Sample Collection & Primary focus on covid. Origin, structure, - - PowerPoint PPT Presentation
Sample Collection & Primary focus on covid. Origin, structure, transmissibility, incubation, mechanism of disease, public health policy in relation to spread. Maybe briefly on comparison to others like SARS, MERS, swine and bird flus, why
Primary focus on covid. Origin, structure, transmissibility, incubation, mechanism of disease, public health policy in relation to spread. Maybe briefly on comparison to others like SARS, MERS, swine and bird flus, why this time different, etc.
Susan E. Sharp, Ph.D. Scientific Director, Copan Diagnostics, Inc.
1
2
manufacturing.
collection.
recommendations by the FDA during the COVID19 epidemic.
3
General D Description
December to March
4
CoV
SARS – Sudden Acute Respiratory Syndrome
– SARS-CoV – atypical pneumonia high fever, chills,
malaise, mortality ~10%
– 2002 outbreak – believed that the virus
jumped species from bats to animals raised for food (civet cat; racoon dog) to man in China
– 8300 cases – 785 deaths
5
MERS – Middle Eastern Respiratory Syndrome (MERS-CoV)
Saudi Arabia in 2012
been documented.
MERS in the U.S.
– > May 2014, MERS was confirmed in the U.S. in 2 travelers
from Saudi Arabia
– > CDC recognizes the potential for MERS-CoV to spread &
cause more cases in the U.S. and globally
– > Information provided for travelers – > Health departments, hospitals, & clinicians prepared
6
pangolin
7
Sudden Acute Respiratory Syndrome SARS-CoV-2
The only known mammals to have large, protective keratin scales covering their skin. Sought after for ethnomedicine.
8
Origin: Wuhan China Open air “wet market” ?
9
(range ~6’).
week of symptoms then declines.
destabilizes the lipid bilayer of its envelope.
10
11
Average # of people that will get the infection from 1 infected person
If R0 < 1, each existing infection causes less than one new infection; the disease will decline and eventually die out. If R0 = 1, each existing infection causes one new infection; the disease will stay alive and stable, but there won’t be an outbreak
If R0 > 1, each existing infection causes more than one new infection; the disease will be transmitted between people, and there may be an
R0 only applies when everyone in a population is susceptible to the disease. This means:
No one has been vaccinated No one has had the disease before There’s no way to effectively control the spread of the disease
12
10 generations of infection
56 56
13
10 generations of infection
56 56
14
10 generations of infection
56 56
16
ibili lity (verified to be non-cytotoxic, non-irritating, and non-sensitizing) for limited contact.
mechanical p properties, flexibility, durability after sterilization including tensile testing, torsional testing, and flexural testing.
dequate collection o
f specime men from nasal, nasopharyngeal, oropharyngeal, etc. sites.
17
18
The ste steriliz lization tion process is validated by the manufacturer prior to distribution including the bioburden testing of final product. Packa kaging must address seal strength and packaging integrity for shipping. Swabs would be lab labele led appropriately for their intended use, including the site it is intended to sample [e.g. nasal, nasopharyngeal, etc.). Lab abeli ling w will in ill inclu lude:
Examples:
19
ISO 13485:2016 Medical devices -- Quality management system ISO 10993-1:2018 Biological evaluation of medical devices
20
Flocked swab Spun fiber swab
23
(vortexing)
24
(vortexing)
Samples collected and transferred into preservation medium:
Viral T al Tran ansp sport t Media ( ia (VT VTM o
UTM™): Viruses, Chlamydia, Mycoplasma, Ureaplasma
es: Routine bacteriology
iliz izatio tion M Media ia: General microbiology molecular testing
UTM™ Universal Transport Medium
FDA cleared collection and transport system suitable for collection, transport (48 hrs @ RT/4C), maintenance and long-term freeze storage of clinical specimens. An open platform that can be used for: Culture EIA DFA NAAT Paired with Flocked swabs = equivalent to nasal aspirates and nasal washes for the diagnosis of respiratory virus infections.
Liquid Based Collection and Transport System
for Microbiology Samples
Flocked swab + 1mL of Liquid Amies in a plastic, screw cap tube. Collection and transport device for aerobic, anaerobic, and fastidious bacteria for up to 48 hours.
Guanidine-thiocyanate based medium which stabilizes RNA and DNA
A Guanidine-thiocyanate based medium that stabilizes RNA and DNA of viruses, bacteria. Ensures preservation of RNA and DNA at room temperature for weeks or months (if frozen). Inactivates microbial viability allowing safe specimen handling.
FDA N A NOTE: : This transport media contains guanidine thiocyanate which produces a dangerous chemical reaction releasing cyanide gas when exposed to bleach.
WARNI NING NG: Do not use PrimeStore MTM with the Hologic Panther or Panther Fusion Systems due to a disinfecting step involving bleach that is specific to the platform.
transport media, it produces dangerous cyanide gas.
