Abstract
Background:
The AIDS and Cancer Specimen Resource (ACSR) is a network of four regional biospecimen repositories and a technical core in the United States and South Africa. Its mission is to acquire, store, and distribute HIV-associated malignancy specimens and related clinical data to support translational research. At the outset of the COVID-19 pandemic, it became apparent that existing ACSR Standard Operating Procedures (SOPs) were not sufficient to ensure long-term maintenance and integrity of inventories during periods of extended shutdown. The ACSR needed an administrative SOP for situations pertaining to epidemics/pandemics. The ACSR Quality Working Group (QWG), comprised of representatives from each of the five ACSR sites and an external member who directs a large university medical center biorepository, addressed the issue.
Methods:
To understand the individual problems the sites faced, questions were developed to query each of the six QWG sites' contingency plans to cover this type of emergency, the amount of work allowed onsite and by whom, the challenges sites experienced, and the lessons learned to assist with future similar situations, while remaining consistent with the existing IRB protocols.
Results:
Reported challenges spanned all activities of classical biobanks and differed within the geographical locations of the sites and the local COVID-19 infection rate. Review of the responses to the questions revealed that the general shutdown of society external to the biorepositories presented them with a homogeneous collection of problems, limitations, and needs. This led to creating an SOP that addresses planning for pandemic emergencies, scaling down of activities, shutting down, and reopening plans.
Conclusions:
The ACSR QWG sites now have a structured response SOP for their sites, including guidance on how to develop and implement an emergency shutdown and reopening plan. The complete SOP is publicly available on the ACSR website.
Introduction
Most biobanks operating under Best Practices from either the National Cancer Institute (NCI), 1 the International Society for Biological and Environmental Repositories (ISBER),2–4 or the Organization for Economic Cooperation and Development (OECD) 5 have emergency and contingency plans for natural emergencies, such as earthquakes and floods, or other emergencies, including power outages, laboratory hazard injuries, spills, and fires. Biorepository managers and directors may benefit from having Standard Operating Procedures (SOPs) for handling these local emergencies, and personnel should be knowledgeable with the plans through training, continuing education, accreditation, certification programs, and standards.6–10 In addition, institutional risk management exists to mitigate these occurrences. In these situations, shutdowns may last hours or a few days, but not months or over a year as we are experiencing due to an infectious agent such as SARS-CoV-2.11,12
The early weeks of this pandemic stressed contingency plans of biobanks. Unforeseen pressures compelled hurried adjustments and accommodations while dealing with what was seen as a life-threatening situation, and there was fear among biobanking personnel to come to work. 13 Worldwide, the COVID-19 pandemic caused the shutdown of not only biobanks, but almost every service supply chain and even country borders.
Biobanks in academic institutions faced the challenge of ensuring continuation of essential services in an environment that was closing down rapidly. Many biobanks in research facilities dealt with a total shutdown of research programs, 14 while others maintained only the bare minimum staff. Despite this, biobanks needed to ensure the continued operation and monitoring of their cold storage units and specimens. 15 Biobank directors, like others responsible for a critical service, were suddenly navigating new situations, needing to identify who and what was considered “essential,” establishing continued functions and operations and making difficult decisions.16,17
The AIDS and Cancer Specimen Resource (ACSR), 18 funded by the National Cancer Institute (NCI), is a multisite consortium with collaborating biospecimen repositories and a technical core in the United States (Washington D.C., San Francisco, CA., Houston, TX., Scottsdale, AZ) and South Africa (Cape Town). 19 Four of the ACSR sites are university medical center biorepositories and one is a hospital-based biorepository. The ACSR's mission is to acquire, store, and equitably distribute, at no charge, tissues, biological fluids, and clinical data from individuals with HIV-associated malignancies with the overall goal to improve cancer prevention and treatment. The ACSR is governed by its Executive Committee (EC), which is composed of members from each of its sites and the NCI. The ACSR Quality Working Group (QWG) comprises representatives from each of the five ACSR sites and an external member who directs a large university medical center biorepository in Tucson, Arizona, associated with the ACSR and also funded by the NCI. The QWG provides guidance for the six QWG sites on the quality maintenance of functions and operations and oversees the ACSR SOPs. Final drafts, approved by the EC, are made publicly available. Each ACSR site's biobanking operations are managed locally in accordance with its home institution and local jurisdiction with reliance on a central Institutional Review Board (IRB) protocol. Specimens and data procured toward the ACSR mission are entered into a laboratory inventory database at each site and investigators request materials through a formal ACSR application process.
At the onset of COVID-19 existing ACSR-approved SOPs did not adequately cover pandemic events. To harmonize and standardize the response of ACSR QWG sites for the ongoing COVID-19 pandemic and to inform any future emergency situations, the ACSR QWG decided that an emergency response SOP was needed to guide the six QWG sites. We describe the process used by the ACSR QWG to extract information from this experience and produce a guiding SOP in the event of future shutdowns of this magnitude.
