The Pandora Report

By Rachel-Paige Casey, Biodefense PhD Student

Introduction

As we near the one-year mark into the COVID-19 pandemic, the world has suffered over 67 million cases and over 1.5 million deaths from the novel coronavirus. In the United States, total cases exceed 15 million and the death toll is climbing toward 300,000. COVID-19 has exposed critical gaps in preparedness, but also global health security in general. Beyond the severe health impacts of SARS-CoV-2, the economic and social impacts from the pandemic have proven nightmarish. As declared by the 2019 Global Health Security Index, which is the first comprehensive assessment of global health security capabilities in 195 countries, no country is adequately prepared for outbreaks, and every country has important deficiencies to address. The 63^rd Annual ABSA Biosafety and Biosecurity Virtual Conference addressed several such gaps. 

As microbial challenges develop and diversify, the biosafety and biosecurity community has to continually adapt and evolve to address issues in effective, efficient, and often imaginative ways. Antimicrobial resistance is a hot topic, as the list of resistant microbes continues to grow while the list of effective antimicrobials dwindles. There is a critical need for novel therapeutics to fight various drug-resistant infections. Recently, there has been much effort toward improving best practices in biosafety, tackling zoonotic challenges in the laboratory, and creating a flexible biosafety risk assessment framework for commercial scale cell and gene therapy manufacturing.

The 63^rd American Biological Safety Association (ABSA) Annual Biosafety and Biosecurity Virtual Conference convened the global community of biosafety and biosecurity practitioners and experts from November 4 –6, 2020. This conference focused on a broad variety of topics dealing with biosafety, biosecurity, and bioethics with an emphasis on activities and challenges related to COVID-19.

Overview of ABSA Virtual Conference Report

I attended this virtual conference along with my GMU Biodefense Program colleagues Mr. Yong-Bee Lim and Ms. Sally Huang. To provide our readership with a comprehensive report on the ABSA conference, we self-assigned sessions that we would write about. This report provides an overview, details, and comments on the following sessions:

1. Session III: Pathogen Genomics from Antibiotic Resistance to COVID-19
2. Session XI: Regulatory Updates
3. Session XIII: Biosafety Assortment – Emerging Fields of Drug Therapies & Commercial Scale Production Challenges 
4. Session XVI: High-Containment

Session III: Pathogen Genomics from Antibiotic Resistance to COVID-19

Dave Engelthaler, director of the Pathogen and Microbiome Division at the Translational Genomics Research Institute (TGen), was the invited speaker for this year’s conference, and he presented on pathogen genomics. Improvements in rapid and inexpensive genome sequencing technologies have enabled improved diagnostics and microbial surveillance, which is critical to combating the spread of antimicrobial resistance (AMR). AMR is the characteristic in which microorganisms – viruses, bacteria, and fungi – change over time and in ways that that render antimicrobial medicines futile against them. Dr. Engelthaler shared a few shocking statistics:

• Methicillin-resistant Staphylococcus aureus (MRSA) causes 80,461 severe infections and 11,285 deaths annually
• Carbapenem-resistant Enterobacteriaceae causes 9,000 drug-resistant infections and 600 deaths annually
• Drug-resistant non-typhoidal salmonella causes 100,000 drug-resistant infections and $365,000,000 in medical costs annually

These are merely a few examples of the drug-resistant diseases plaguing the human population. Antibiotic resistance proliferates as a result of selective pressure in which a population of bacteria contains a subset of antibiotic-resistant organisms that survive treatment and are able to cause new infections. Dr. Engelthaler discussed the concepts of pre-resistance, in which a minor component of a population of treated patients presents with drug resistance, and, hopefully, revealing an opportunity to detect resistance early. Quelling the spread of antimicrobial resistance requires not only complex tools for pathogen genomics, but also a One Health approach that appreciates the interconnection between humans, animals, plants, and their shared environment.

Switching gears toward COVID-19, Dr. Engelthaler described the tracking and findings of the novel coronavirus’ genomics. He explained the genomic tracking of SARS-CoV-2 as building a viral family tree, akin to using “ancestry.com for COVID.” The goal of genomic tracking is to discover where the virus came from and predict where it is going as well as identify and understand its mutations. The spike-protein D614G mutation is suspected of being the mutation that made the pandemic. The D614G mutation was first found in strains that took over Europe, but came from Asia, before hitting the United States. In January, in Arizona, a student at ASU returned home from a visit to Wuhan. This one of the first four cases in the United States; however, the viral lineage died with that case. Interestingly, there was a substantial outbreak from a strain out of Tucson and this specific regional population has this one mutation that has not been found elsewhere. Dr. Engelthaler pointed out that the popular strains of SARS-CoV-2 tend to be highly transmissible, but with low lethality.

Session XI: Regulatory Updates

Dr. Kathryn L. Harris from the National Institutes of Health (NIH) provided a briefing on the latest updates from the Office of Science Policy, including NIH guidelines with COVID-19 research and development and activities of the Novel and Exceptional Technology and Research Advisory Committee (NExTRAC). The NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules was amended in April 2019. The Guidelines set minimum biosafety requirements regarding physical containment and biosafety levels for research with recombinantly or synthetically modified SARS-CoV-2 in whole or portions of the virus. There are four risk groups for human etiologic agents defined by their relative pathogenicity for health human adults, where Risk Group 1 agents are not associated with disease in health adults and Risk Group 4 agents are likely to cause serious or lethal disease for which preventative or therapeutic intervention is not usually available. Under the Guidelines, appropriate biosafety level for conducting research with SARS-CoV-2 depends on the modifications to and manipulation of the agent: recombinantly or synthetically modified SARS-CoV-2 (whole virus) would generally require a minimum of biosafety level 3 containment, whereas experiments using only a fragment of the virus may be able to be safely conducted at a lower level. SARS-CoV-2 clinical trials involving the administration of recombinant or synthetic vaccines that are subject to the NIH Guidelines require review and approval by the Institutional Biosafety Committee (IBC).

