport Media - MTM was established to be 18 months from the date of manufacture when stored in a clean, dry, ventilated environment at 15-35°C. The shelf-life study was conducted by using a real-time aging performance test for 18 months. In this study, the shelf life was evaluated for physical stability (appearance) and pH stability during the period of storage.
- i. MTM Lots Tested: The lot numbers utilized for the Shelf-Life Study are summarized in Table 1 below.
| Lot Number | Manufacture Date | Expiration Date |
|---|---|---|
| 10909040422MTM | 4/4/2022 | 10/4/2023 |
| 10910040422MTM | 4/4/2022 | 10/4/2023 |
| 02102022MTM | 10/2/2022 | 4/2/2024 |
Table 1: MTM Lot Numbers Utilized for Shelf-Life Study.
7
- Physical Stability: To evaluate physical stability, any changes in appearance color, ii. and turbidity of the MTM were physically or visually examined at storage time points T = 0, 3, 6, 9, 12, 15 and 18 months. Three lots with three replicates per lot at each timepoint were tested for physical stability at storage conditions of 15°C and 35°C. At each time point, the appearance of the product was inspected visually as colorless and clear liquid, without having precipitate.
- iii. pH Stability: To evaluate product stability, the pH of the MTM was tested at storage time points T = 0, 3, 6, 9, 12, 15, and 18 months. Three lots with three replicates per lot at each time point were tested for pH stability at storage conditions of 15°C and 35°C. At each time point, the pH was measured by immersing the pH meter electrode into each MTM by adjusting the temperature to 25°C prior to testing. For all the tubes tested, the pH measurement was within the acceptable pH range of 8 +/- 1.
The results for physical stability and pH stability collectively support the 18month stability claim for the MTM for 18 months.
Performance testing
Limit of Detection Study
LoD testing was conducted to determine the lowest concentration of SARS-CoV-2 that contains measurable nucleic acids that can be repeatedly recovered from the transport media with a greater than 95% accuracy. The LoD was determined with in both preliminary and confirmatory studies as described below.
- i. Preliminary LoD Study: A preliminary LoD study was conducted using a virus stock of SARS-CoV-2 (GenBank MT126808.1, Stock: 2.70E+07 PFU/mL, initially diluted to 2.70E+06 PFU/mL, then 10-fold serially diluted) and three pooled negative clinical nasal samples in a 1:1 ratio (75 uL each) resulting in final sample SARS-CoV-2 concentrations of 1.35E+05, 1.35E+04, 1.35E+03, 1.35E+02 and 1.35E+01 PFU/mL.
Approximately 100 uL of each concentration was absorbed onto rayon swabs (Copan, CLASSIQSwabs) in triplicate to obtain virus concentrations of 1.35E+04. 1.35E+03, 1.35E+02, 1.35E+01 and 1.35 PFU. The swab was used to transfer each concentration of the virus and matrix into each lot of MTM at 15℃ and 35℃, respectively, prior to RNA extraction. SARS-CoV-2 RNA was extracted using MagMAX Viral/Pathogen Nucleic Acid Isolation Kit. Detection of SARS-CoV-2 RNA was conducted using the TaqPath COVID-19 Combo Kit (EUA200010) with the Applied Biosystems 7500 instrument. All procedures for nucleic acid extraction and amplification were performed following the manufacturer's instructions. The TagPath COVID-19 Combo Kit result interpretation per the manufacturer's instructions are summarized in Table 3 below.
Table 3: TagPath COVID-19 Combo Kit Result Interpretation. ALB LUZ Ltda.
8
| TaqPath COVID-19 Combo Kit Targets | Result | ||
|---|---|---|---|
| ORF1ab | N gene | S gene | |
| Two or more SARS-CoV-2 targets with Ct≤37 | Positive | ||
| Only one SARS-CoV-2 targets with Ct≤37 | Inconclusive | ||
| Ct>37 | Ct>37 | Ct>37 | Negative |
Results for preliminary LoD are summarized in Table 4.
