The test, treat, and track strategy is critical to containing the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this strategy is to contain the virus by quickly identifying both symptomatic and asymptomatic patients, performing contact tracing, and quarantining patients to reduce transmission.
From the pandemic’s onset, testing has been limited by supply chain problems at all levels. The unprecedented worldwide demand for viral diagnostic testing (ie, PCR tests) resulted in critical shortages of key supplies, including flocked nylon swabs for collecting samples and viral transport media (VTM) used for preserving and transporting samples. In response, vendors around the world attempted to quickly scale up manufacturing, but these efforts initially stumbled due to international lockdowns, fluctuating labor pools, and transport system delays.
As part of the response, the United States Food and Drug Administration began granting emergency use authorizations (EUAs) to allow unapproved diagnostic tests and related supplies to enter the market, and relaxing regulations that allow for expanded production and more timely distribution of previously approved products.1 One example of an affected product type was VTM, which is regulated by the FDA as a medical device due to its role in disease diagnosis. In January 2020, the FDA sought to increase production capacity by allowing manufacturers to sell VTM without submitting a 90-day pre-market notification, which includes evidence of equivalence to an existing, legally marketed device. In addition, the FDA issued guidance to temporarily allow CLIA-certified laboratories to produce VTM for in-house COVID-19 diagnostic testing.2 This latter exemption enabled our hospital facilities to establish and maintain our own VTM production through collaboration between the laboratory and the pharmacy.
The Role of VTM in COVID-19 Testing
As with most infectious diseases, the three key phases involved in viral diagnostic testing are sample collection and transport (pre-analytical), test execution (analytical), and results reporting/contact tracing (post-analytical). Sample collection and transportation is dictated by the type of testing and thus far, the most common and reliable COVID-19 diagnostic test is a laboratory-based assay that detects viral nucleic acid through amplification of a SARS-CoV-2 specific sequence; eg, reverse transcription PCR (RT-PCR).
Given that SARS-CoV-2 is composed of RNA that is extremely unstable and degrades easily,3 storing samples in the wrong environmental conditions can lead to false negative results, as can sample contamination by enzymes or other microorganisms that break down RNA. For these reasons, the CDC considers “proper collection [and storage] of specimens [as] the most important step in the laboratory diagnosis” of COVID-19.2
Sample collection for this type of testing starts with a sterile swab tipped with a synthetic material to collect secretions from either the patient’s nasopharynx (most common), oropharynx, nasal mid-turbinate, and/or anterior nares (see FIGURE 1). Swabs are ideally “flocked” by electrostatic insertion of pin-like filaments into the swab head, rather than by winding fibers around a shaft, for improved pickup and release of sample. Note that swabs with wooden shafts, cotton tips, and/or containing calcium alginate are not appropriate as they contain genetic material that interferes with diagnostic tests; only a small subset of available swab inventory is appropriate for viral testing. Collected swabs are then placed in a sterile collection tube and stored at either 2-8°C or -70°C, depending on whether the sample can be tested within 72 hours.2
The VTM is housed within each sterile collection tube and each swab is broken at a score point to allow the head of the swab to fit into the tube (see FIGURE 2). As transport media is designed to be an optimal environment for preserving the viability of the target analyte during transportation and storage, the gold standard is VTM (also referred to as universal transport media).2
VTM is preferred as it is a non-hazardous mixture of buffered solutions and antimicrobials that preserves the virus while eliminating contaminant flora that might interfere with testing. It has proven compatibility with a wide variety of clinical tests from PCR to direct antigen testing to culturing, allowing different tests to be run from the same sample (see FIGURE 3).4
Due to VTM shortages throughout the pandemic, the FDA and CDC have recommended using alternative media, including sterile saline, liquid Amies, and inactivating transport media.2 However, these options do not have the same versatility, stabilizing, and inhibitory properties as VTM. Inactivating transport media is the least desirable as it contains hazardous chemicals that can release toxic cyanide gas when mixed with acids such as bleach, a commonly utilized disinfecting agent for eliminating stray contaminant nucleic acids.5,6
Ingredients in VTM
As a device designed to maintain the viability and virulence of collected samples, VTM has been optimized for decades, initially to preserve viability for cultures, and later to facilitate nucleic acid-based testing. Commonly, VTM is composed of fetal bovine serum (FBS), Hanks’ Balanced Salt Solution (HBSS), antibiotics and antifungals, as well as phenol red.7 However, a multitude of recipe variations exist to cater to the interactions between sample collection devices (ie, swab) in media solutions, plastic in storage containers, and variability of freeze/thaw cycles.