Guanidine-thiocyanate based medium which stabilizes RNA and DNA
30
submit an EAU to the FDA within 15 business days after their validation is complete and distribution/testing has started.
CDC a assay issued 1st EUA on 2/4/20:
materials were authorized by the FDA thereafter.
31
February 29 March 23 April 3 April 14 May 6 Overview Healthcare workers can take NP / OP swabs in facility CDC assay (2/4/20) Individuals can self- collect samples in facility with foam nasal swab All swabs can be stored in normal saline as alternative transport media Polyester swabs can be used for nasal collection with expanded supply Self-collected nasal swab using spun polyester in dry tube, with no cold chain for up to 3 days Components authorized by FDA Specimen collector HCW HCW, Self HCW, Self HCW, Self HCW, Self Specimen sites/swabs NP, OP (HCW only) NP, OP (HCW only) MT (Flocked), Nasal NP, OP (HCW only) MT (Flocked), Nasal NP, OP (HCW only) MT (Flocked), Nasal NP, OP (HCW only) MT (Flocked), Nasal Nasal swab materials Foam Foam Foam Polyester, Rayon Foam, Spun Polyester, Rayon Transport media VTM Added: 1st - liquid Amies 2nd - PBS VTM liquid Amies PBS VTM liquid Amies PBS Normal saline VTM liquid Amies PBS Normal saline NA media VTM liquid Amies PBS Normal saline NA media Dry Physical testing site Healthcare facility or drive-thru Healthcare facility or drive-thru Healthcare facility or drive-thru Healthcare facility or drive-thru Healthcare facility, drive-thru, Home Collection
Based on several 2020 investigators/studies
FDA believes that a flocked nasopharyngeal specimen is the preferred choice for swab-based SARS-CoV-2 testing. If a flocked nasopharyngeal specimen is not available, then any of the following are acceptable:
Swab education_Norman Sharples_051120
https://www.nejm.org/doi/full/10.1056/NEJMvcm2010260#full
32
33
(supported by The Gates Foundation)
Study Purpose Site of Collection Swab Type Transport Media Clinical Site Laboratory Study outcome
Everett Clinic #1 Evaluate self-collection, from alternative sites Nasopharyngeal Comparator VTM Everett Clinic/UHG Quest Diagnostics
healthcare worker
healthcare worker
healthcare worker Nasal Foam Mid-turbinate Flocked nylon Tongue dorsum Flocked nylon Stanford Evaluate self-collection, from nasal passage Oropharyngeal Comparator VTM Stanford Stanford Clinical Virology Lab
equivalent to OP
Nasal Foam Everett Clinic #2 Evaluate alternative polyester swab Nasal Foam VTM Everett Clinic/UHG Quantigen
with VTM (foam may be slightly more sensitive at very low viral concentration)
with saline (foam may be slightly more sensitive at very low viral concentration) Polyester Foam Saline Evaluate alternative transport media Polyester Quantigen # 1 Evaluate variable heat stability of virus on foam and polyester swab in saline and dry conditions Nasal Foam Dry N/A Quantigen
40C).
at 40C)
(12hr at 40C) Polyester Saline 32C 40C Foam-dry 80 hr 12 hr Polyester-dry 80 hr 12 hr Polyester-saline 56 hr 12 hr
96% 94% < 90%
34
Study Purpose Site of Collection Swab Type Transport Media Clinical Site Laboratory Study outcome Quest Evaluated stability of virus RNA in specimen transport media at various storage conditions NP/ OP / sputum/BAL with spiked sample various UTM M4 ESwab saline N/A Quest Diagnostics
transport media: Ct values were stable from -30oC to 25oC for 7-10 days 1
Seattle Evaluated dry swabs Mid- turbinate Flocked VTM Home collection kits UW
that dry swabs would support detection of SARS-CoV-2 without impacting sensitivity
Dry
1 https://jcm.asm.org/content/jcm/early/2020/04/23/JCM.00708-20.full.pdf
35
Example:
Self-collection of anterior nares specimen, at home or in community setting Spun polyester swab Swab placed in dry tube or in saline Sent to the lab in the mail RT stable for up to 3 days with dry swab (2 days in saline) Laboratory testing and results returned to the individual at home
, foam swab
36
(polyester nasal/saline)
37
38
(foam nasal/saline)
39
40
Collect an adequate specimen
transport
Collection and transport devices are essentia tial components of the preanalytical process of microbiology testing. These early steps in the preanalytical process are critic tical to production of clinically relevant information.
https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-testing-sars-cov-2#whatif
Primary focus on covid. Origin, structure, transmissibility, incubation, mechanism of disease, public health policy in relation to spread. Maybe briefly on comparison to others like SARS, MERS, swine and bird flus, why this time different, etc.
43