NExTRAC focuses on the scientific, safety, and ethical issues associated with emerging biotechnologies, such as gene editing, gene drives, synthetic biology, and neurotechnology. Additionally, NExTRAC serves as a public forum for transparent discourse on challenging issues, a source of advice to the NIH Director, and a resource for the scientific community and general public. The Working Group on Biosafety Guidance and Conditions for Field Release of Gene Drive Modified Organisms provides advice on the diverse applications and species that may be used in gene drive research with different risks as well as the knowledge and conditions should be in place to help ensure that field release research of gene drive-modified organisms could be conducted safely and ethically.  

Dr. Thomas J. Cremer from the Centers for Disease Control and Prevention (CDC) discussed the response of the Import Permit Program (IPP) to the COVID-19 pandemic. The program regulates the importation of infectious biological materials that could cause disease in humans in order to prevent their introduction and spread into the US. In 2012, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) became a Select Agent and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) requires additional permits for distribution. Given that all coronaviruses have a positive-stranded RNA genome, the complete RNA genome is regulated by the CDC and subsequent distribution requires additional permits. As a novel coronavirus, SARS-CoV-2 is not currently a Select Agent; however, it is subject to an additional permit for subsequent transfers. Isolates or cultures of SARS-CoV-2 and materials known or suspected to contain the virus require a different IPP application than unembalmed human known or reasonably expected to be infected with SARS-CoV-2. In response to the pandemic, inspections by the Division of Select Agents and Toxins were made virtual until September. IPP is working to expedite all requests for SARS-CoV-2 for research and development.

Dr. Aufra C. Araujo, also from the CDC, highlighted the biosafety contributions of the Division of Laboratory Systems (DSL) to the COVID-19 response. As of 26 October, 7,478 CDC personnel are supporting the pandemic response, 131 COVID-19 studies have been published in the Morbidity and Mortality Weekly Report (MMWR), 141 million COVID-19 tests have been conducted in US laboratories, and 34.4 million uses of the Coronavirus Self-Checker have occurred. The DSL’s role in the response includes laboratory biosafety guidance, addressing biosafety inquiries, and supporting development of training and educational materials. Since the start of the pandemic, DLS has received many inquiries regarding data and reporting, situational awareness, sample collection and handling, logistics, testing, and biosafety. As the pandemic persists, and cases surge, the DLS continues to provide laboratory guidance and training.  

Finally, Dr. Daniel Tuten from the CDC described the Federal Select Agent Program (FSAP) Laboratory Examination Tool (LET). The FSAP regulates the possession, use, and transfer of biological select agents and toxins and it is jointly managed by the Division of Select Agents and Toxins (DSAT) at the Centers for Disease Control and Prevention (CDC) and the Agriculture Select Agent Services (AgSAS) under the Animal and Plant Health Inspection Service’s Agriculture Select Agent Services (APHIS) at the US Department of Agriculture (USDA). The primary purpose of the FASP-LET is to aid FSAP-regulated entities to conduct annual, internal inspections. Section 9(a)(6) of the select agent regulations requires a Responsible Official (RO) to certify that an annual inspection is performed for each registered space where select agents and toxins are stored or used in order to assess compliance with the requirements of the select agent regulations. The tool is available online and all data in the system – including deficiencies, comments, and corrective actions – are encrypted. The FSAP-LET is intended to help laboratories comply with the select agent and toxin regulations, but it is not exhaustive and does not address all regulatory requirements, thus, regulated entities are responsible for ensuring they are compliant. In late 2019, the tool was moved to the electronic FSAP information system, which improves efficiency and the exchange of information for collaboration.

Session XIII: Biosafety Assortment – Emerging Fields of Drug Therapies & Commercial Scale Production Challenges 

Dr. Susan E. Vleck from Stanford University covered zoonotic challenges in biosafety, including a case study of a possible laboratory acquired infection (LAI), and how Stanford’s Animal Research Occupational Health and Safety Program has facilitated collaborative improvements between environmental health and safety (EH&S) and the Veterinary Services Center. The Animal Research Occupational Health and Safety Program is a central resource for Stanford researchers and staff who are working with animals, and particularly for those working with hazards overseen by EH&S. The program was created to address animal-related EH&S queries, trainings or assessments, and assist Occupational Health by advising on the medical surveillance program. In biosafety, moving from in vitro to in vivo creates additional issues in which the biological agent must be considered along with its tropism, replication and spread, but also issues such as animal housing and potential shedding of the agent. Dr. Vleck pointed out that zoonoses can occur within a research colony in three situations: (1) infected animals are introduced into the colony; (2) a human transmits a disease to the animals; or (3) research is conducted with agents that can cause zoonoses and the necessary safety protocols are not followed. Such safety failures are especially concerning for laboratories that work with the “big three” zoonotic diseases: Coxiella burnetii in sheep, Herpes B virus in non-human primates, and tuberculosis or MMR in humans. In order to protect personnel and research subjects, Stanford employs a three-pronged approach: (1) animals are tested before arrival, quarantined upon arrival, and then tested again; (2) any staff who has routine contact with animals may undergo medical surveillance; and (3) all personnel are educated on zoonotic risks associated with the big three diseases.

In 2018, a potential exposure was reported, which involved a person working male sheep that had oral and nasal lesions upon arrival. These sheep were suspected to be infected with Orf, a viral sin disease caused by a parapoxvirus, and classified as a Risk Group 2 agent. Transmission can occur should a human come in direct contact with a lesion or fomite, and the individual in question did present with a rash that spread from the upper right extremity to the upper left extremity and torso. Given that this event created a concern over disseminated disease, a collaborative investigation into the case was carried out, and the exposure route was likely a floor drain. As a result of this incident, several practices were updated, to include a more thorough cleaning of rooms and tools, requiring arm covers as part of minimum PPE, establishing formal training on PPE and zoonoses, and designed door and pen signage for when any animal in the colony had lesions or a positive test. This incident also highlighted the need for improved communication between departments; however, the after-action efforts enabled an improved understanding on the roles and responsibilities of each group, and the clear need to communicate.

