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PrimeStore MTM is intended for the stabilization, transportation and inactivation of infectious unprocessed nasal washes suspected of containing Influenza A virus RNA. PrimeStore MTM is also intended for the stabilization, transportation and inactivation of infectious unprocessed sputum samples suspected of containing Mycobacterium tuberculosis DNA from human samples.

Device Description

The PrimeStore MTM device consists of a storage tube with an O-ring and lip seal containing 1.5 mL of the stabilization solution. These components are intended to inactivate Influenza A and Mycoplasma tuberculosis, lyse cells, disrupt/lyse lipid membranes, denatures proteins, inactivates enzymes, and stabilize Influenza A RNA and M. tuberculosis DNA. The transport device is designed for storage of specimens between 36-77 °F (2-25 °C).

The media contains the following reagents:

o Guanidine thiocyanate
o TCEP
Sodium Citrate ●
N-Lauroylsarcosine sodium (NLS) ●
Antifoam A, TRIS ●
EDTA ●
Ethanol (molecular grade)
HCl ●
Nuclease-free water ●

AI/ML Overview

The PrimeStore MTM device is intended for the stabilization, transportation, and inactivation of infectious unprocessed nasal washes suspected of containing Influenza A virus RNA, and infectious unprocessed sputum samples suspected of containing Mycobacterium tuberculosis DNA. The acceptance criteria and the studies proving the device meets these criteria are detailed below.

1. Table of Acceptance Criteria and Reported Device Performance

Criteria Category	Specific Criteria	Reported Device Performance
Limit of Detection (LoD)	Mycobacterium Tuberculosis (MTB): - Recoverable concentration where at least 95% of replicates are within a 3 Ct range.	MTB: - At 10¹ CFU/mL, 25 of 25 replicates had recoverable concentrations, and all fell within the 3 Ct range. Average CT = 34.0, S.D. = 0.98. - At 10⁴ CFU/mL and 10² CFU/mL, all 25 replicates met the acceptance criteria.
	Influenza A (Flu A): - Recoverable concentration where at least 95% of replicates are within a 3 Ct range.	Flu A: - At 10² TCID50/mL, 25 of 25 replicates had recoverable concentrations; one replicate had a high Ct value outside the 3 Ct range, but the overall concentration still met the criterion. Average CT = 34.5, S.D. = 0.88.
Stability	MTB: - +/- 3.0 Ct from time zero for 36 days at 4°C and 27°C, without loss of detection signal.	MTB: - DNA from MTB in PrimeStore MTM showed a variation of 1.6 Ct or less over 36 days at both 4°C and 27°C. Positive samples not stored in PrimeStore MTM demonstrated degraded DNA as time and temperature increased.
	Flu A: - +/- 3.0 Ct from time zero for 29 days at 4°C and for 8 days at 27°C, without loss of detection signal.	Flu A: - RNA from Influenza A in PrimeStore MTM showed a variation of 2.7 Ct over 29 days at 4°C and a variation of 2.0 Ct over 8 days at 27°C. Positive samples not stored in PrimeStore MTM demonstrated degraded RNA as time and temperature increased.
Inactivation	MTB: - No growth in all samples after 42 days of incubation, requiring a specific sputum-to-PrimeStore MTM ratio and minimum exposure time.	MTB: - At 1.5 x 10⁶ CFU/mL, no growth was observed across all ratios (1:3, 1:2, 1:1) and all time points (1 to 180 minutes). - At 1.5 x 10⁸ CFU/mL, inactivation was successful (no growth) with a ratio of at least 1:3 sputum to PrimeStore MTM and a minimum of 60 minutes exposure time. Intermittent growth was observed at other ratios and shorter exposure times.
	Flu A: - Demonstrate rapid inactivation (e.g., log reduction) within specified timelines, while noting potential cytotoxicity of the media at high concentrations.	Flu A: - PrimeStore MTM showed cytotoxicity on MDCK cells when diluted 1:100 but not at 1:1,000. - Rapidly inactivated Influenza A virus with a >4.0 log reduction in concentration at 10 seconds. - Viral CPE could not be observed at < 3.0 logs due to cellular destruction by PrimeStore MTM. - Requires a ratio of at least 1:3 nasal to PrimeStore MTM and a minimum of 10 seconds exposure time to demonstrate inactivation.
Extraction/Amplification Compatibility	MTB: - Show similar Limit of Detection for MTB DNA in PrimeStore MTM compared to PBS control using various nucleic acid extraction and PCR amplification systems.	MTB: - For QIAamp, MagNA Pure 96, and NucliSENS easyMAG, the LoDs for MTB DNA in PrimeStore MTM were mostly similar to or better than the PBS control using an FDA cleared assay (except for QIAamp at lower concentrations). - The ABI 7500 and LightCycler 2.0 PCR platforms showed similar results, with variation within each instrument averaging within 1 Ct, and between instruments ranging from 1 to 1.7 Ct. The QIAamp extraction method increased the LoD by two logs compared to others.

