Stability of Drugs Stored in Helicopters for Use by Emergency Medical Services: A Prospective Observational Study.

STUDY OBJECTIVE: Drugs stored in rescue helicopters may be subject to extreme environmental conditions. The aim of this study was to measure whether drugs stored under the real-life conditions of a Swiss helicopter emergency medical service (HEMS) would retain their potency over the course of 1 year. METHODS: A prospective, longitudinal study measuring the temperature exposure and concentration of drugs stored on 2 rescue helicopters in Switzerland over 1 year. The study drugs included epinephrine, norepinephrine, amiodarone, midazolam, fentanyl, naloxone, rocuronium, etomidate, and ketamine. Temperatures were measured inside the medication storage bags and the crew cabins at 10-minute intervals. Drug stability was measured on a monthly basis over the course of 12 months using high-performance liquid chromatography. The medications were considered stable at a minimum remaining drug concentration of 90% of the label claim. RESULTS: Temperatures ranged from -1.2 °C to 38.1 °C (29.84 °F to 100.58 °F) inside the drug storage bags. Of all the temperature measurements inside the drug storage bags, 37% lay outside the recommended storage conditions. All drugs maintained a concentration above 90% of the label claim. The observation periods for rocuronium and etomidate were shortened to 7 months because of a supply shortage of reference samples. CONCLUSION: Drugs stored under the real-life conditions of Swiss HEMS are subjected to temperatures outside the manufacturer's approved storage requirements. Despite this, all drugs stored under these conditions remained stable throughout our study. Real-life stability testing could be a way to extend drug exchange intervals.

The implementation of cold chain approach at transportation and storage of immunobiological preparations.

In the modern conditions of the coronavirus pandemic, the issue of transportation of immunobiological drugs is particularly actual, since control measures in this direction provide for supply of vaccines to different states, that naturally involves duration of transportation and compliance with certain established temperature regime at all stages of logistics chain, violation of which results in loss of pharmaceutical properties by drugs. The analysis demonstrated that currently transportation of immunobiological drugs is carried out within the framework of cold chain approach, which establishes mandatory compliance with temperature range of storage and transportation. Thus, the most important issue is control of compliance with temperature regime, which requires appropriate technical equipment at all levels of cold chain, ensuring fixation of detected violations.

Ensuring quality and integrity of vaccines throughout the cold chain: the role of temperature monitoring.

INTRODUCTION: Vaccines have continually proven their inestimable value to the world through the eradication of smallpox, gains achieved toward a polio-free world, and controlling other vaccine-preventable diseases. Although vaccines require certain temperatures and conditions to maintain their potency, supply chain controls vary greatly at different legs of the global journey. Vaccine manufacture is closely managed, but inconsistencies plague the cold chain when vaccines are shipped and stored in variable conditions. Monitoring vaccine temperatures throughout the cold chain is of paramount importance to ensure quality. The emerging COVID-19 vaccines present the world with new challenges and additional opportunities to establish best practices for safeguarding human health. AREAS COVERED: We review the risks associated with the vaccine cold chain that require temperature monitoring throughout shipment and storage. Electronic and chemical monitoring devices are compared along with data needs. Regulatory oversight and guidance are also discussed. EXPERT OPINION: Regulatory oversight has contributed to the creation of a risk management and quality culture among private sector players in the vaccine field. Meanwhile, the public sector (the main player at the country level) remains largely untouched by regulatory oversight. Adherence to best practices shall only be possible with increased regulatory oversight of public sector operations.

Presence of unsafe chemical impurities, accelerated evaporation of alcohol, and lack of key labeling requirements are risks and concerns for some alcohol-based hand sanitizers and dispenser practices during the COVID-19 pandemic.