Kim DiGiandomenico from AstraZeneca presented on an environmental health and biosafety risk assessment framework for commercial scale cell and gene therapy manufacturing, developed by the Biophorum or Cell and Gene Therapy (CGT). Cell and gene therapies aim to treat diseases by altering genes in specific cells and insert those cells back into the body. The Biophorum is a global collaboration comprised of industry leaders and experts throughout the biopharma value chain. The CGT was formed in 2018 as the first environmental health and safety and biosafety (EHS&B) Biophorum. The goals of the CGT are to develop best practices and standards, improve risk controls, increase the speed of learning, and help regulatory agencies in drafting guidance or policies around CGT development and manufacturing. The existing industry risk assessment methodologies lacked guidance related to the CGT-associated risks and commercial scale CGT manufacturing as they were created for monoclonal antibody and biologic production. To fill in this gap, a framework for EHS&B professionals includes a Risk Assessment Template that alerts the reader to the “complexity of commercial scale manufacturing, areas to assess, potential questions to ask and other pertinent parties who may input to the risk assessment.” The resulting safety profile devised by a cross-functional team helps mitigate risks related to product biological contamination, failures or breaches of the system, spills, material and waste flows, and surface cleanability. Ms. DiGiandomenico emphasized that risk assessments are a shared responsibility by multiple disciplines at all levels of an organization and that there does not exist a one-size-fits-all risk assessment scheme, because risk varies based on infrastructure, scale, and personal competencies.

Session XVI: High-Containment

Fahim Manzur from the Plum Island Animal Disease Center in New York detailed the four lessons learned from bringing a new high-containment effluent decontamination system (EDS) online, which resulted in some costly mistakes. Leaks were observed from newly installed stainless steel piping sections placed below storage tanks after several months of testing with clean water, causing microbiologically induced corrosion of the piping. The existing piping was replaced with carbon steel, the diameter was decreased to increase flow rate, and the thermal and liquid decontamination of all storage tanks and piping was conducted. There was a potential Select Agent release event when hose lines suffering mechanical wear failed on multiple cook tanks during the decontamination cycle. To mitigate the issue, piping was rearranged to reduce turbulence on the hoses and floating sleeves were added. A third lesson from the buildup of solids in the system required a rework of the force main (a pressurized pipe that transports sewage flows under pressure) and the installation of a redundant force main. The final lesson revolved around the failure of components in a seawater-based secondary cooling system after 18 months of use, which was repaired by reinstalling all secondary cooling heat exchanger bundles and developing a future plan to implement a different type of system. Each of these lessons cost $13,000 to $560,000 for a total of $1,064,000. Manzur’s example of pricey lessons learned emphasizes the importance of learning from other facilities, conducting root cause analyses to mitigate failures, and understanding the cost of up-front redundancies versus the cost in terms of money, time, and work to operations to handle failures.

Sheryl Major, a Biosafety and High-Containment Officer at the University of California (UC), discussed the management of high-containment facilities for the future. There are several High-Containment Lab Initiatives at UC spanning biosafety level 3 (BSL3) laboratories, COVID-19 research, and governance and structure. A BSL-3 laboratory requires biological safety cabinets, containment equipment, powered air purifying respirators, Tyvek suits, sleeves, and disposable gowns. After several laboratory incidents at the CDC and FDA involving anthrax and smallpox became high publicized, UC decided to evaluate its BSL-3 program with a focus on safety and consistency and established the Biosafety/Biosecurity Task Force. The goals of the Task Force included establishing a system-wide high-containment laboratory oversight committee and groups, designating high-containment laboratory directors, offering training courses, performing site surveys at BSL-3 laboratories, and conducting biohazardous materials inventories. These initiatives successfully led to the development of minimum standardized training requirements, annual budget models for BSL-3 laboratories on campus, decommissioning checklists, annual facility verification recommendations, and a design standard for BSL-3 laboratories.

Andrea Smida, a Biosafety Officer at the University of Saskatchewan in Canada, told the Cinderella story of Blastomyces dermatitidis, a Risk Group 3 fungus, requiring a Containment Level (CL) 3 facility for any in vitro and in vivo work, that is the causal agent of blastomycosis. A local risk assessment of the fungus was conducted in a CL-2 laboratory and small animal facilities at the University of Saskatchewan in Canada for a research group in the College of Pharmacy and Nutrition. The team wanted to conduct an in vitro evaluation of the efficacy of a monoclonal antibody in killing B. dermatitidis and an in vivo evaluation of the efficacy and long-term toxicity of the radioimmunotherapy. In short, the team wanted to find out if this Risk Group 3 fungus could be used in an enhanced CL-2 or CL-2+ facility. A pathogen risk assessment determined B. dermatitidis as a human and animal RG3 organism that can be worked on in a CL-2 facility adhering to CL-3 operational processes. This determination was based on the thermal dimorphic nature of the fungus, which means that the yeast form is not as pathogenic and communicable in comparison to the spore form, and the fact that the yeast form can be easily maintained when the temperature is 37°C or lower. The “happily ever after” of this story is that the B. dermatitidis research was initiated in April 2019 when the samples were supplied to the team. Currently, there is no Blastomyces work being conducted and the fungus is sitting in storage at -80°C; however, future work is planned for early 2021. Future implications of this Cinderella story include a new Public Health Agency of Canada-Canadian Food Inspection Agency biosafety directive for Risk Group 3 fungi at CL-2 laboratories.