Methods
A subcommittee of QWG members produced a set of questions to circulate among their six biorepository sites. The purpose of the questions was to gather information about the status of the sites in relation to the pandemic shutdown by eliciting free-text responses. The QWG reviewed and discussed the responses from the six QWG sites and drafted an SOP. Once completed, the QWG chair submitted the draft SOP to the EC for review. After finalization of suggested revisions, the EC approved the SOP, which was added to the existing approved ACSR SOP portfolio. The new approved SOP remained consistent with the IRB protocol.
Results
Questions and summary of responses
In this study, we provide the questions and a summary of responses from the six biorepositories represented by the QWG.
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While the ACSR and individual biorepositories had extensive emergency plans, mostly dealing with local events, none had emergency plans that covered pandemics of the magnitude of COVID-19, and developed plans “on the fly.”
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The Technical Core at the nonacademic hospital site with a low COVID-19 incidence reported that there were no reductions in staff and they were permitted to continue to work. Its personnel were still able to do their jobs, and as a technical core, they continued to have the ability to produce ACSR work, such as production of tissue microarrays and fulfillment of other distribution requests if there was ability for the requester to receive them. The South African site reported that all personnel were required to work from home, and permits for traveling to work were required to accomplish essential services at the biorepository.
Biorepository directors had to stringently express their need to be on campus for certain activities during the shutdown. Personnel at some sites were only allowed on the premises if a freezer alarmed; therefore, they needed to take such steps as ensuring biobank personnel were considered “essential personnel” by institutional administration so that occasional visits to the laboratory to make visual checks on specimen and equipment were permitted. This included naming each person and the specific task to be performed.
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In essence, no prospective samples were being gathered during the entire shutdown since collecting sites had also shut down. For example, at most academic medical center sites, clinics were closed and only emergency surgeries were performed.
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All sites with liquid nitrogen storage faced issues because of the restrictions to both laboratory staff as well as vendors. The sites with an institutional cryogenic core were provided with back-up plans to deliver liquid nitrogen tanks. Liquid nitrogen level checks and scheduling tank switch-outs became a vital and challenging activity. The South African site also had to take the added backup measure to manually fill liquid nitrogen freezers, due to possible interrupted delivery of portable cryogenic containers; fortunately, they were able to access a bulk liquid nitrogen tank. Additionally, a prolonged shortage of dry ice ensued at the South African site due to a nationwide shortage of CO2.
Immediately before the onset of shutdown, some specimens were already shipped and could not be stopped, resulting in delays and impacting specimen viability.
South Africa implemented a COVID-19 Risk-Adjusted Strategy that differentiated between five restriction levels, with alert level 5 being the highest (equating to a hard lockdown) and level 1 being the lowest (less restrictive). 20 Distributions to international researchers were ceased at the South African site and only resumed when restrictions were lifted and export permits could be obtained.
Institutional requirements varied at different institutions and hospitals. Some university Ethics Committees suspended all human subject research and trials, except those involving treatment/intervention. Research coordinators who had interactions with patients and hospital staff had to be trained on proper hygiene, donning and doffing personal protective equipment (PPE), as well as sanitation measures required for interactions with patients.
A big challenge for ACSR biorepository directors was to find engaging and important work for staff to do remotely. Although accustomed to handling specimens in a biobank, at home, all work was shifted to data entry, data clean-up, and review of SOPs and other administrative documents. The specimen databases were reviewed, and thorough quality checks were performed.
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We learned that personnel schedules, including backup rosters, were important in case staff or their family members became ill or were required to quarantine due to possible exposures. ACSR biorepository directors needed to be sensitive to home life issues of their staff members, including childcare, COVID-19 illnesses of family members, and the psychological challenges associated with prolonged isolation and fear of infection. The safety and wellbeing of staff was the highest priority.
Communication channels with biorepository staff, institutional risk management, and research leadership had to be established and maintained. Because the biobanking staff were working remotely for several months, remote communication and video meetings replaced in-person meetings. Communication through email was critical to keeping everyone working and being productive. The ACSR needed to put communication procedures in place delineating the path each ACSR site should take to ensure that other sites and the ACSR EC can be kept aware of their operational status, closing, and opening situations.
Another challenge was to gain remote access to institutional servers housing biorepository data, since working with hard copy data offsite was not routine and would require special security measures and considerations. At one site, institutional policies and firewalls did not allow biobanking personnel to remotely access data on institutional servers. This restriction made working offsite impossible until such permissions were established. As a result, remote access to institutional servers needed to be requested on a permanent basis for all staff to alleviate any delay if remote access becomes necessary in the future.
Formal action taken
The reported challenges spanned all activities of a traditional biobank's workflow. There was a wide range of responses revealing the need for an SOP to cover such emergencies. The procedures proposed by the QWG and adopted by the EC encompassed general planning for emergencies, scaling down of activities, shutdown plan, and resumption of activities/return of personnel to work as follows:
General Planning for Emergencies
List tasks that can be done remotely such as repurposing biobank activities.
Confirm who will be permitted to come to the site location.