| Table 4: Summary of Preliminary LoD Results for MTM at 15°C and 35°C. | |
|---|---|
| -- | ----------------------------------------------------------------------- |
| Lot | Temp (°C) | SARS-CoV-2 (PFU) | Replicate Number | Positive Number | ORF1ab | N gene | S gene |
|---|---|---|---|---|---|---|---|
| 880124MTM | 15 | 1.35E+03 | 3 | 3 | 32.90±1.18 | 34.05±0.80 | 32.22±0.88 |
| 1.35E+02 | 3 | 2 | 34.13±1.07 | 34.95±0.63 | 34.61±2.60 | ||
| 1.35E+01 | 3 | 1 | 36.08±0.52 | 37.41±1.69 | Undetermined | ||
| 1.35 | 3 | 3 | 34.85±0.62 | 35.16±0.52 | Undetermined | ||
| 880124MTM | 35 | 1.35E+03 | 3 | 3 | 34.89±1.69 | 35.91±1.21 | Undetermined |
| 1.35E+02 | 3 | 0 | 36.46±0.31 | Undetermined | Undetermined | ||
| 1.35E+01 | 3 | 0 | 37.85±0.23 | Undetermined | Undetermined | ||
| 1.35 | 3 | 0 | Undetermined | 34.62±0 | Undetermined | ||
| 112311150523MTM | 15 | 1.35E+03 | 3 | 3 | 31.53±1.02 | 33.10±0.78 | 31.37±1.18 |
| 1.35E+02 | 3 | 0 | 36.28±0.77 | 39.14±0.32 | Undetermined | ||
| 1.35E+01 | 3 | 0 | 37.56±0.60 | Undetermined | Undetermined | ||
| 1.35 | 3 | 3 | 34.50±0.48 | 35.69±0.90 | Undetermined | ||
| 112311150523MTM | 35 | 1.35E+03 | 3 | 2 | 33.98±1.30 | 36.62±3.01 | Undetermined |
| 1.35E+02 | 3 | 1 | 37.15±1.06 | 35.21±0 | Undetermined | ||
| 1.35E+01 | 3 | 0 | 39.96±0.49 | Undetermined | Undetermined | ||
| 1.35 | 3 | 0 | Undetermined | Undetermined | Undetermined | ||
| 02102022MTM | 15 | 1.35E+03 | 3 | 3 | 32.37±0.26 | 33.81±0.18 | 32.43±0.80 |
| 1.35E+02 | 3 | 3 | 34.14±0.63 | 35.46±1.02 | 34.55±0.89 | ||
| 1.35E+01 | 3 | 1 | 36.34±0.21 | 36.47±0 | Undetermined | ||
| 1.35 | 3 | 1 | 36.69±0.53 | 37.54±0.97 | Undetermined | ||
| 02102022MTM | 35 | 1.35E+03 | 3 | 2 | 34.36±0.66 | 35.46±1.45 | Undetermined |
| 1.35E+02 | 3 | 0 | 36.41±1.29 | 39.89±0 | Undetermined | ||
| 1.35E+01 | 3 | 0 | Undetermined | Undetermined | Undetermined | ||
| 1.35 | 3 | 0 | Undetermined | Undetermined | Undetermined |
The preliminary LoD at SARS-CoV-2 concentration 1.35E+04 PFU the results were 3/3 for all targets, data not shown. The concentration of 1.35E+03 PFU was determined to be the preliminary LoD for MTM at both 15°C and 35°C.
- ii. Confirmatory LoD: The confirmatory study was determined with 20 replicates for SARS-CoV-2 at concentrations of 1.35E+04, 1.35E+03 and 1.35E+02 PFU. Each replicate was inoculated into each lot of MTM tubes and were tested as previously described in the preliminary LoD study above. At a concentration of 1.35E+04 PFU the results were 20/20 for all targets, data not shown. Results for confirmatory LoD of MTM at 1.35E+03 and 1.35E+02 PFU are summarized in Table 5 below.
Table 5: Summary of Confirmatory LoD Results for MTM at 15℃ and 35℃.
| Lot | Temp | SARS-CoV-2 | Mean ± SD (Ct) | ||
|---|---|---|---|---|---|
ALB LUZ Ltda.
9
| | (°C) | (PFU) | Replicate
Number | Positive
Number | ORF1ab | N gene | S gene |
|-----------------|------|----------|---------------------|--------------------|------------|------------|------------|
| 880124MTM | 15 | 1.35E+03 | 20 | 20 | 30.70±1.44 | 31.10±1.46 | 29.92±0.78 |
| | 15 | 1.35E+02 | 20 | 11 | 35.55±1.34 | 37.01±1.73 | 35.10±0.74 |
| | 35 | 1.35E+03 | 20 | 20 | 30.22±0.53 | 30.40±0.65 | 29.55±0.57 |
| | 35 | 1.35E+02 | 20 | 1 | 37.61±1.13 | 36.80±1.16 | 37.25±0.66 |
| 112311150523MTM | 15 | 1.35E+03 | 20 | 19 | 29.78±0.52 | 30.04±0.62 | 29.54±0.57 |
| | 15 | 1.35E+02 | 20 | 15 | 35.48±0.97 | 36.34±1.71 | 35.50±0.91 |
| | 35 | 1.35E+03 | 20 | 20 | 30.39±0.71 | 30.15±0.74 | 29.70±0.53 |
| | 35 | 1.35E+02 | 20 | 14 | 35.56±1.19 | 35.37±0.81 | 34.73±1.90 |
| 02102022MTM | 15 | 1.35E+03 | 20 | 20 | 30.31±0.50 | 26.32±1.18 | 29.50±0.45 |
| | 15 | 1.35E+02 | 20 | 19 | 35.27±0.90 | 35.90±1.13 | 35.15±0.70 |
| | 35 | 1.35E+03 | 20 | 20 | 29.72±0.67 | 29.88±0.77 | 29.06±0.58 |
| | 35 | 1.35E+02 | 20 | 12 | 35.66±0.97 | 36.66±1.41 | 35.84±1.71 |
Based on the results, the confirmatory LoD for MTM is 1.35E+03 PFU.
