|
|
| (107 intermediate revisions by the same user not shown) |
| Line 1: |
Line 1: |
| [[File:Test PCR dépistage SARS-CoV-2 prélèvement nasal Strasbourg 21 août 2020.jpg|right|thumb|400px|SARS-CoV-2 PCR screening test by nasal swab in Strasbourg on August 21, 2020.]]In the previous chapter, the most common testing methodologies for [[COVID-19]] and other [[Coronavirus|coronaviruses]] were discussed in detail. The prevailing method (often called the "gold standard") among them all is real-time reverse-transcription [[polymerase chain reaction]] (rRT-PCR) assays for testing. Broadly speaking, PCR is useful in pharmaceutical, biotechnology, and genetic engineering endeavors, as well as clinical diagnostics. As such, labs in those industries that already have PCR infrastructure in place have a theoretical step-up over labs that do not.
| | {{Saved book |
| | |title=Introduction to Quality and Quality Management Systems |
| | |subtitle= |
| | |cover-image=Time-Quality-Money.png |
| | |cover-color=#fffccc |
| | | setting-papersize = A4 |
| | | setting-showtoc = 1 |
| | | setting-columns = 1 |
| | }} |
|
| |
|
| PCR technology has advanced to the point where it is more efficient and user-friendly than prior, yet "the high cost of the instruments, servicing contracts, and reagents pose major challenges for the market, especially to the price-sensitive academics."<ref name="MWPoly20">{{cite web |url=https://www.marketwatch.com/press-release/polymerase-chain-reaction-market-sector-analysis-report-regional-outlook-competitive-share-forecast---2023-2020-06-23 |archiveurl=https://web.archive.org/web/20200809215548/https://www.marketwatch.com/press-release/polymerase-chain-reaction-market-sector-analysis-report-regional-outlook-competitive-share-forecast---2023-2020-06-23 |title=Polymerase Chain Reaction Market Sector Analysis Report, Regional Outlook & Competitive Share & Forecast - 2023 |author=Kenneth Research |work=MarketWatch |date=23 June 2020 |archivedate=09 August 2020 |accessdate=08 September 2021}}</ref> Writing about the thirty-fifth anniversary of PCR in 2018, science writer Alan Dove not only highlighted these cost issues but also the size and energy requirements for running the equipment. "As a result, one of the defining techniques of modern molecular biology has remained stubbornly inaccessible to educators and unusable in many remote locations."<ref name="DovePCR18">{{cite journal |title=PCR: Thirty-five years and counting |journal=Science |author=Dove, A. |volume=360 |issue=6389 |pages=670–672 |year=2018 |doi=10.1126/science.360.6389.673-c}}</ref> Various efforts have been made over the years to bring costs down by modifying how heating and temperature control are performed<ref name="WongARapid15">{{cite journal |title=A Rapid and Low-Cost PCR Thermal Cycler for Low Resource Settings |journal=PLoS One |author=Wong, G.; Wong, I. Chan, K. et al. |volume=10 |issue=7 |at=e0131701 |year=2015 |doi=10.1371/journal.pone.0131701}}</ref><ref name="KuznetsovDIYbio15">{{cite journal |title=DIYbio Things: Open Source Biology Tools as Platforms for Hybrid Knowledge Production and Scientific Participation |journal=Proceedings of the 33rd Annual ACM Conference on Human Factors in Computing Systems |author=Kuznetsov, S.; Doonan, C.; Wilson, N. et al. |pages=4065–68 |year=2015 |doi=10.1145/2702123.2702235}}</ref><ref name="NortonPhila16">{{cite web |url=https://www.bizjournals.com/philadelphia/news/2016/05/11/government-contract-biomeme-hiring-med-tech.html |title=Phila. med tech startup working on multimillion dollar government contract |author=Norton, D. |work=Philadelphia Business Journal |date=11 May 2016 |accessdate=06 August 2020}}</ref><ref name="AnLow20">{{cite journal |title=Low-Cost Battery-Powered and User-Friendly Real-Time Quantitative PCR System for the Detection of Multigene |journal=Micromachines |author=An, J.; Jiang, Y.; Shi, B. et al. |volume=11 |at=435 |year=2020 |doi=10.3390/mi11040435}}</ref>, but many of those system aren't typically optimal during a pandemic when turnaround time is critical.