Alcohol-based hand sanitizers (ABHS) have been an important hand hygiene tool during the COVID-19 pandemic. Recently, ABHS from non-traditional drug manufacturers have entered the market, triggered by a lack of ABHS availability. Some of these ABHS contain high levels of chemical impurities that may be harmful with frequent exposure. Additionally, the use of refillable dispensers designed to accept ABHS from bulk containers allows for mixing and evaporation that may compromise ABHS integrity. To understand the risks associated with low quality ABHS and bulk refilling practices, we collected 77 ABHS samples sourced from community settings (restaurants, grocery stores, etc.) and 40 samples from a single school district. All samples were obtained from bulk refillable dispensers that were in use. Samples were analyzed for alcohol content, chemical impurities, aesthetic qualities, and presence of drug labeling information. Additionally, we performed laboratory-based experiments to determine the impact of dispenser design on alcohol evaporation rates. Over 70% of samples for which photos were available showed lack of essential labeling information, including missing "Drug Facts Labels". For ABHS samples acquired from community settings, nearly 14% of samples had visible impurities, and over 30% of samples had concentrations of acetal and acetaldehyde in excess of FDA interim limits. Subpotent ethanol concentrations were observed in 9.09% and 82.05% of samples from community settings and the school district, respectively, with the school district sample results being associated with dispenser misuse. Laboratory-based experiments show dispenser design significantly impacts the rate of ethanol evaporation of ABHS products, especially if stored in open refillable dispensers without an internal reservoir. This study demonstrates risks associated with use of inferior ABHS and bulk refilling practices. Regulatory agencies should issue guidance on best practices in community settings to ensure the integrity of ABHS as an essential public health tool to prevent the spread of COVID-19 and other transmissible diseases.

Thermostable vaccines: an innovative concept in vaccine development.

INTRODUCTION: Vaccines represent he most common and safer ways of combating infectious diseases. Loss of potency owing to thermal denaturation or degradation of almost all the vaccines necessitates their storage, transportation, and final dissemination under refrigerated conditions. However, maintenance of a continuous cold chain raises the costs of vaccines significantly. A large number of life-saving vaccines are discarded before their application owing to exposure to sub-optimum temperatures. Therefore, there is a pressing need for the development of a thermostable vaccine with a long shelf life at ambient temperature. AREAS COVERED: A literature search was performed to compile a list of different vaccines, and their storage and handling conditions. Similarly, a separate list was prepared for different coronavirus vaccines. A literature survey was also performed to look at different approaches undertaken globally to address the issue of the cold-chain problem. We emphasized the importance of yeast cells in the development of thermostable vaccines. In the end, we discussed why thermostable vaccines are required, not only in resource-poor countries but also for resource-rich countries . EXPERT OPINION: Temperature change can severely impact the stability of various life-saving vaccines. Therefore, there is a pressing need for the development of thermostable vaccines with a long shelf lives.

Editorial: First Approval of the Protein-Based Adjuvanted Nuvaxovid (NVX-CoV2373) Novavax Vaccine for SARS-CoV-2 Could Increase Vaccine Uptake and Provide Immune Protection from Viral Variants.

The Nuvaxovid™ (NVX-CoV2373) Novavax vaccine is a recombinant spike (S) protein nanoparticle vaccine combined with the Matrix-M adjuvant. On December 20, 2021, the European Commission of the European Union (EU) granted conditional marketing authorization for the Nuvaxovid™ (NVX-CoV2373) Novavax vaccine, following recommendations from the European Medicines Agency (EMA). On February 3, 2022, this vaccine was granted conditional marketing authorization (CMA) in Great Britain by the Medicines and Healthcare Products Regulatory Agency (MHRA) for use in individuals ≥18 years. The two vaccine components elicit both B-lymphocyte and T-lymphocyte immune responses to the S protein of SARS-CoV-2. The full-length S protein in this vaccine has common epitopes that could protect against all the SARS-CoV-2 viral variants. Also, the vaccine is stable and has a shelf life of 9 months when stored at standard refrigerated temperatures of between 2-8°C. This Editorial aims to present an update on the first approval of a protein-based adjuvanted vaccine for SARS-CoV-2, Nuvaxovid (NVX-CoV2373) from Novavax, and why it is such a significant development at this time.

Exploring Challenges to COVID-19 Vaccination in the Darfur Region of Sudan.

