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| <blockquote>''We’ve never faced this before, where clinical labs needed to very quickly be able to ramp up a test so fast.''<ref name="TerryCRISPR20">{{cite web |url=https://www.biospace.com/article/crispr-discoverer-jennifer-doudna-launches-covid-19-test-lab/ |title=CRISPR Pioneer Jennifer Doudna Expects Automated COVID-19 Test Lab to Begin Testing Next Week |work=BioSpace |author=Terry, M. |date=30 March 2020 |accessdate=10 April 2020}}</ref><br /> <br />- Jennifer Doudna, Executive Director of the Innovative Genomics Institute, University of California, Berkeley</blockquote>
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| Though the dismantling and fund-cutting (proposed and real) of government programs designed to protect the populace from pandemics—as well as shortfalls in funding overall<ref name="SandsTheNeglect16">{{cite journal |title=The Neglected Dimension of Global Security — A Framework for Countering Infectious-Disease Crises |journal=The New England Journal of Medicine |author=Sands, P.; Mundaca-Shah, C.; Dzau, V.J. |volume=374 |issue=13 |pages=1281–87 |year=2016 |doi=10.1056/NEJMsr1600236 |pmid=26761419}}</ref>—have likely hobbled local, national, and global response to COVID-19<ref name="MorrisTrump20">{{cite web |url=https://fortune.com/2020/02/26/coronavirus-covid-19-cdc-budget-cuts-us-trump/ |title=Trump administration budget cuts could become a major problem as coronavirus spreads |work=Fortune |author=Morris, C. |date=26 February 2020 |accessdate=10 April 2020}}</ref><ref name="SpecterTheCorona20">{{cite web |url=https://www.newyorker.com/news/daily-comment/coronavirus-and-the-gutting-of-americas-public-health-system |title=The Coronavirus and the Gutting of America’s Public-Health System |work=The New Yorker |author=Specter, M. |date=17 March 2020 |accessdate=10 April 2020}}</ref><ref name="RoosCongress07">{{cite web |url=https://www.cidrap.umn.edu/news-perspective/2007/05/congress-cut-pandemic-funds-passing-spending-bill |title=Congress cut pandemic funds before passing spending bill |work=CIDRAP - News & Perspective |author=Roos, R. |date=25 May 2007 |accessdate=10 April 2020}}</ref><ref name="SchnirringCongress07">{{cite web |url=https://www.cidrap.umn.edu/news-perspective/2007/12/congress-slashes-pandemic-preparedness-funding |title=Congress slashes pandemic preparedness funding |work=CIDRAP - News & Perspective |author=Schnirring, L. |date=20 December 2007 |accessdate=10 April 2020}}</ref>, it should be recognized that this pandemic may arguably represent a once-in-a-century type of event.<ref name="GatesRespond20">{{cite journal |title=Responding to Covid-19 — A Once-in-a-Century Pandemic? |journal=The New England Journal of Medicine |author=Gates, B. |year=2020 |doi=10.1056/NEJMp2003762 |pmid=32109012}}</ref><ref name="ShontellMelinda20">{{cite web |url=https://www.businessinsider.com/melinda-gates-coronavirus-interview-vaccine-timeline-2020-4 |title=Melinda Gates: This is not a once-in-a-century pandemic. 'We will absolutely have more of these.' The billionaire philanthropist predicts a timeline for going back to normal |work=Business Insider |author=Shontell, A. |date=10 April 2020 |accessdate=10 April 2020}}</ref> That said, even the most well-prepared governments would still face challenges in quickly learning about, controlling, and developing therapies for a novel disease agent. Shortages in supplies, workers, funding, and other resources are inevitably caused with a pandemic as people across all types of infrastructure fall ill.<ref name="SandsTheNeglect16" /><ref name="MadhavPandemics17">{{cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK525302/ |chapter=Chapter 17: Pandemics: Risks, Impacts, and Mitigation |title=Disease Control Priorities: Improving Health and Reducing Poverty |edition=3rd |author=Madhav, N.; Oppenheim, B.; Gallivan, M. et al. |editor=Jamison, D.T.; Gelband, H.; Horton, S. et al. |publisher=The World Bank |year=2017 |isbn=9781464805288}}</ref> This requires the additional human elements of adaptability, drive, and shared knowledge to find new and alternative solutions to fighting the challenges inherent to fighting against a novel disease.