Heather Blair, an Associate Biosafety Office at Colorado State University, trains principal investigators, visiting scientists, post-docs, and graduate and undergraduate students on how to work safely in BSL-2 and BSL-3 laboratories. Her first point is about the difference between disinfecting and autoclaving biological liquid for disposal. Disinfection is a process that removes many or all microorganisms, except bacterial spores, on inanimate objects by applying antimicrobial pesticides. Disinfectants include acids, alcohols, aldehydes, alkalis, biguanides, oxidizing agents, halogens (hypochlorite and iodine), phenolics, and quaternary ammoniums. Sterilization is a process that removes or eliminates all forms of microbial life using physical or chemical methods. Sterilization destroys all microorganisms on the surface of an article or in a fluid to prevent disease transmission. Autoclaving is used to sterilize liquids as well as inanimate objects and surfaces. In order to maintain safety and protect samples, Blare recommends spraying a surface that is clean, such as a towel or cloth, instead of the contaminated surface and then wiping down the contaminated area. Proper gloves must be donned when disinfecting and sterilizing to protect staff and samples. Biological safety cabinets (BSCs) require undisrupted airflow and, for staff safety, a researcher would work at least 4 inches from the front air vent in the middle. Additionally, work should be done horizontally such that there is a clean to dirty flow while working in the BSC.

Embracing Improvement  

The biosafety and biosecurity community faces constant challenges from microbial dangers, but also from the maintenance of safe laboratory environments in order for research to continue. Dr. Kathryn L. Harris highlighted the regulatory updates made to address minimum biosafety requirements regarding physical containment and biosafety levels for research with recombinantly or synthetically modified SARS-CoV-2. Dr. Daniel Tuten described the Federal Select Agent Program Laboratory Examination Tool (FSAP-LET), which debuted a new system to increase efficiency by greatly enhancing information exchange with FSAP and collaboration. Kim DiGiandomenico emphasized the importance of risk assessments in order to mitigate risks arising in the laboratory. Fahim Manzur detailed how lessons were learned and improvements were made from a series of failures at a facility with a new high-containment effluent decontamination system. Heather Blare trains researchers and students on how to work safely in BSL-2 and BSL-3 laboratories. These examples show the dedication of laboratory scientists and researchers to improvements in safety and best practices.  

By Yong-Bee Lim, Biodefense PhD Candidate

Introduction

With events like the COVID-19 pandemic, it is easy to focus solely on the numbers and the devastating impact it has had on the economy and politics. As of November 4^th, the World Health Organization (WHO) reported over 48 million cases of COVID-19, resulting in over 1.2 million deaths globally. At over 9.5 million confirmed cases and upwards of 234,000 deaths, the US accounts for nearly 20% of all COVID-19 cases and deaths.

This pandemic also highlighted vulnerabilities in the medical product supply chain. It has significantly hampered the transportation of supplies as some nations have closed their borders in an attempt to get a handle on the spread of COVID-19. In addition, a global dynamic has emerged where demand for personal protective equipment (PPE) has far exceeded domestic and international supplies.  

This incident has highlighted clear tensions that exist between the need to cooperate on an international scale and the fundamental need for individual states to prioritize the health and well-being of their citizens. This has had significant impact in areas like pharmaceutical research, development, and distribution – in particular, the issue of distribution raises ethical questions about equitable access to treatment during a global pandemic.

During the 63^rd American Biological Safety Association (ABSA) Annual Biosafety and Biosecurity Virtual Conference, a global community of biosafety and biosecurity practitioners and experts convened from November 4 –6, 2020. This conference focused on a broad variety of topics dealing with biosafety, biosecurity, and bioethics with an emphasis on activities related to COVID-19.

Overview of ABSA Virtual Conference Report

I attended this virtual conference along with my GMU Biodefense Program colleagues Ms. Rachel-Paige Casey and Ms. Sally Huang. To provide our readership with a comprehensive report on the ABSA conference, we self-assigned sessions that we would write about. This report provides an overview, details, and comments on the following sessions:

1. Session IV: Decontamination Panel
2. Session V: Bioethics and Biosafety Panel
3. Session VII: Outreach and Training
4. Session X: Coronavirus Inactivation and Challenges in Coronavirus Vaccine R&D

Session IV: Decontamination Panel

As COVID-19 continues to rage throughout the United States, healthcare facilities need solutions to supply chain issues. One option it to try and acquire new supplies of PPE gear. Unfortunately, global supply chain issues and the rise of counterfeit and mis-advertised products pose significant challenges to this option.

The other option is to find ways to repurpose used PPE. For healthcare facilities, this option offers the advantages of availability and minimal transport compared to procuring new PPE. However, the major obstacle for this option is researching, developing, and testing PPE decontamination protocols in real time.

The decontamination panel consisted of Drs. Antony Schwartz (Duke University), Andrea Vogel (National Institutes of Health [NIH]), and Brian O’Shea (Battelle). These experts discussed three different PPE decontamination efforts during the on-going COVID-19 pandemic – the research and development of two different protocols using hydrogen peroxide vapor to decontaminate and reuse N95 respirators and powered air-purifying respirators (PAPRs), as well as Battelle’s development of a vapor phase hydrogen peroxide technology to accomplish the same goals.

Each panelist described the research, development, and protocol calibration of decontaminating and reusing PPE as difficult. Unexpected challenges arose as groups tried to develop successful protocols for reusing PPE. A common thread across the three presentations included dealing with PPE soiled with makeup – in all three decontamination efforts, masks soiled with makeup were taken out of the decontamination and reuse rotation to err on the side of caution. In addition, each panelist described logistical obstacles they had to overcome to scale their decontamination efforts to meet the demand of reusable PPE – this meant finding and using large, dedicated spaces with temperature, environmental, and vaporized hydrogen peroxide release controls, as well as developing special racks and hangers to allow for proper PPE decontamination and drying. A third major challenge to overcome was efficacy – proving that the masks had both been decontaminated and had not degraded in performance.