The current COVID-19 pandemic has affected the ability of health systems to provide essential services globally. The Darfur region, located in the western part of Sudan, has been largely devastated by the war that began in 2003 and has been drawing considerable attention from the international community. The war, which erupted as a result of environmental, political, and economic factors, has led to tragic outcomes. Collapsing health-care infrastructures, health workforce shortages, lack of storage facilities for medicines and medical products, and inadequate access to health services are some of the effects of the war. After Sudan received the AstraZeneca COVID-19 vaccine through the COVID-19 Vaccines Global Access facility, significant challenges have been implicated in the delivery, storage, and use of the vaccine in the Darfur region. Lack of vaccine storage and transportation facilities, vaccination hesitancy, inequity in the distribution to health facilities, and shortage of health-care professionals resulting from insecurity and instability have added an extra layer of burden on local authorities and their ability to manage COVID-19 vaccinations in the region adequately. Addressing the impact of COVID-19 requires an effectively managed vaccination program. In the face of current challenges in Darfur, ensuring a fully vaccinated population might remain far-fetched and improbable if meaningful efforts are not put in place by all stakeholders and actors to address some of the challenges identified.

Stability of Captisol-enabled versus propylene glycol-based melphalan at room temperature and after refrigeration.

PURPOSE: To compare the chemical stability of Captisol-enabled (CE) melphalan ("CE-melphalan"; Evomela, Acrotech Biopharma LLC) and propylene glycol (PG)-based melphalan ("PG-melphalan"; Alkeran, GlaxoSmithKline) admixtures prepared with 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags or reconstituted vials stored at room temperature (RT) and under refrigeration. METHODS: Lyophilized CE-melphalan and generic PG-melphalan were reconstituted to 5 mg/mL with 0.9% sodium chloride injection or manufacturer-supplied diluent, respectively. The reconstituted vials were then diluted to the desired concentrations with 0.9% sodium chloride injection in PVC bags and were stored at RT (23oC) or under refrigeration (4oC). Aliquots were withdrawn from the bags and reconstituted vials of CE-melphalan and PG-melphalan immediately after preparation and at predetermined time intervals. Melphalan concentrations were measured using a validated high-performance liquid chromatography method. RESULTS: CE-melphalan reconstituted in PVC bags at concentrations of 1 and 2 mg/mL was stable for 6 and 24 hours, respectively, at RT and for 8 and 24 hours, respectively, at 4oC. PG-melphalan reconstituted in bags at 1, 1.5, and 2 mg/mL was stable for 1, 2, and 2 hours, respectively, at RT and for 2, 4, and 4 hours, respectively, at 4oC. Reconstituted CE-melphalan vials were stable for 48 hours at both RT and 4oC, whereas PG-melphalan vials were stable for 6 hours at RT but formed precipitate within 2 hours at 4oC. CONCLUSION: CE-melphalan remained stable longer than generic PG-melphalan under the test conditions. CE-melphalan at 2 mg/mL has 24-hour stability at RT and can be used for extended infusion times or may be compounded ahead of time. Reconstituted CE-melphalan vials are stable for 48 hours at both RT and 4oC.

Opportunities and Challenges for mRNA Delivery Nanoplatforms.

With the global outbreak of SARS-CoV-2, mRNA vaccines became the first type of COVID-19 vaccines to enter clinical trials because of their facile production, low cost, and relative safety, which initiated great advances in mRNA therapeutic techniques. However, the development of mRNA therapeutic techniques still confronts some challenges. First, in vitro transcribed mRNA molecules can be easily degraded by ribonuclease (RNase), resulting in their low stability. Next, the negative charge of mRNA molecules prevents them from direct cell entry. Therefore, finding efficient and safe delivery technology could be the key issue to improve mRNA therapeutic techniques. In this Perspective, we mainly discuss the problems of the existing mRNA-based delivery nanoplatforms, including safety evaluation, administration routes, and preparation technology. Moreover, we also propose some views on strategies to further improve mRNA delivery technology.

Recommendations for Prevention and Control of Influenza in Children, 2021-2022.