Determine who has the skills to perform necessary tasks.
Update rosters for freezer response and other emergencies.
Define scope of work during shutdown, such as data clean-up activities or review of SOPs.
Plan for illness in team members (back-up plan).
Test systems for remote access to secure servers.
Review these plans annually.
Scaling Down of Activities
Follow local/national and institutional instructions for continuation of work.
Define the capacity of staff to work and the scope of work.
Identify all critical activities that can be ramped down, curtailed, suspended, or delayed.
Identify primary and backup personnel permitted to safely perform essential activities and confirm access to all areas.
Ensure the contact list of biorepository personnel, principal investigator, and biorepository administrative director is up to date.
Cancel shipping of research materials that have not been sent. If shipping is permitted by local regulations, make arrangements for centralized receiving and temporary storage or redirect shipments to another site if possible.
Contact loading dock/mail services personnel to notify them of any expected incoming shipments.
Set up routine delivery of liquid nitrogen to prevent loss of frozen materials and follow-up with suppliers to ensure delivery.
Confirm call lists for emergency alarms are current and in effect.
Dispose of biological waste, chemical waste, and sharps. Properly store all chemicals. Remove clutter from benchtops and chemical hoods. Thoroughly, disinfect biosafety cabinets.
Notify the ACSR EC of a shutdown (responsibility of biorepository director).
Notify all sites of another site's closing or its specific situation (responsibility of the EC chair).
Shutdown Plan
Designate useful tasks and responsibilities to work on from the offsite location.
Determine work schedules.
Develop a communication plan between director, team members, and other ACSR sites.
Plan for alternative work should internet connectivity or hardware not be available.
Provide support for staff (e.g., mental health support or ergonomic awareness).
Ensure security of HIPAA-protected documents and access to institutional systems.
Ensure required hardware and software are installed and can be accessed remotely.
Confirm that internet access is available at the remote location.
Evaluate whether appropriate security is maintained while working remotely.
Ensure that IT support is accessible when working remotely.
Ensure the ability to access databases and records on secure servers.
Resumption of Activities – Return to Work
Resume work under direction from institution as aligned with local/national regulations.
Define systems and materials required to resume biobank activities.
Define any changes to Universal Precautions (PPE, sample handling, storage).
Comply with regulatory guidance for direct patient contact.
Notify the EC when activities resume (responsibility of the site director).
Discussion
The goal of this work was to develop a common SOP for emergency shutdown and reopening based on qualitative information from six sites in the ACSR network. The strength of this work was the diversity of the source of responses since the members of the QWG represent biobanks situated in university medical centers as well as a biobank embedded in a nonacademic hospital, and in addition these are located in the United States and South Africa. Although there were differences in the rules for in-person attendance in the physical biorepositories, there was a general shutdown of society surrounding the biorepositories, hospitals were being overwhelmed with COVID-19, transportation was at a standstill, people were fearful, and other external enterprises were stopping work. The slow-down or absence of sample generation and difficulties with shipping, delivery, liquid nitrogen, and remote access, were largely the same for all biorepositories. These externalities presented the biorepositories with a predominantly homogeneous collection of problems, limitations, and needs. Therefore, the SOP developed by the QWG was applicable across the spectrum of the ACSR and the QWG enterprise.
As a multisite, classical biobank, the ACSR needed to ensure long-term maintenance and integrity of its inventories during a lengthy shutdown while ensuring compliance with both local governmental and institutional restrictions. The QWG engaged in self-examination and formulation of operating procedures to address the situation. Given the urgency of the situation and the enormous task, the biorepository directors demonstrated leadership within their organizations and all of the biobanking sites were able to safely shut down, maintain equipment, and preserve specimens.
The focus of the current work was on developing a standard procedure for shutting down and reopening ACSR network operations in the case of an emergency. Other issues important to emergency planning include financial contingencies and policies related to stakeholders and funding agencies, budget questions regarding reduced in-person activities, supplies, and travel expense, as well as the need to monitor disease surveillance and the development of early warning or alert systems. Furthermore, coordination with host institutions on risk assessment, risk management, and advance planning for future emergencies are also important. These issues need to be considered as part of a broader emergency preparedness plan.
Realizing the enormity of logistics involved in its usual operations and functions, the administrative SOP developed by the ACSR QWG strives to provide guidance on defining and implementing the minimum necessary components to ensure (1) the continued viability and integrity of the specimen inventory, (2) ability of site personnel to function remotely, and (3) timely communications with users of the facilities for awareness of the situation. The Emergency Shutdown and Reopening Plan SOP is a guide to all ACSR personnel and the EC, but does not supersede the respective local, national, and institutional regulations and guidelines. The complete SOP is publicly available at the ACSR website under Resources. Although this is a small network of biorepositories, our experience during this pandemic and the Emergency Shutdown and Reopening SOP produced may be of value to the biorepository community.
Footnotes
Author Disclosure Statement
No conflicting financial interests exist.
Funding Information
National Cancer Institute (Grant No. UM1CA181255).