| | ==''Introduction to Quality and Quality Management Systems''== |
| | {{ombox |
| | | type = content |
| | | style = width: 500px; |
| | | text = This book should not be considered complete until this message box has been removed. This is a work in progress. |
| | }} |
| | The goal of this short volume is to act as an introduction to the quality management system. It collects several articles related to quality, quality management, and associated systems. |
|
| |
|
| Amidst the pandemic, additional challenges also exist to those wanting to conduct PCR testing for COVID-19 and other viruses. As was discussed at the end of the previous chapter, supplies of reagents and consumables are not particularly robust mid-pandemic, with various shortages being reported off and on since the start of the pandemic.<ref name="HerperShortage20">{{cite web |url=https://www.statnews.com/2020/03/10/shortage-crucial-chemicals-us-coronavirus-testing/ |title=Shortage of crucial chemicals creates new obstacle to U.S. coronavirus testing |work=STAT |author=Herper, M.; Branswell, H. |date=10 March 2020 |accessdate=10 April 2020}}</ref><ref name="HaleQiagen20">{{cite web |url=https://www.fiercebiotech.com/medtech/qiagen-aims-to-more-than-quadruple-its-covid-19-reagent-production-6-weeks |title=Qiagen aims to more than quadruple its COVID-19 reagent production in 6 weeks |work=Fierce Biotech |author=Hale, C. |date=18 March 2020 |accessdate=10 April 2020}}</ref><ref name="MehtaMystery20">{{cite web |url=https://www.chemistryworld.com/news/mystery-surrounds-uk-claim-of-covid-19-test-reagent-shortage/4011457.article |title=Mystery surrounds UK claim of Covid-19 test reagent ‘shortage’ |work=Chemistry World |author=Mehta, A. |date=03 April 2020 |accessdate=07 September 2021}}</ref><ref name="RocheIrish20">{{cite web |url=https://www.irishtimes.com/news/science/irish-scientists-develop-reagent-in-effort-to-ease-covid-19-testing-delays-1.4223897 |title=Irish scientists develop reagent in effort to ease Covid-19 testing delays |work=The Irish Times |author=Roche, B. |date=08 April 2020 |accessdate=10 April 2020}}</ref><ref name="PadmaEfforts20">{{cite web |url=https://www.chemistryworld.com/news/efforts-to-combat-covid-19-in-india-hit-by-imported-reagent-shortages/4011718.article#/ |title=Efforts to combat Covid-19 in India hit by imported reagent shortages |author=Padma, T.V. |work=Chemistry World |date=13 May 2020 |accessdate=19 May 2020}}</ref><ref name="DavidSurvey20">{{cite web |url=https://abcnews.go.com/Health/survey-shows-resources-covid-19-diagnostic-testing-limited/story?id=71341885 |title=Survey shows resources for COVID-19 diagnostic testing still limited months later |author=David, E.; Farber, S.E. |work=ABC News |date=20 June 2020 |accessdate=08 July 2020}}</ref><ref name="JohnsonNCLabs20">{{cite web |url=https://patch.com/north-carolina/charlotte/nc-labs-facing-shortages-covid-19-testing-chemicals |title=NC Labs Facing Shortages In COVID-19 Testing Chemicals |author=Johnson, K. |work=Patch |date=02 July 2020 |accessdate=08 July 2020}}</ref><ref name="MervoshItsLike20">{{cite web |url=https://www.nytimes.com/2020/08/04/us/virus-testing-delays.html |title=‘It’s Like Having No Testing’: Coronavirus Test Results Are Still Delayed |author=Mervosh, S.; Fernandez, M. |work=The New York Times |date=04 August 2020 |accessdate=05 August 2020}}</ref><ref name="CourageCovid20">{{cite web |url=https://www.vox.com/2020/7/31/21336212/covid-19-test-results-delays |title=Should we be testing fewer people to stop the spread of Covid-19? |author=Courage, K.H. |work=Vox |date=31 July 2020 |accessdate=05 August 2020}}</ref><ref name="ASMSupply20">{{cite web |url=https://asm.org/Articles/2020/September/Clinical-Microbiology-Supply-Shortage-Collecti-1 |title=Supply Shortages Impacting COVID-19 and Non-COVID Testing |author=American Society for Microbiology |publisher=American Society for Microbiology |date=09 November 2020 |accessdate=18 November 2020}}</ref><ref name="AbbottCovid20">{{cite web |url=https://www.wsj.com/articles/covid-19-testing-saps-supplies-needed-for-other-medical-tests-11604926800 |title=Covid-19 Testing Saps Supplies Needed for Other Medical Tests |author=Abbott, B.; Krouse, S. |work=The Wall Street Journal |date=09 November 2020 |accessdate=18 November 2020}}</ref><ref name="WilliamsSupply21">{{cite web |url=https://www.the-scientist.com/news-opinion/supply-shortages-hit-life-science-labs-hard-68695 |title=Supply Shortages Hit Life Science Labs Hard |author=Williams, S. |work=The Scientist |date=21 April 2021 |accessdate=07 September 2021}}</ref> Some of these shortages have gradually worked themselves out over time, but they highlight the need for other varying methods that don't necessarily depend on the same reagents and consumables that are in short supply.
| | ;1. What is quality? |
| | :''Key terms'' |
| | :[[Quality (business)|Quality]] |
| | :[[Quality assurance]] |
| | :[[Quality control]] |
| | :''The rest'' |
| | :[[Data quality]] |
| | :[[Information quality]] |
| | :[[Nonconformity (quality)|Nonconformity]] |
| | :[[Service quality]] |
| | ;2. Processes and improvement |
| | :[[Business process]] |
| | :[[Process capability]] |
| | :[[Risk management]] |
| | :[[Workflow]] |
| | ;3. Mechanisms for quality |
| | :[[Acceptance testing]] |
| | :[[Conformance testing]] |
| | :[[Clinical quality management system]] |
| | :[[Continual improvement process]] |
| | :[[Corrective and preventive action]] |
| | :[[Good manufacturing practice]] |
| | :[[Malcolm Baldrige National Quality Improvement Act of 1987]] |
| | :[[Quality management]] |
| | :[[Quality management system]] |
| | :[[Total quality management]] |
| | ;4. Quality standards |
| | :[[ISO 9000]] |
| | :[[ISO 13485]] |
| | :[[ISO 14000|ISO 14001]] |
| | :[[ISO 15189]] |
| | :[[ISO/IEC 17025]] |
| | :[[ISO/TS 16949]] |
| | ;5. Quality in software |
| | :[[Software quality]] |
| | :[[Software quality assurance]] |
| | :[[Software quality management]] |
|
| |
|
| For those labs wishing to adopt PCR testing of viruses—particularly COVID-19—into their workflow while providing reasonable turnaround times, all is not lost. However, careful planning is required. For example, you'll want to keep in mind that some PCR machines require vendor-specific reagents. If you're going to acquire a particular instrument, you'll want to do due diligence by verifying not only the supported reagents but also those reagents' overall availability (real and projected). You'll also want to consider factors such as anticipated workload (tests per day), what your workflow will look like, and how to balance overall investment with the need for reasonable turnaround times.