Viral Nucleic Acid Stability Study
The SARS-CoV-2 virus stock (diluted to 6.00E+04 PFU/mL) were combined with pooled negative clinical nasal matrix in a 1:1 ratio (75 µL each) resulting in a final concentration of 3.00E+04 PFU. Approximately 100 µL of this mixture was absorbed onto rayon swabs in triplicate at a final virus concentration of 3.00E+03 PFU. Each swab was transferred into three MTM tubes of each lot and incubated at 15°C or 35°C for the following time points: 0, 7, 14 and 21 days post-inoculation. At the end of each time point, SARS-CoV-2 RNA was extracted using MagMAX Viral/Pathogen Nucleic Acid Isolation Kit, analyzed using TaqPath COVID-19 Combo Kit and Applied Biosystems 7500 instrument. All procedures for nucleic acid extraction and amplification were performed following the manufacturer's instructions. The results of the viral nucleic acid stability study summarized in Table 6 below.
| 15°C | 35°C | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Lot | Days | ORF1ab | N gene | S gene | ORF1ab | N gene | S gene | ||||||
| Mean | |||||||||||||
| Ct | ΔCt | Mean | |||||||||||
| Ct | ΔCt | Mean | |||||||||||
| Ct | ΔCt | Mean | |||||||||||
| Ct | ΔCt | Mean | |||||||||||
| Ct | ΔCt | Mean | |||||||||||
| Ct | ΔCt | ||||||||||||
| 880124MTM | 0 | 25.89 | 0 | 30.28 | 0 | 26.26 | 0 | 25.94 | 0 | 27.62 | 0 | 26.50 | 0 |
| 7 | 25.41 | 0.48 | 25.87 | 4.41 | 26.00 | 0.26 | 25.50 | 0.44 | 25.33 | 2.29 | 26.22 | 0.28 | |
| 14 | 25.45 | 0.44 | 25.57 | 4.71 | 26.35 | -0.09 | 25.78 | 0.16 | 25.62 | 2.00 | 26.45 | 0.04 | |
| 21 | 26.75 | -0.86 | 26.62 | 3.66 | 27.94 | -1.68 | 27.02 | -1.08 | 26.42 | 1.20 | 28.47 | -1.98 | |
| 112311150523MTM | 0 | 25.62 | 0 | 31.40 | 0 | 26.14 | 0 | 26.53 | 0 | 27.64 | 0 | 27.16 | 0 |
| 7 | 24.67 | 0.95 | 25.26 | 6.14 | 25.25 | 0.89 | 25.80 | 0.73 | 25.75 | 1.89 | 26.55 | 0.61 | |
| 14 | 24.96 | 0.66 | 25.10 | 6.30 | 25.71 | 0.43 | 27.16 | -0.63 | 26.14 | 1.50 | 27.09 | 0.07 | |
| 21 | 26.39 | -0.77 | 26.21 | 5.19 | 27.65 | -1.51 | 27.71 | -1.18 | 27.22 | 0.42 | 28.64 | -1.48 | |
| 02102022MTM | 0 | 25.34 | 0 | 27.71 | 0 | 25.90 | 0 | 26.46 | 0 | 27.19 | 0 | 27.25 | 0 |
| 7 | 25.58 | -0.24 | 25.83 | 1.88 | 26.36 | -0.46 | 24.50 | 1.96 | 24.48 | 2.71 | 25.25 | 2.00 | |
| 14 | 24.75 | 0.59 | 24.75 | 2.96 | 25.54 | 0.36 | 26.46 | 0.00 | 26.17 | 1.02 | 27.07 | 0.18 | |
| 21 | 26.03 | -0.69 | 25.88 | 1.83 | 26.94 | -1.04 | 27.00 | -0.54 | 26.33 | 0.86 | 28.30 | -1.05 | |
| ΔCt calculation (Mean Ct Day 0 minus Mean Ct Day 7, 14 and 21) |
Table 6: Summary of SARS-CoV-2 Viral Nucleic Acid Stability Results.
10
The MTM provided positive detection for all samples tested with Ct variation (ACt) less than ±3 Ct values for at least two of the three viral targets (ORF1ab, N gene and S gene) at time points 7, 14 and 21 days post-inoculation comparing to time point 0 for both 15°C and 35°C.