Despite these obstacles, each panelist pointed towards clear evidence of success. Dr. Vogel noted in her section that over 38,000 N95 masks had successfully been reprocessed, Dr. Schwartz discussed how his project’s protocol have repurposed over 10,000 N95 masks and a significant quantity of PAPRs, and Dr. O’Shea pointed to how Battelle’s overcame logistical obstacles to help address PPE shortages through its network of over 60 Critical Care Decontamination System sites across the United States.

Session V: Bioethics and Biosafety Panel

ABSA traditionally considers itself as an organization that focuses on biosafety and biosecurity, which is apparent in the title of this conference: 63^rd Annual Biosafety and Biosecurity Virtual Conference. However, with this year’s heavy emphasis on COVID-19 issues, it is impossible to talk about addressing COVID-19-related issues without having a conversation about incorporating at least one session on bioethics – the study of ethical issues, framing paradigms, and implications due to advances in areas like medicine and the life sciences.

The bioethics panel consisted of Drs. Stefen Wagner (Biorisk International) and Brynn Welch (University of Alabama, Birmingham). Dr. Wagner provided a brief overview of the foundations of bioethics a field whose guiding principles consist of four main considerations, or “pillars”: nonmaleficence, justice, beneficence, and autonomy.

Dr. Wagner described two examples of bioethics that were salient to both the ABSA audience and modern dilemmas. The first example involved popular commercial genetic testing kits and databases like those of 23andMe and Ancestry.com. While people have used these commercial tests to discover their potential historic ancestry based off their DNA, Dr. Wagner noted that there are implications to companies having such unique, personalized data at their disposal. His second example involved a recent COVID-19-related hot topic: the efficacy and desirability of so-called “immunity passports.” Immunity passports are a framework that would allow those previously infected with COVID (and thus, hopefully, immune) to travel, work, and interact with others as they had before the pandemic. In regard to immunity, he noted that exposure to COVID-19 results in higher IgG and IgM antibodies against the virus, which means it is quite likely that the body is primed to address COVID-19 and provide at least some degree of immunity. The caveat he offers is that the efficacy and longevity of immunity remain in question, and scientists can only find that out with more research over the years to come. Dr. Wagner raised a number of points about how effective such a framework would be, as well as raising the question of unintended consequences – given the desirability of immunity passports, what is the extent to which people may deliberately infect themselves, commit fraud and theft, and even use immunity passports as a way to discriminate against others?

Dr. Welch then presented on a hot topic at the intersection of bioethics and COVID-19: the bioethics of COVID-19 vaccine trials. During her presentation, she reiterated that she understood both the need and the desirability of finding a vaccine for COVID-19. However, she also wanted to raise points about how an accelerated COVID-19 vaccine may not be in the best interest of the rights of individuals, communities, and society.

Dr. Welch discussed four main issues that she saw regarding the bioethics of COVID-19 vaccine research and development. First, she expressed concern that individuals may be feeling social and biological coercion to participate in vaccine trials, which can meaningfully undermine a person’s autonomy. Second, she discussed the difficulties of truly communicating risks to test subjects, which raises questions about how informed participants can be when giving consent. Third, she noted that test participants may not be getting adequate compensation in drug trials, or that attractive compensations may skew the pool of participants to those with greater financial needs. Finally, she brought all her former considerations together to ask how practitioners can balance the welfare of research subjects against life-saving and economy-saving scientific research.

Session VII: Outreach and Training

Even prior to the pandemic, ABSA members were engaging in outreach and training to new audiences participating in the life sciences. This partially has to do with the expansion of the life sciences research and practices outside of academia, industry, and government as highlighted by groups such as the Do-It-Yourself Biology (DIYBio) movement. In addition, biosafety experts have realized that students, faculty, and staff may have to deal with potentially infectious materials during their work and everyday lives.

The outreach and training panel consisted of Ms. Irene Mendoza (Arizona State University, Tempe), Ms. Janelle Runberg (Northern Arizona University, Flagstaff), and Dr. Muhammed Karahan (Pendik Veterinary Control Institute, Istanbul, Turkey). Each of the panelists discussed unique outreach and training initiatives to make their respective communities and institutions a safer space from a biosafety perspective.

Ms. Mendoza presented on three main activities she helped organize and facilitate to promote outreach and training. First, she discussed an initiative called the “Eye Promise Campaign” – an effort to promote a culture of safety at ASU by setting expectations for those doing work that require safety glasses. This “Eye Promise Campaign” included flyers, presentations, and hands-on activities like “Blinging for Safety,” where prescription safety glasses were provided at no cost for individuals to decorate and use during their lab work. The second initiative she discussed was the Arizona State University (ASU) Open Door event, where ASU invites local community members to visit and explore any of the 5 ASU campus locations. Free and open to the public, the ASU Open Door event also includes hands-on biosafety and biosecurity activities at booths and labs in conjunction with FBI partners, including “Ask an FBI Agent,” “Bio Bistro,” “Lab Made Foods,” and “A Biosecurity Investigation.” She then discussed a STEM initiative for students in grades 6 – 12 called the “Chief Science Officers” program, where students participate in leadership training sessions, attend meetings with local business and civic leaders, and receive direct mentorship.

Ms. Runberg’s work in outreach and training was driven by both her passion for biosafety and a desire to ensure that safety is an integral part of the learning and working environment at Northern Arizona University (NAU). To this end, she helped improve biosafety pre-COVID by rolling out an online training and hazard management system called “BioRAFT,” expanding the aperture of biosafety messaging and training to students and faculty that may have interactions with sharps (which include items like needles, scalpels, and other sharp objects), and increasing in-person training frequency and direct outreach to different departments at NAU. While COVID presented significant challenges to the direct availability of a biosafety person for training, Ms. Runberg generated training videos and presentations that she self-created to continue educating others in a socially distanced fashion.