| | <!--Place all category tags here--> |
| | |
| An increasing body of research is being produced suggesting ways to improve turnaround times with PCR testing for COVID-19, with many research efforts focusing on cutting out RNA extraction steps entirely. Alcoba-Florez ''et al.'' [[Journal:Fast SARS-CoV-2 detection by RT-qPCR in preheated nasopharyngeal swab samples|propose]] direct heating of the sample-containing nasopharyngeal swab at 70 °C for 10 minutes in place of RNA extraction.<ref name="Alcoba-FlorezFast20">{{cite journal |title=Fast SARS-CoV-2 detection by RT-qPCR in preheated nasopharyngeal swab samples |journal=International Journal of Infectious Diseases |author=Alcoba-Florez, J.; González-Montelongo, R.; Íñigo-Campos, A.; García-Martínezde Artola, D.; Gil-Campesino, H.;<br />The Microbiology Technical Support Team; Ciuffreda, L.; Valenzuela-Fernández, A.; Flores, C. |volume=97 |pages=66–68 |year=2020 |doi=10.1016/j.ijid.2020.05.099}}</ref> Adams ''et al.'' have proposed an "adaptive PCR" method using a non-standard reagent mix that skips RNA extraction and can act "as a contingency for resource‐limited settings around the globe."<ref name="ShapiroStream20">{{cite web |url=https://news.vanderbilt.edu/2020/07/29/streamlined-diagnostic-approach-to-covid-19-can-avoid-potential-testing-logjam/ |title=Streamlined diagnostic approach to COVID-19 can avoid potential testing logjam |author=Shapiro, M. |work=Research News @ Vanderbilt |date=29 July 2020 |accessdate=06 August 2020}}</ref><ref name="AdamsCOVID20">{{cite journal |title=COVID‐19 diagnostics for resource‐limited settings: Evaluation of “unextracted” qRT‐PCR |journal=Journal of Medical Virology |author=Adams, N.M.; Leelawong, M.; Benton, A. et al. |year=2020 |doi=10.1002/jmv.26328}}</ref> Wee ''et al.'' skip RNA extraction and nucleic acid purification by using a single-tube homogeneous reaction method run on a lightweight, portable thermocycler.<ref name="MeharImproving20">{{cite web |url=https://www.techexplorist.com/improving-speed-gold-standard-covid-19-diagnostic-test/34069/ |title=Improving the speed of gold-standard COVID-19 diagnostic test |author=Mehar, P. |work=Tech Explorist |date=27 July 2020 |accessdate=06 August 2020}}</ref><ref name="WeeRapid20">{{cite journal |title=Rapid Direct Nucleic Acid Amplification Test without RNA Extraction for SARS-CoV-2 Using a Portable PCR Thermocycler |journal=Genes |author=Wee, S.K.; Sivalingam, S.P.; Yap, E.P.H. |volume=11 |issue=6 |at=664 |year=2020 |doi=10.3390/genes11060664}}</ref> Other innovations include tweaking reagents and enzymes to work with one step, skipping the reverse transcription step,<ref name="CSIRFaster20">{{cite web |url=https://www.engineeringnews.co.za/article/faster-local-covid-19-test-kits-could-be-ready-by-year-end-2020-07-30/ |title=Faster, local COVID-19 test kits could be ready by year-end |author=Council for Scientific and Industrial Research |work=Engineering News |publisher=Creamer Media |date=30 July 2020 |accessdate=07 August 2020}}</ref> and using saliva-based molecular testing that skips RNA extraction.<ref name="RanoaSaliva20">{{cite journal |title=Saliva-Based Molecular Testing for SARS-CoV-2 that Bypasses RNA Extraction |journal=bioRxiv |author=Ranoa, D.R.E.; Holland, R.L.; Alnaji, F.G. et al. |year=2020 |doi=10.1101/2020.06.18.159434}}</ref><ref name="ThomasFast20">{{cite web |url=https://www.news-medical.net/news/20200806/Fast-cheap-and-easy-COVID-19-test-from-Yale.aspx |title=Fast, cheap and easy COVID-19 test from Yale |author=Thomas, L. |work=News Medical - Life Sciences |date=06 August 2020 |accessdate=16 August 2020}}</ref>