| | ==''Introduction to Quality and Quality Management Systems''== |
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| | 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. |
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| See for example a non-peer-reviewed paper published on ''bioRxiv'' in early April 2020, where Schmid-Burgk ''et al.'' pointed out that though RT-PCR methods are the most common for currently testing for SARS-CoV-2, "global capacity for testing using these approaches, however, has been limited by a combination of access and supply issues for reagents and instruments." They proposed "a novel protocol that would allow for population-scale testing using massively parallel RT-LAMP by employing sample-specific barcodes." They claimed that a single heating step, pooled processing, and parallel sequencing with computational analysis would allow for the testing and tacking of "tens of millions of samples." Though the protocol was not validated with clinical samples, and concerns about sensitivity levels of RT-LAMP (an isothermal nucleic acid amplification technique that allows for RNA amplification) have been raised, the authors' work exemplifies the immediacy and ingenuity that has gone into finding workable solutions to a once-a-century problem.<ref name="Schmid-BurgkLAMP20">{{cite journal |title=LAMP-Seq: Population-Scale COVID-19 Diagnostics Using Combinatorial Barcoding |journal=bioRxiv |author=Schmid-Burgk, J.L.; Li, D.; Feldman, D. et al. |year=2020 |doi=10.1101/2020.04.06.025635}}</ref>
| | ;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]] |
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| Another example of ingenuity in the face of difficult circumstances can be found at the University of California, Berkeley. At the beginning of the pandemic, its Innovative Genomics Institute (IGI) rapidly repurposed a 2,500-square-foot scientific lab into an automated diagnostic laboratory that could initially process more than 1,000 patient samples per day, with the ability to ramp up to 3,000 per day thanks to robotics and a streamlined workflow. Partnering with dozens of people from Thermo Fisher Scientific, Salesforce, Third Wave Analytics, and Hamilton Corp., the lab focused on not only turnaround time but also accuracy of results through automation. Their continued success, of course, still relies on a steady supply of reagents and related supplies from Thermo Fisher.<ref name="TerryCRISPR20" /><ref name="SandersUCBerk20">{{cite web |url=https://news.berkeley.edu/2020/03/30/uc-berkeley-scientists-spin-up-a-robotic-covid-19-testing-lab/ |title=UC Berkeley scientists spin up a robotic COVID-19 testing lab |work=Berkeley News |author=Sanders, R. |date=30 March 2020 |accessdate=10 April 2020}}</ref>
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| Since the pandemic's start, others have also expressed concerns about the global supply of reagents necessary to test for SARS-CoV-2. Successful testing using RT-PCR requires two different enzymes: reverse transcriptase, for converting RNA to DNA, and polymerase, for amplifying the converted DNA. These enzymes and other reagent components may be instrument-specific, and at least one component has to be sympathetic to detection of the target virus' RNA. Little of this can be prepared without a proper sequence of the virus in question. Dr. Ronald Leonard, president and medical director of Cytocheck Laboratory and medical director of the Labette Health hospital, expressed the difficulties associated with reagent manufacturing thusly<ref name="NoltingLocal20">{{cite web |url=https://www.parsonssun.com/news/coronavirus/article_99193646-7aec-11ea-a7c5-b700f82332db.html |title=Local testing delayed by lack of reagents |work=Parsons Sun |author=Nolting, R. |date=10 April 2020 |accessdate=10 April 2020}}</ref>:
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| <blockquote>With the instant demand for SARS-CoV-2 testing, the manufacturing process had to start from scratch for the SARS-CoV-2 specific components, and this did cause a lag time before reagents were available. The increased demand coupled with the decision to only allocate reagents to two national laboratories, some state health departments, and to "hot spots" has compounded the difficulty for laboratories like ours to obtain the necessary reagents to perform the testing.</blockquote>
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| Reports of COVID-19 test reagent shortages from various sources have appeared since March 2020.<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> Over time, those shortages even extended to supplies for non-COVID-19 tests such as those for strep throat, bronchitis, mycobacterial infections, urinary-tract infections, fungal infections, and sexually transmitted infections.<ref name="ASMSupply20" /><ref name="AbbottCovid20" /><ref name="WilliamsSupply21" /> In the face of these supply challenges, some have taken matters into their own hands. Noting Irish laboratories' difficulties sourcing lysis buffer (for isolating molecules of interest and keeping them stable), Cork Institute of Technology's Dr. Brigid Lucey worked with several other virologists and microbiologists early in the pandemic, as well as with pharmaceutical company Eli Lilly, to produce a custom-formulated yet high-quality lysis buffer for not only Irish laboratories but also other countries can take advantage of. "We are happy to share what we found with other countries and it’s important our scientists retain their skills to make this kind of formulation because we may need to do this again in the future if we get other pandemics," she said.<ref name="RocheIrish20" />