Dr. Karahan’s presentation focused on finding ways to minimize biosafety risk for individuals that visited Pendik Veterinary Control Institute – a veterinary research institute in Istanbul, Turkey, which includes one BSL-3 laboratory out of 21 labs total. This government laboratory operates with 188 trained employees, but also has a guesthouse on campus where visitors can stay. Dr. Karahan discussed how those that often stayed in the guesthouse were typically unaware of the potential risk from the institute. To fill this gap, the institute obtained permissions from the government to develop and provide a set of emergency procedures for guesthouse visitors. Guesthouse visitors were given pre- and post-survey evaluations to test the efficacy of knowledge transfer and retention during their visit, with Dr. Karahan reporting that the surveys indicated that guests gained awareness and retained emergency procedures over the course of their stay.

Session X: Coronavirus Inactivation and Challenges in Coronavirus Vaccine R&D

Many countries around the world have experienced varying success with the different ways they have approached COVID-19 in terms of preparedness, response, and mitigation. One key element that exists across all countries is the importance of developing an effective vaccine. To this end, it is important to understand how viruses like COVID-19 can be inactivated and studied for the research and development of vaccines.

This panel consisted of Mr. Cary Retterer (ABL, Inc.) and Dr. Daniel Eisenman (Advarra). Mr. Retterer’s talk focused on developing and confirming protocols for viral inactivation in different conditions – from cell monolayers and tissue samples to concentrated virus stock and sera. After a detailed description of the protocol and results, Mr. Retterer discussed the challenges associated with consistent and effective viral inactivation. He noted that inactivation testing is resource intensive. In addition, he stated that filters tended to clog and interrupt the process, particularly for larger samples like tissue samples. Third, he noted that in vivo samples were particularly challenging to accommodate for viral inactivation. And finally, he provided a recommendation for a harmonized, pan-institute repository of inactivation methods that could leverage industry-wide experience and expertise, as well as minimizing the number of animal specimens that may then be required for inactivation testing.

Dr. Eisenman then presented on the major trends in scientific advances in clinical trials involving gene therapy and gene-modified cellular therapy. Dr. Eisenman has a unique vantagepoint on this topic as he has participated in providing institutional review board (IRB) oversight for 100% of Operation Warp Speed’s (OWS) COVID-19 vaccine trials as an employee of Advarra. In his discussion of Coronavirus vaccine R&D, he explained the basics of how vaccines work, as well as how all the vaccine research groups are utilizing some form of recombinant or synthetic nucleic molecules. While he noted the promise of these types of gene therapy approaches to future vaccine and treatment development, he also highlighted how these approaches can pose unique challenges in conducting future risk assessments in this area. A few issues practitioners will need to consider with gene therapeutic approaches are the genetic modifications that are occurring (to the vector, to the antigen, and the potential risk of recombination), the implications of viral shedding with gene-modified products, and the unique risks that may be involved with at-risk populations that may interact with study participants.

Necessity is the Mother of Invention – A Woven Thread

Each panel incorporated presentations and discussions about the challenges that COVID-19 has presented to operating safely, securely, and ethically in the life sciences. The pandemic has made resources scarce, in-person collaboration and outreach virtually impossible, and raised many questions on what the best approach is to bring about the end of the pandemic.

What this conference has shown is that necessity is the mother of invention. Each of these panels highlighted how innovation can happen in the face of adversity. Supply chain failures helped generate robust and sustainable PPE decontamination and reuse models in different settings. Incorporating bioethics in a time of great societal instability and erosion of trust in the institution of science is the first step in building a collective vision of what is and is not acceptable as we try to move to a post-COVID era. The inability to convene did not stop biosafety outreach efforts to teach other safety professionals and the broader community about how to handle and dispose of sharp objects, as well as how to properly don and doff PPE. Finally, while OWS was not the funder of the most promising therapeutic researched and developed by Pfizer, it has served as a demonstration of a moonshot challenge that may enable vaccines to be researched, developed, and deployed significantly more quickly than the typical 10 – 15-year timeline.

By Sally Huang, Biodefense PhD Student

Introduction

With the United States amid its third wave of the COVID-19 pandemic, trepidations regarding the safety and well-being of the population continue to weigh upon the country. These worries also translate to the healthcare, public health, and scientific communities, highlighting risks with improper or poor biosafety and biosecurity measures. The 63^rd Annual Biosafety and Biosecurity (ABSA) Conference kicked off its 2020 schedule by addressing these COVID-19-associated implications. Even as the conference was held virtually in light of the pandemic to prevent large gatherings and subsequent spread of disease, ABSA did not disappoint; the event operated via an interactive virtual lobby platform featuring experienced panelists, live virtual presentations, and exhibits showcasing the latest biosafety and biosecurity experiments, products, and services. Panelists displayed an assured attitude of commitment to utilizing lessons learned so far from the COVID-19 pandemic to foster a shared sense of responsibility, present biosafety and biosecurity best practices as well as forecast its potential for restructuring infectious disease preparedness and response.  

Overview of ABSA Virtual Conference Report

I attended this virtual conference along with my GMU Biodefense Program colleagues Ms. Rachel-Paige Casey and Mr. Yong-Bee Lim. To provide our readership with a comprehensive report on the ABSA conference, we self-assigned sessions that we would write about. This report provides an overview, details, and comments on the following sessions:

1. Session II: Spotlight on COVID-19
2. Session IX: Biosafety Program Management
3. Session XIII: Biosafety Assortment
4. Session XV: Ag COVID Research and Response

Full session line-ups from the virtual 2020 ABSA Conference can be found here.