While the ingredients used to produce VTM are commonplace in both clinical and research laboratories, within a health system, other clinical disciplines that may be charged with producing or providing a medical device such as VTM (ie, the pharmacy), may find the ingredients somewhat foreign. As a reminder, the purpose and safety of each VTM ingredient is described below.
Commercially, FBS comes in two forms: heat inactivated and not inactivated. Traditionally, most protocols for making VTM include heat inactivation as a necessary step in preparation. This is to rid the serum of any complement proteins that inadvertently eliminate foreign organisms (eg, viruses). The utility of heat inactivation is debated, as some experts consider the complement factors present to be negligible. With a lack of definitive evidence, heat inactivation is a conservative approach, especially given the low cost and technical skill needed.
Note that your pharmacy colleagues may be uncomfortable handling FBS as it is a serum-supplement. However, FBS does not present any health, physical, or environmental hazards. Additionally, no hazard statements or precautionary statements (ie, prevention, response, storage, disposal) are applicable to FBS.9
Vital Role of the Lab
The University of Iowa Health Care (UIHC) is a non-profit academic medical system that includes 811 beds within two tertiary care hospitals: UI Hospitals and Clinics and UI Stead Family Children’s Hospital. UIHC has been able to meet the increased demand for COVID-19 testing without interruption due in part to the onsite production of VTM. Although the production/compounding of VTM may take place in the pharmacy (presuming, for example, the pharmacy is appropriately staffed and has regular access to ISO-certified primary engineering controls), the role of the laboratory in facilitating and validating VTM is essential.
The FDA recommends that CLIA-certified laboratories follow the CDC’s standard operating procedure entitled Preparation of Viral Transport Media if they choose to compound and validate VTM during a supply shortage.12 In this process, the laboratory may be tasked with providing the sterile reagents required for VTM production. Other supplies and materials that may be sourced from the pathology or laboratory departments include serological pipettors and pipet aids, individually wrapped sterile pipets, sterile conical tubes, filter assemblies, labels, and disinfectants. Equipment that may be utilized include vacuum pumps, water baths, refrigeration space, and incubators. These items should be supplied with information and instruction from proper laboratory personnel for effective use.
Lastly, laboratory and pathology can enable appropriate quality assurance checks, including culture-based sterility tests in the microbiology laboratory. The CDC has further guidance on its standard operating procedures for sterility and quality checks.13
When CLIA-certified laboratories and pharmacy departments collaborate to solve challenging issues facing health care practice, the facility as a whole—and the patient—benefits. At UIHC, our willingness to collectively face the shortage of VTM was just one example of how interdisciplinary work can enable quality patient care. Without onsite VTM production, UIHC’s testing capacity would have been exceeded early on in the pandemic, resulting in substantial testing delays. As the global supply chain of VTM normalizes, onsite production of VTM will no longer be relied upon as a primary source at UIHC. However, the rise of COVID-19 has taught us that in today’s unpredictable world, hospitals must have a back-up plan in place that can be quickly activated and scaled when demand for testing increases and supply chain failures occur.
For a more expanded version of this article intended for pharmacy management, which includes UIHC’s Master Formulation Record for compounding VTM, please visit pppmag.com/covid19
Note: See the CDC SOP #DSR-052-05, Preparation of Viral Transport Medium, prior to compounding VTM. Be sure to check the CDC website regularly for updates. For more information, visit: cdc.gov/csels/dls/locs/2020/new_sop_for_creating_vtm.html
Bradley Ford, MD, PhD, is the medical director of the clinical microbiology laboratory for the University of Iowa Hospital and Clinics in Iowa City, Iowa. He earned his MD and PhD from Stony Brook School of Medicine. His research focuses on optimizing clinical diagnostics using a variety of next-generation microbiology platforms.
Felix Lam, PharmD, MBA, BCPS, is the pediatric pharmacy operations manager for University of Iowa Health Care (UIHC) in Iowa City. He earned his PharmD from the University of North Carolina Eshelman School of Pharmacy and his MBA with an emphasis on health care management from the Johns Hopkins Carey Business School while completing a combined PGY1/PGY2 in health system pharmacy administration at The Johns Hopkins Hospital.
Jonathan Wilson, PharmD, MHA, BCPS, BCSCP, is an adult pharmacy operations manager for UIHC. He earned his PharmD from the University of Minnesota College of Pharmacy. Jonathan completed his MHA at the University of Iowa College of Public Health while completing a combined PGY1/PGY2 in health system pharmacy administration at UIHC.
Majd Moubarak, BS, is a pharmacy technician for the University of Iowa Stead Family Children’s Hospital. She completed her BS in plant biology from the University of Iowa. She is actively pursuing national pharmacy technician certification.
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