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| Another challenge lies in the accuracy of serology-based antibody tests, let alone how much they actually tell us about immunity. FierceBiotech's Conor Hale touched upon this in late April 2020<ref name="HaleCongress20">{{cite web |url=https://www.fiercebiotech.com/medtech/congress-urges-fda-to-better-police-evaluate-covid-19-antibody-tests |title=Congress urges FDA to better police, evaluate COVID-19 antibody tests |author=Hale, C. |work=Fierce Biotech |date=27 April 2020 |accessdate=01 May 2020}}</ref>:
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| <blockquote>Compared to molecular tests—which sequence and match the RNA of the novel coronavirus to produce a result—the FDA has described antibody tests that gauge the body’s immune system response as a less-complicated endeavor that could proceed without review, dubbed “regulatory flexibility” by Commissioner Stephen Hahn. This policy shift has led to confusion, with some antibody test developers falsely claiming their tests are FDA-approved or could diagnose COVID-19 at home. Still others have sold outrightly fraudulent tests online.</blockquote>
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| At least in the U.S., these problems are compounded by company participation in test validation of EUAs being voluntary.<ref name="HaleCongress20" /> As a late April 2020 memorandum from Congress put it: "FDA is unable to validate the accuracy of antibody tests that are already on the market, and companies are ignoring requests from the Department of Health and Human Services (HHS) to voluntarily submit their tests for validation ... FDA has failed to police the coronavirus serological antibody test market, has taken no public enforcement action against any company, and has not conveyed any clear policy on serological tests..."<ref name="SORPremim20">{{cite web |url=https://oversight.house.gov/sites/democrats.oversight.house.gov/files/ECP%20Staff%20Report%20on%20Preliminary%20Findings%20of%20the%20Subcommittee%E2%80%99s%20Coronavirus%20Antibody%20Testing%20Investigation.pdf |format=PDF |title=Preliminary Findings of the Subcommittee’s Coronavirus Antibody Testing Investigation |author=Subcommittee on Economic and Consumer Policy |publisher=U.S. House of Representatives |date=24 April 2020 |accessdate=01 May 2020}}</ref> The entire memorandum is revealing in the challenges of attempting to relax social distancing measures under the pretense of the effectiveness of antibody testing. Entities such as the University of California - San Francisco<ref name="FarleyTesting20">{{cite web |url=https://www.ucsf.edu/news/2020/04/417276/testing-tests-covid-19-antibody-assays-scrutinized-accuracy-ucsf-uc-berkeley |title=Testing the Tests: COVID-19 Antibody Assays Scrutinized for Accuracy by UCSF, UC Berkeley Researchers |author=Farley, P.; Sanders, R. |work=UCSF News |date=27 April 2020 |accessdate=01 May 2020}}</ref> and the University of California - Berkeley<ref name="SandersWhat20">{{cite web |url=https://news.berkeley.edu/2020/04/27/what-covid-19-antibody-tests-can-tell-us-and-what-they-cant/ |title=What COVID-19 antibody tests can tell us, and what they can’t |author=Sanders, R. |work=Berkeley News |date=27 April 2020 |accessdate=01 May 2020}}</ref> early on emphasized the importance of elements such as sensitivity, specificity, proper training, and the unknowns of the predictive ability of the test. Even assays running under trusted platforms such as PCR can reveal issues. For example, Thermo Fisher Scientific's TaqPath COVID019 Combo Kit, approved for EUA in March 2020, received scrutiny and updates to address issues with false-positive and -negative results<ref name="WhooleyFDA20">{{cite web |url=https://www.massdevice.com/fda-warns-on-false-results-for-thermo-fisher-taqpath-covid-19-testing-kit/ |title=FDA warns on false results for Thermo Fisher TaqPath COVID-19 testing kit |author=Whooley, S. |work=+ Mass Device |publisher=WTWH Media LLC |date=17 August 2020 |accessdate=23 August 2020}}</ref><ref name="TaylorThermo20">{{cite web |url=https://www.medtechdive.com/news/thermo-fisher-covid-19-test-flagged-for-false-positive-false-negative-resu/583682/ |title=Thermo Fisher COVID-19 test flagged for false positive and negative results |author=Taylor, N.P. |work=MedTechDive |date=18 August 2020 |accessdate=23 August 2020}}</ref>, highlighting the difficulty of, at least early on in the pandemic, balancing the need for rapidly approving test kits for emergency use while also maintaining some semblance of oversight regarding their effectiveness and proper use. This has been further hampered by an August 2020 decision that stated the FDA could not require laboratory developed tests (LDTs) to be submitted for an EUA. As the Pew Charitable Trust's Liz Richardson argued in September 2021, reversing this decision "would enable labs to continue bringing innovative and effective new tests to market quickly while empowering FDA to protect the public from faulty products that allow infection to spread."<ref name="RichardsonWith21">{{cite web |url=https://www.pewtrusts.org/en/research-and-analysis/articles/2021/09/02/with-delta-surging-fda-needs-authority-to-ensure-accuracy-of-covid19-tests |title=With Delta Surging, FDA Needs Authority to Ensure Accuracy of COVID-19 Tests |author=Richardson, L. |publisher=Pew Charitable Trust |date=02 September 2021 |accessdate=07 September 2021}}</ref>