2. Sample Size Used for the Test Set and Data Provenance

Mycobacterium Tuberculosis (LoD & Stability):
- LoD (preliminary): 7 concentrations tested, each in quadruplicate.
- LoD (confirmatory): 25 replicates at 10¹ CFU/mL.
- Stability: 25 replicates extracted at each time point (Day 0, 1, 8, 15, 22, 29, 36) for both 4°C and 27°C.
- Provenance: Spiked pooled sputum known to be negative for MTB. The M. tuberculosis strain used for LoD studies was HN878 (BEI Resources, Catalog No. NR-13647).
Influenza A (LoD & Stability):
- LoD (preliminary): Multiple concentrations, each in triplicate.
- LoD (confirmatory): 25 replicates at 10² TCID50/mL.
- Stability: 25 replicates extracted at each time point (Day 0, 1, 8, 15, 22, 29 for 4°C; Day 0, 1, 8 for 27°C).
- Provenance: Spiked pooled, clinically negative nasal washes. Influenza A strain used was A/Texas/78209/2008 (H3N2).
Mycobacterium Tuberculosis (Inactivation):
- Sample Source: Sputum samples not submitted for MTB investigation obtained from the diagnostic laboratory at the University of Pretoria (Pretoria, South Africa).
- Test Set: Good quality purulent sputum specimens (Bartlett test score of 2+) were split and spiked with MTB H37Rv strain (1.5 x 10⁶ and 1.5 x 10⁸ CFU/mL). Inoculated into PrimeStore MTM, incubated in triplicate for each time point (1, 5, 10, 30, 60, and 180 minutes) and ratio (1:3, 1:2, 1:1 sputum to PrimeStore MTM).
Influenza A (Inactivation):
- Test Set: Influenza/A/Wuhan/359/95 (10⁰ TCID50/ml) incubated with PrimeStore MTM for 10, 30, and 60 seconds.
- Provenance: Not specified as clinical or laboratory samples, but refers to "Influenza/A/Wuhan/359/95" which is a known laboratory strain.
Extraction/Amplification Compatibility:
- MTB: Sputum spiked with MTB at final concentrations ranging from 3 to 250,000 CFU/mL. For each extraction method, 20 samples were tested at various concentrations. For amplification comparison, three 10-fold concentrations (1 X 10, 1 X 10³, and 1 x 10⁴ CFU/mL) of MTB extracted from sputum stored in PrimeStore MTM were tested in duplicate on each instrument.
- Provenance: Spiked sputum samples.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not mention the use of human experts to establish ground truth. The ground truth for the analytical performance studies (LoD, stability, inactivation, compatibility) was established through laboratory-controlled spiking experiments using known concentrations of bacterial or viral strains into clinically negative matrices, followed by molecular detection methods (real-time PCR) or culture methods.

4. Adjudication Method for the Test Set

Not applicable. The studies are analytical performance studies based on objective measurements (Ct values, growth/no growth) and not subjective interpretation requiring adjudication among experts.

5. 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 transport medium for nucleic acids, not an AI-assisted diagnostic tool. Therefore, MRMC studies and assessment of AI assistance for human readers are not relevant.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done

Not applicable. This device is not an algorithm or a software-based diagnostic tool. It is a physical transport medium. The "standalone" performance here refers to the device's ability to preserve and inactivate without human intervention during the storage and transport phase, which is what the analytical studies (stability, inactivation) directly assess.

7. The Type of Ground Truth Used

The ground truth used in these analytical studies is primarily:

Known concentrations of specific microbial strains: For LoD and stability, quantified CFU/mL (for MTB) or TCID50/mL (for Influenza A) were spiked into relevant matrices.
Absence of target nucleic acid/organism: Clinically negative pooled sputum or nasal washes were used as matrices for spiking experiments, serving as negative controls.
Absence of microbial growth: For inactivation studies, the absence of growth after incubation in culture media (MGIT 960 system) served as the ground truth for successful inactivation.
Real-time PCR Ct values: These values serve as a quantitative measure of nucleic acid presence and concentration, forming the basis for assessing stability and LoD within predefined acceptance ranges.

8. The Sample Size for the Training Set

Not applicable. This device is a physical transport medium and does not involve machine learning or AI, and therefore does not utilize a "training set" in the context of algorithm development. The studies described are analytical validation studies for device performance.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no training set for this type of device.

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