Session II: Spotlight on COVID-19

Notable panelists discussed the importance of enhancing and promoting biosafety in laboratories as the COVID-19 pandemic presented numerous challenges to the global community, but also allowed for novel areas of research. Concomitant to COVID-19 research and development (R&D) is the issue to prioritize biosafety and biosecurity to protect scientists and researchers as well as prevent laboratory accidents that may further proliferate the disease. Dr. Aderemi Dosunmu (Columbia University) addressed how university laboratories are ramping up BSL-2 labs to ensure a safe and secure research environment. This included personnel training, increasing knowledge about personal protective equipment (PPE), increase accessibility and availability of biosafety resources, and also highlighted the role of oversight committees to support institutional biosafety practices. By committing to these steps, scientists and biosafety officers alike will feel more empowered and at ease in conducting their work in research environments.

Luis Alberto Ochoa Carrera (Mexican Institute for Social Security) provided a noteworthy look into how Mexico juggled biosafety and biosecurity in the face of various infectious disease outbreaks. In discussing Mexico’s propensity to infectious diseases, Carrera lays out a candid reflection of Mexico’s experiences with the H1N1 influenza pandemic (2009), cholera (2013), chikungunya (2014), preparedness and response measures taken against Ebola (2014), Zika and measles (2016), and Dengue fever (2019). Mexico utilized lessons learned from each outbreak to generate specific actions to improve their biosafety and biosecurity measures, as well as raise awareness on how other laboratories and hospitals should prepare and respond to infectious diseases. An earthquake in Mexico City compounded the difficulties already presented by COVID-19. This complicated public health matters, biosafety, and biosecurity; however, Mexico displayed resolve and was able to handle the challenges in COVID-19 by implementing risk assessments, strengthening technical and administrative exchange of information, and improving laboratory and public health infrastructure over the years. Thus, Carrera reveals the value of learning and using past experiences as a basis to improve biosafety and biosecurity practices so that countries may be poised to handle future critical emergencies.

We also got an inside look into how biosafety training strengthened COVID-19 responses in Pakistan through The Pakistan Biological Safety Association’s (PBSA) biosafety and risk management (BRM) training program, which began in 2014. Mashaal Chaudri (Pakistan Biological Safety Association) revealed how participants not only learned proper biosafety etiquette, but also successfully integrated the knowledge and skills they have acquired during COVID-19 response efforts. Hence, this is one of the many cases presented in the 2020 ABSA Conference exhibiting the significance of interactive biosafety and biosecurity experiences to incorporate interdisciplinary approaches to affect meaningful change and response when needed. Biosafety and biosecurity programs have also shown how they can act as galvanizing tools to strengthen communication and cooperation between the public and scientific communities in order to build sustainable and strong infectious disease responses.

Channing Sheets (Division of Occupational Safety & Health, San Francisco, CA) recognizes that some guidelines may not be applicable to certain circumstances. In which case, it is important to take initiative and help establish new guidelines that better reflect the scenario in question. This was the case when Sheets discussed preferring the California Aerosol Transmissible Disease (ATD) guidelines over that of the Center of Disease Control and Prevention (CDC) as CDC’s version lacked non-mandatory language to adequately enforce their guidelines. Yet, COVID-19 posed queries and challenges in interpreting the California ATD standard. To confront this, Sheets helped establish standards, such as California’s own airborne infection isolation guidelines, and recommendations to better inform the scientific community on how to encounter novel pathogens. These standards should be applied when encountering novel pathogens. This further comes to show the ability of lessons learned from past disease outbreaks to be translated to current events helps ramp up preparedness, readiness, and response.

Session IX: Biosafety Program Management

ABSA has been a strong advocate for inspiring institutions to establish cultures of responsibility in the life sciences to ensure that biosafety and biosecurity practices are upheld in laboratory and hospital settings. This is especially pertinent to rising dual-use concerns of advancing biotechnologies. Dr. Daniel Green (Stanford University) presented the need to foster a shared sense of responsibility among all employees by setting overall goals or objectives that allow employees to coalesce. This would promote biosafety and biosecurity efforts and achievements as a collective experience for all. Dr. Green also demonstrates how the International Genetically Engineered Medicine (iGEM) competition – a unique opportunity in which students push the boundaries of synthetic biology – serves as an example in which an interactive scientific experience can be molded with a culture of responsibility to produce exciting innovations. Further studies on how scientists perceive and mitigate risk, as well as scientists’ attitudes toward biosafety and biosecurity will help empower social responsibility. Even though institutions may have their own particular biosafety and biosecurity goals, encouraging engagement and providing training and skills will help reinforce the applicability and pertinence of these fields.

Alongside promoting biosafety and biosecurity practices, Dr. Meghan J. Seltzer (ABSA) addressed how the significance of outlining benchmarking guidelines should not be overlooked. Benchmarking, a method of capturing performance metrics, maintains its benefits as it allows for efficient use of resources, stimulates creativity, and identifies areas for improvement, but also possesses its own hazards by leading researchers to ignore context or letting confirmation or availability biases take over. To ensure best practices in benchmarking, researchers need to invest in proper preparation in anticipation of various scientific scenarios, devote time in understanding the full context of the issue at hand, keep open minds, and foster critical thinking mindsets to tackle the challenges ahead. These steps do not reflect any rigid formula or strategy, but do encompass essential elements in assuring that researchers learn the proper applications of benchmarking.