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| Finally, while point-of-care testing, including at-home testing, has made strides in 2021<ref name="FDAInVitroAntigen21">{{cite web |url=https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-antigen-diagnostic-tests-sars-cov-2 |title=In Vitro Diagnostics EUAs - Antigen Diagnostic Tests for SARS-CoV-2 |publisher=U.S. Food and Drug Administration |date=07 September 2021 |accessdate=07 September 2021}}</ref>, their need remains apparent. Dozens of at-home tests remained in development (many of them antigen tests) at the end of 2020, and even now a major barrier is found in making them both accurate and easy for untrained people to understand and use.<ref name="WanHome20">{{cite web |url=https://www.washingtonpost.com/health/2020/10/24/coronavirus-home-tests/ |title=Home tests could help in the fight against the coronavirus. So where are they? |author=Wan, W. |work=The Washington Post |date=24 October 2020 |accessdate=18 November 2020}}</ref><ref name="McDermottInner20">{{cite journal |title=Inner Workings: Researchers race to develop in-home testing for COVID-19, a potential game changer |journal=PNAS |author=McDermott, A. |volume=117 |issue=42 |pages=25956-25959 |year=2020 |doi=10.1073/pnas.2019062117 |pmid=32999063 |pmc=PMC7584891}}</ref> And as more at-home tests continue to receive EUAs in 2021, they are still not without concern, particularly in regards to ensuring that at-home test results get reported properly and rapidly.<ref name="WanHome20" /><ref name="Crear-PerryTheHidden20">{{cite web |url=https://www.statnews.com/2020/11/05/rapid-covid-19-tests-hidden-public-health-hazard/ |title=The hidden public health hazard of rapid Covid-19 tests |author=Crear-Perry, J. |work=STAT |date=05 November 2020 |accessdate=18 November 2020}}</ref> One such early example at the end of 2020 was Lucira Health's LAMP-based Lucira COVID-19 All-In-One Test Kit, which was approved as a prescription-based at-home test, but with the stipulation that the prescribing healthcare provider would be responsible for reporting results.<ref name="RomoFDAApproves20">{{cite web |url=https://www.npr.org/sections/coronavirus-live-updates/2020/11/17/936055284/fda-approves-first-at-home-coronavirus-test |title=FDA Approves 1st At-Home Coronavirus Test |author=Romo, V. |work=NPR |date=17 November 2020 |accessdate=18 November 2020}}</ref> Such a requirement arguably can and should be put in place for at-home antigen-based testing as well.<ref name="WanHome20" />
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| As the pandemic churns through its second year, it's more important than ever for leaders across government, healthcare, and the media to continue to not spread misinformation and not make decisions based on poor scientific evidence. It will take organized efforts from multiple stakeholders—such as that found with a June 2020 NIH workshop on expanding and improving COVID-19 antibody tests<ref name="NIHExperts20">{{cite web |url=https://www.nih.gov/news-events/news-releases/experts-identify-steps-expand-improve-antibody-tests-covid-19-response |title=Experts identify steps to expand and improve antibody tests in COVID-19 response |author=National Institutes of Health |work=News Releases |date=23 June 2020 |accessdate=08 July 2020}}</ref>—to continue to find responsible solutions to the challenges we still face with this pandemic.
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| ==References==
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| {{Reflist|colwidth=30em}}
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| ==Citation information for this chapter==
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| '''Chapter''': 2. Diagnostic testing of COVID-19 and other coronaviruses
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| '''Edition''': Fall 2021
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| '''Title''': ''COVID-19 Testing, Reporting, and Information Management in the Laboratory''
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| '''Author for citation''': Shawn E. Douglas
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| '''License for content''': [https://creativecommons.org/licenses/by-sa/4.0/ Creative Commons Attribution-ShareAlike 4.0 International]
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| '''Publication date''': September 2021
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