This technical report accompanies the recommendations of the American Academy of Pediatrics for the routine use of the influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2021-2022 season. Influenza vaccination is an important intervention to protect vulnerable populations and reduce the burden of respiratory illnesses during circulation of severe acute respiratory syndrome coronavirus 2, which is expected to continue during this influenza season. In this technical report, we summarize recent influenza seasons, morbidity and mortality in children, vaccine effectiveness, vaccination coverage, and detailed guidance on storage, administration, and implementation. We also provide background on inactivated and live attenuated influenza vaccine recommendations, vaccination during pregnancy and breastfeeding, diagnostic testing, and antiviral medications for treatment and chemoprophylaxis.

Inhalable nanocatchers for SARS-CoV-2 inhibition.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.

Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain.

Development of effective vaccines against coronavirus disease 2019 (COVID-19) is a global imperative. Rapid immunization of the entire human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and different vaccine approaches are being pursued. Engineered filamentous bacteriophage (phage) particles have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans. Herein we report the development and initial evaluation of two targeted phage-based vaccination approaches against SARS-CoV-2: dual ligand peptide-targeted phage and adeno-associated virus/phage (AAVP) particles. For peptide-targeted phage, we performed structure-guided antigen design to select six solvent-exposed epitopes of the SARS-CoV-2 spike (S) protein. One of these epitopes displayed on the major capsid protein pVIII of phage induced a specific and sustained humoral response when injected in mice. These phage were further engineered to simultaneously display the peptide CAKSMGDIVC on the minor capsid protein pIII to enable their transport from the lung epithelium into the systemic circulation. Aerosolization of these "dual-display" phage into the lungs of mice generated a systemic and specific antibody response. In the second approach, targeted AAVP particles were engineered to deliver the entire S protein gene under the control of a constitutive CMV promoter. This induced tissue-specific transgene expression, stimulating a systemic S protein-specific antibody response in mice. With these proof-of-concept preclinical experiments, we show that both targeted phage- and AAVP-based particles serve as robust yet versatile platforms that can promptly yield COVID-19 vaccine prototypes for translational development.

Next-Generation COVID-19 Vaccines Should Take Efficiency of Distribution into Consideration.

The dire need for safe and effective coronavirus disease (COVID-19) vaccines is met with many vaccine candidates being evaluated in pre-clinical and clinical studies. The COVID-19 vaccine candidates currently in phase 3 or phase 2/3 clinical trials as well as those that recently received emergency use authorization (EUA) from the United States Food and Drug Administration (FDA) and/or other regulatory agencies worldwide require either cold (i.e., 2-8°C) or even freezing temperatures as low as -70°C for storage and distribution. Thus, existing cold chain will struggle to support both the standard national immunization programs and COVID-19 vaccination. The requirement for cold chain is now a major challenge towards worldwide rapid mass vaccination against COVID-19. In this commentary, we stress that thermostabilizing technologies are available to enable cold chain-free vaccine storage and distribution, as well as potential needle-free vaccination. Significant efforts on thermostabilizing technologies must now be applied on next-generation COVID-19 vaccines for more cost-effective worldwide mass vaccination and COVID-19 eradication.

Whole blood stability evaluation of monoclonal antibody therapeutics using volumetric absorptive microsampling.

Volumetric absorptive microsampling (VAMS) is increasingly utilized for both nonclinical and clinical pharmacokinetic studies. Currently, VAMS is employed as the sampling method for the detection of antibodies for coronavirus disease 2019. Biotherapeutics whole blood stability on VAMS presents as a critical concern for the health and pharmaceutical industries. In this follow-up to our previous publication, we evaluated daclizumab and trastuzumab whole blood sample stability on VAMS. The drug recovery data we observed at room temperature for short term and -80°C for long term was very encouraging. The knowledge could help us better understand and plan important investigation timelines, especially pandemic situations where human whole blood samples from a large population are collected and in urgent need of data analysis.

COVID-19 vaccines and vaccine administration.

This article provides an overview of current COVID-19 vaccines available within the UK, including their mode of action, storage and handling. It outlines the recommendations on priority groups for vaccination and provides insight into the training recommendations for vaccinators.