Based on these study results. MTM is able to provide stability to the SARS-CoV-2 viral nucleic acid (i.e., RNA) for 21 days at both 15 and 35°C.
Viral Inactivation Study
A viral inactivation study was conducted to test the ability of MTM to inactivate SARS-CoV-2 virus.
- i. Cytotoxicity: A volume of 30 µL of each lot of MTM was transferred to a 24-well microplate containing 270 µL of Dulbecco's Modified Eagle Medium with 10% fetal bovine serum cell culture media (DMEM with 10% FBS) and serially diluted (10-fold) to obtain dilutions of 1:10E+01 to 1:10E+08 in triplicate (i.e., three tubes per lot of MTM). Next, 300 µL of each dilution was added onto confluent Vero cells (ATCC, Cat: CCL-81) and incubated at 37°C at 5% CO2 for 48 hours. Cytotoxicity was determined visually using an inverted microscope looking for Cytopathic Effect (CPE). Results of the cytotoxicity study are summarized in Table 7 below.
| Lots* | Temp
(°C) | MTM
Dilution | Replicate
(MTM
tubes) | Cytotoxicity
(CPE) |
|-----------------------------------------------------------------------|--------------|-----------------|-----------------------------|-----------------------|
| 880124MTM
112311150523MTM
02102022MTM | 15 | 1:10E+01 | 3 | Cytotoxic |
| | | 1:10E+02 | 3 | |
| | | 1:10E+03 | 3 | Non-cytotoxic |
| | 35 | 1:10E+01 | 3 | Cytotoxic |
| | | 1:10E+02 | 3 | |
| | | 1:10E+03 | 3 | Non-cytotoxic |
| *Each MTM lot was tested individually and obtained identical results. | | | | |
| Table 7: Summarized of Cytotoxicity Study Results of MTM. |
|---|
The lowest dilution to indicate normal cell growth (i.e., no cytotoxicity) was determined to be the 1:10E+03 dilution in all lots at 15°C and 35°C of temperature storage. No cytotoxicity was observed for any of the dilutions from 1:10E+04 to 1:10E+08, data not shown.
- ii. Viral Inactivation: A volume of 75 µL of SARS-CoV-2 virus stock was mixed with 75 uL of pooled clinical negative nasal matrix in a 1:1 ratio to obtain a virus concentration of 1.35E+07 PFU/mL. Approximately 100 µL of this mixture was absorbed onto a rayon swab at a virus concentration of 1.35E+06 PFU and transferred into three tubes of each MTM lot number stored at 15°C and 35°C at time pointes of 0, 5 and 15-minutes post inoculation.
11
At the end of each time point, 30 uL of each sample was added into 270 uL of DMEM with 10% FBS cell culture media and serially diluted (10-fold) to 1:10E+01 to 1:10E+08 in triplicate (i.e., three tubes per lot of MTM). Next, 300 uL of each dilution was added onto confluent Vero cells and incubated at 37°C with 5% CO2 for virus absorption for one hour. Semisolid media containing DMEM with 10% FBS, 1% carboxymethylcellulose, and 1% penicillin/streptomycin antibiotics were added to each well and incubated at 37°C with 5% CO2 for up to 6 days. After the incubation period, the microplate wells containing the Vero cells were fixed with 10% paraformaldehyde, washed and stained with 1% crystal violet. Plaque-forming units (PFUs) were counted visually.
No PFUs were obtained after the exposure times of 0. 5 and 15 minutes for all MTM lot numbers at 15℃ and 35℃. All the results appear to be acceptable and support SARS-CoV-2 inactivation at 5 minutes exposure with MTM at 15℃ and 35°C.
Non-Clinical Performance Data
Non-clinical data submitted, referenced, or relied upon to demonstrate substantial equivalence included:
- CLSI M40-A2{2014) Quality Control of Microbiological Transport . Systems; Approved Standard Second Edition.
- ASTM O4169-16 Standard Practice for Performance Testing of . Shipping Containers and Systems
- USP-NF M98810 01 01 Sterility Tests
- . ISO 13408-1:2015 Aseptic processing of health care products -Part 1: General requirements
- ISO/CO 10993-7: 2008 Biological evaluation of medical devices Part ● 7: Ethylene oxide sterilization residuals
- ISO 11135:2014/Amd 1:2018 Sterilization of health-care products ● - Ethylene oxide - Requirements for the development, validation, and routine control of a sterilization process for medical devices – Amendment 1: Revision of Annex F. Single batch release.
Clinical performance Data
No clinical data were included in this submission.
Conclusion
The documentation submitted in this premarket notification demonstrates that the subject device K233324 has comparable features and performance and is substantially equivalent to the predicate device.