| |
| | |
| '''Saliva as a specimen'''
| |
| | |
| The saliva molecular tests in particular are intriguing. Talk of the potential utility of using saliva as a specimen for COVID-19 was occurring as early as April 2020<ref name="XuSaliva20">{{cite journal |title=Saliva: Potential diagnostic value and transmission of 2019-nCoV |journal=International Journal of Oral Science |author=Xu, R.; Cui, B.; Duan, X. et al. |volume=12 |at=11 |year=2020 |doi=10.1038/s41368-020-0080-z}}</ref><ref name="GreenwoodSaliva20">{{cite web |url=https://news.yale.edu/2020/04/24/saliva-samples-preferable-deep-nasal-swabs-testing-covid-19 |title=Saliva samples preferable to deep nasal swabs for testing COVID-19 |author=Greenwood, M. |work=YaleNews |date=24 April 2020 |accessdate=01 May 2020}}</ref>, and the first saliva-based COVID-19 test, produced by Spectrum Solutions in cooperation with RUCDR Infinite Biologics Laboratory<ref name="SSFirst20">{{cite web |url=https://spectrumsolution.com/fda-authorized-covid-19-updates/ |title=First saliva collection device FDA EUA authorized for COVID-19 testing |publisher=Spectrum Solutions |date=2020 |accessdate=16 August 2020}}</ref> and Vault Health<ref name="VHVault20">{{cite web |url=https://www.prnewswire.com/news-releases/vault-health-launches-first-of-its-kind-saliva-based-fda-eua-approved-test-for-covid-19-301039633.html |title=Vault Health Launches First-of-its-Kind Saliva-based FDA EUA Approved Test for COVID-19 |author=Vault Health |work=PR Newswire |date=14 April 2020 |accessdate=01 May 2020}}</ref>, was given an FDA EUA in April 2020. On August 15, 2020, Yale School of Public Health was given an EUA for it SalivaDirect molecular test. Although still PCR-based (and a CLIA high-complexity test), SalivaDirect is being touted as a means to improve specimen collection safety, consume fewer reagents, prove compatible with high-throughput workflow, and cut overall turnaround time. Not only is saliva easier to collect and safer for healthcare staff, the test is essentially "open sourced," not requiring proprietary equipment from Yale, making the test more flexible by being validated to reliably function with a wider array of reagents and instruments.<ref name="GallagherFDA20">{{cite web |url=https://www.contagionlive.com/view/fda-grants-emergency-covid19-authorization-yale-open-source-method-saliva-testing |title=FDA Grants Emergency COVID-19 Authorization to Yale's Open Source Method of Saliva Testing |author=Gallagher, G.M. |work=ContagionLive |date=15 August 2020 |accessdate=16 August 2020}}</ref><ref name="ZillgittFDA20">{{cite web |url=https://www.usatoday.com/story/sports/nba/2020/08/15/fda-approves-covid-19-saliva-test-developed-yale-nba-nbpa-aid/5590452002/ |title=FDA approves COVID-19 saliva test developed at Yale in partnership with the NBA, NBPA |author=Zillgitt, J. |work=USA Today |date=15 August 2020 |accessdate=16 August 2020}}</ref> When compared to using a nasopharyngeal swab specimen using the ThermoFisher Scientific TaqPath COVID-19 combo kit, results were comparable 94.1% of the time.<ref name="ThomasFast20" /> While sensitivity and specificity may be slightly less comparable to other PCR options<ref name="WeisslederCOVID20">{{cite web |url=https://csb.mgh.harvard.edu/covid |title=COVID-19 Diagnostics in Context |author=Weissleder, R.; Lee, H.; Ko, J. et al. |publisher=Harvard Center for Systems Biology |date=15 August 2020 |accessdate=16 August 2020}}</ref>, the overall advantages during reagent shortages and a definitive need for broader testing likely outweigh the slightly lesser sensitivity and specificity. In November 2020, public health agencies in Arizona and Minnesota reportedly began running trials of free saliva-based molecular testing.