Dr. Richard G. Baumann (National Institutes of Health) concomitantly presented the need to keep research registrations relevant and organize committee reviews to inform Institutional Biosafety Committees (IBC) in order to compensate for the unpredictability of change. As research evolves, newly added procedural details may increase risk, thus IBCs should be updated to reassess projects as necessary. Dr. Baumann presents electronic registration practices as a helpful solution enabling periodic reviews of projects and building strong communication ties with entities, like the Institutional Review Board (IRB). Moreover, it would help bring novel research practices to the attention of the IBC for integration into modern scientific protocols. These developments would have to be sustained for the long-haul as Dr. Baumann notes that biosafety is an endeavor requiring effort and coordination and is not an issue that can be mastered within a singular event. Biosafety is rooted in communication and relies on a shared sense of responsibility to promote institutional unity and support. Therefore, by engaging employees, researchers, and communities in lively interactions and discussions, Dr. Baumann is confident that employees and institutions would be more willing to embrace necessary changes for upholding biosafety.

Dr. Kara Held (Baker) presented the results of her experiment conducted with Baker biosafety cabinets (BSC), which tested the myth of whether overcrowding a BSC can lead to a loss of BSC protection. In a two-part experiment, it was revealed that the BSC can handle up to 75% coverage (with no items covering the grille of the BSC) while still being compliant with Standards Organization (ISO) Class 5 before losing air cleanliness. Then, aerosol microbiological testing revealed that more than 50% coverage within the BSC can lead to a loss of personnel protection. Proving the myth that BSC overcrowding can, indeed, lead to loss of personnel protection shows the importance of proper management and use of equipment to supplement conventional biosafety rules.

Session XIII: Biosafety Assortment

This panel emphasized the role of zoonotic challenges and environmental health in biosafety. Dr. Susan E. Vleck (ABSA) described potential biosafety issues associated with zoonotic disease research that involve animal interactions. Whether an expert or a novice, laboratory personnel and husbandry staff should be informed on best practices for how to study and interact with animals while protecting their own well-being as well as the animals. Ignorance of the relevant knowledge and skills can potentially cause further spread of disease. Methods reducing these risks will rely on a combination of veterinary, occupational health, and biosafety perspectives. More importantly, communication strategies are key to improving PPE and training updates, such as those that were solidified with the creation of the Animal Research Occupational Health and Safety Program. With this program streamlining incident investigations, risk assessments, and implementation of programmatic changes, communication and safety for researchers and staff were improved, demonstrating how a top-down integrative approach underpins biosafety for personnel and animals alike.

Kim DiGiandomenico (ABSA) similarly addressed the importance of discussing and enforcing occupational health and safety risk considerations to clinical trials and patient safety when conducting commercial scale cell and gene therapy. In order to do so, partnerships must be created across industry and supply chains to foster industry sharing, learning, and development of best solutions for implementation. By highlighting the nexus of environmental health, biosafety, and risk assessment as a shared responsibility affecting multiple disciplines at all organizational levels, commercial scale manufacturing can become a more streamlined process with tailored handling and management controls.

Session XV: Ag COVID Research and Response

As the current COVID-19 pandemic continues to wreak havoc upon the international community, scientists are conducting animal research to assess susceptibility of various species to SARS-CoV-2 (COVID-19) as well as associated biosafety implications. Angela Birnbaum (ABSA) reflected upon the need to establish robust biosafety and biosecurity infrastructure for animal research to safeguard personnel and animal safety when she and her laboratory received their first samples of SARS-CoV-2. This includes implementing proper training/teaching, safe sample movement out of BSL-3 laboratories, and quality assurance. Not only do these steps promote a safer and more secure work environment, but it also enables personnel to more effectively mobilize resources when handling extra workloads brought on by the pandemic.

Dr. Tony Schountz (Colorado State University) then presented his unique findings on whether certain species of bats and rodents were susceptible to SARS-CoV-2 and also discussed best practices in handling animal research. One of the biosafety concerns when studying Jamaican fruit bats during their investigation was preventing bats’ teeth from breaking vital PPE equipment, which could have caused significant consequences for the researcher. Subsequent studies of the Cricetidae species (i.e., Syrian hamsters) illuminated overlap with human ACE-2 receptors, signifying possibilities of future spillover events. No matter the animal subject, Dr. Schountz makes the point of promoting biosafety protections for the animals so as to not endanger or agitate them. Promoting an environment based on sound biosafety and biosecurity will not only soothe the animals, but will also help scientists conduct research safely and securely.

Dr. Steve Higgs (Kansas State University) also conducted transmission and susceptibility experiments at the Kansas State University Biosecurity Research Institute (BRI), which assessed whether SARS-CoV-2-infected mosquitoes can cause vector-borne transmission. This notion is indeed daunting as it alludes to rapid infections of people of all ages and would be particularly burdensome for countries with abundant mosquito populations. Fortunately, results showed that SARS-CoV-2 is not infectious in mosquitoes. This has prompted additional research in animals including swine, cats, and hamsters. Further, BRI has also shown its propensity to initiate scientific experiments in response to current events as they currently study SARS-CoV-2 survivability on different surfaces within meat packing plants after news of COVID-19 outbreaks in such facilities.

Biosafety and Biosecurity as the Avatar for Infectious Disease Preparedness and Response

Each session featured panelists presenting the newest biosafety and biosecurity insights in response to COVID-19-derived challenges in the life sciences. In a time when the pandemic presses on, more strongly in some parts of the world compared to others, the adversities faced so far also served as catalysts for further COVID-19 research and development (R&D), providing opportunities for biosafety and biosecurity to take the reins on guiding institutional change and laboratory operational improvements. What the 2020 ABSA Conference has shown is the mettle, commitment, and initiative necessary to overcome obstacles posed by infectious diseases. As daunting and burdensome as infectious disease are, the scientific community strives to make impactful and positive changes so that we can adapt to an increasing infectious disease threat landscape aggravated by pressures such as globalization, urbanization, and climate change. Developments come at a time when the world can no longer ignore the benefits of promoting biosafety and biosecurity. These disciplines have proven their merit in increasing human and animal protection, and are also presented as lifelines for the healthcare, public health, and scientific communities to change and adapt to a new infectious disease-fused reality that will be essential in enduring and navigating a post-COVID-19 environment.