<ref name="ParsonsPlaces20">{{cite web |url=https://www.azfamily.com/news/continuing_coverage/coronavirus_coverage/places-with-saliva-based-covid-testing-expecting-influx-of-people/article_76ac95c4-26b5-11eb-b34e-3728b1308927.html |title=Places with saliva-based COVID testing expecting influx of people |author=Parsons, J. |work=AZFamily |date=14 November 2020 |accessdate=19 November 2020}}</ref><ref name="MDoHState20">{{cite web |url=https://www.health.state.mn.us/news/pressrel/2020/covid102220.html |title=State launches pilot of COVID-19 test at home saliva program |author=Minnesota Department of Health |publisher=Minnesota Department of Health |date=22 October 2020}}</ref>
| |
| | |
| As the pandemic has progressed into 2021, saliva testing has become even more attractive, in particular for at-home over-the-counter testing.<ref name="PugleNininv21">{{cite web |url=https://www.healthline.com/health-news/noninvasive-saliva-tests-for-covid-19-as-effective-as-nose-throat-swabs |title=Noninvasive Saliva Tests for COVID-19 as Effective as Nose, Throat Swabs |author=Pugle, M. |work=Healthline |date=20 January 2021 |accessdate=08 September 2021}}</ref><ref name="KarkusDiff21">{{cite web |url=https://www.pharmacytimes.com/view/differences-between-saliva-covid-19-tests-nasal-swab-covid-19-tests |title=Differences Between Saliva COVID-19 Tests, Nasal Swab COVID-19 Tests |author=Karkus, T. |work=Pharmacy Times |date=05 April 2021 |accessdate=08 September 2021}}</ref> In August 2021, Spectrum Solutions received an EUA for its Spectrum Solutions SDNA-1000 saliva collection system, specifically designed "to avoid user collection errors" and eliminate "the requirement for any bio-sample temperature-controlled storage or transport,"<ref name="NSMedStaffSpect21">{{cite web |url=https://www.nsmedicaldevices.com/news/spectrum-solutions-covid-19-testing/ |title=Spectrum Solutions’ device gets FDA EUA for unsupervised saliva collection for Covid-19 testing |author=NS Medical Staff Writer |work=NS Medical Devices |date=18 August 2021 |accessdate=08 September 2021}}</ref> arguably upping the game for new saliva-based test kits going forward. Additionally, as variants of COVID-19 continue to crop up, additional saliva-based at-home tests are coming into development. For example, researchers at the Wyss Institute, the Massachusetts Institute of Technology, and Boston-area hospitals have been working on a laboratory-developed test called Minimally Instrumented SHERLOCK (miSHERLOCK) based on CRISPR (clustered regularly interspaced short palindromic repeats) technology. The researchers claim that the test, able to be used with typical off-the-shelf components, "works as well as the gold standard PCR tests and could cost as little as $3 per test."<ref name="HealthDayAtHome21">{{cite web |url=https://www.webmd.com/lung/news/20210807/at-home-saliva-test-can-spot-covid-variants#1 |title=At-Home Saliva Test Can Spot COVID Variants |author=HealthDay News |work=WebMD |date=06 August 2021 |accessdate=08 September 2021}}</ref><ref name="DePuigMinim21">{{cite journal |title=Minimally instrumented SHERLOCK (miSHERLOCK) for CRISPR-based point-of-care diagnosis of SARS-CoV-2 and emerging variants |journal=Science Advances |author=De Puig, H.; Lee, R.A.; Najjar, D. et al. |volume=7 |issue=32 |at=eabh2944 |year=2021 |doi=10.1126/sciadv.abh2944 |pmid=34362739 |pmc=PMC8346217}}</ref>
| |
| | |
| ==References==
| |
| {{Reflist|colwidth=30em}}
| |
