Development of a multivariate model with desirability-based optimization for simultaneous determination of five co-administrated drugs for the management of COVID-19 infection in their dosage forms via validated RP-HPLC method

More than 2.9 million people have died as a result of the global demographic impact of the coronavirus illness of 2019 (COVID-19). Numerous antiviral and anti-inflammatory medications have FDA approval to treat COVID-19 patients. For the simultaneous determination of COVID-19 utilized medications (Remdesivir, Moxifloxacin, Dexamethasone, Apixaban, and paracetamol) in their dosage forms, a sensitive technique has been developed and validated. The aforementioned medications were separated and quantified with the help of experimental design. The Box-Behnken design was used in the experiment to optimize the chromatographic method's analytical parameters. It employed RP-HPLC with a UV detector. An INERTSIL ODS-3 C18 column (5 µm, 250 × 4.6 mm) with mobile phase composed of acetonitrile: 30 mmoL potassium dihydrogen phosphate buffer (pH = 7.5) (50:50, v/v), at room temperature was employed to separate the aforementioned drugs. Paracetamol was linear over the concentration range (1–50 µg/mL), Moxifloxacin (5–70 µg/mL), Apixaban (5–70 µg/mL), Dexamethasone (1–100 µg/mL), and Remdesivir (5–100 µg/mL). According to ICH guidelines, the new approach underwent thorough validation. Between the proposed method's results and those from the reference or reported methods, there was no significant difference. The technique is simple to use in research of the cited medications in their dosage forms for quality control aspects.

Introducing a New Concept for Value-Driven Acceleration in Biopharma Development

This opinion paper seeks to introduce a disruptive model to accelerate product and process development in the biopharmaceutical industry, especially for vaccines. This model is based on the minimum valuable product and process (MVaP&P), a new concept that allows for adaptation and acceleration, which would enable agility in the way biopharmaceuticals are developed. This article discusses how the MVaP&P approach would make it is possible to discipline and structure biopharmaceutical development to achieve a phase-appropriate and strategy-aligned product in the fastest time possible.Copyright © 2022, UBM Medica Healthcare Publications. All rights reserved.

Development of an ELISA Assay for the Determination of SARS-CoV-2 Protein Subunit Vaccine Antigen Content.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein subunit vaccine is one of the mainstream technology platforms for the development of COVID-19 vaccines, and most R&D units use the receptor-binding domain (RBD) or spike (S) protein as the main target antigen. The complexity of vaccine design, sequence, and expression systems makes it urgent to establish common antigen assays to facilitate vaccine development. In this study, we report the development of a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) to determine the antigen content of SARS-CoV-2 protein subunit vaccines based on the United States Pharmacopeia <1220> and ICH (international conference on harmonization) Q14 and Q2 (R2) requirements. A monoclonal antibody (mAb), 20D8, was identified as the detection antibody based on its high RBD binding activity (EC50 = 8.4 ng/mL), broad-spectrum anti-variant neutralizing activity (EC50: 2.7−9.8 ng/mL for pseudovirus and EC50: 9.6−127 ng/mL for authentic virus), good in vivo protection, and a recognized linear RBD epitope (369−379 aa). A porcine anti-RBD polyclonal antibody was selected as the coating antibody. Assay performance met the requirements of the analytical target profile with an accuracy and precision of ≥90% and adequate specificity. Within the specification range of 70−143%, the method capability index was >0.96; the misjudgment probability was <0.39%. The method successfully detected SARS-CoV-2 protein subunit vaccine antigens (RBD or S protein sequences in Alpha, Beta, Gamma, or Delta variants) obtained from five different manufacturers. Thus, we present a new robust, reliable, and general method for measuring the antigenic content of SARS-CoV-2 protein subunit vaccines. In addition to currently marketed and emergency vaccines, it is suitable for vaccines in development containing antigens derived from pre-Omicron mutant strains.

Development of a multivariate model with desirability-based optimization for simultaneous determination of five co-administrated drugs for the management of COVID-19 infection in their dosage forms via validated RP-HPLC method

More than 2.9 million people have died as a result of the global demographic impact of the coronavirus illness of 2019 (COVID-19). Numerous antiviral and anti-inflammatory medications have FDA approval to treat COVID-19 patients. For the simultaneous determination of COVID-19 utilized medications (Remdesivir, Moxifloxacin, Dexamethasone, Apixaban, and paracetamol) in their dosage forms, a sensitive technique has been developed and validated. The aforementioned medications were separated and quantified with the help of experimental design. The Box-Behnken design was used in the experiment to optimize the chromatographic method's analytical parameters. It employed RP-HPLC with a UV detector. An INERTSIL ODS-3 C18 column (5 µm, 250 × 4.6 mm) with mobile phase composed of acetonitrile: 30 mmoL potassium dihydrogen phosphate buffer (pH = 7.5) (50:50, v/v), at room temperature was employed to separate the aforementioned drugs. Paracetamol was linear over the concentration range (1–50 µg/mL), Moxifloxacin (5–70 µg/mL), Apixaban (5–70 µg/mL), Dexamethasone (1–100 µg/mL), and Remdesivir (5–100 µg/mL). According to ICH guidelines, the new approach underwent thorough validation. Between the proposed method's results and those from the reference or reported methods, there was no significant difference. The technique is simple to use in research of the cited medications in their dosage forms for quality control aspects. [ FROM AUTHOR]

Development and Validation of RP-HPLC Method for Estimation of Favipiravir API and It's Tablet Dosage Form Using Quality by Design Approach

Favipiravir is a pyrazine carboxamide derivative discovered by Toyama chemical of Japan to act against many RNA viruses (potent broad spectrum inhibitor of Influenza & other RNA viruses). The present study gives the development of the RP HPLC method by using Quality by Design followed by validation of developed method for estimation co Favipiravir in bulk and tablet dosage form. The central composite method was applied on organic Phase concentration & buffer PH for initial Screening studies. The selection of optimum chromatographic condition was carried out by design space numerical, graphical optimization on retention time, Peak asymmetry & Theoretical Plates. Optimized analytical method consisted Acetonitrile: water (80:20%v/v) as mobile phase, pH 5, flow rate 1ml/min, a wavelength 323 nm. Favipiravir was eluted with retention time 2.7 min & peak area 51248, Favipiravir showed good linear relationship in range of 10-90 microg/ml with a correlation coefficient of 0.9985. The % RSD for intraday, inter day precision & Repeatability was found to be 0.88, 0.65 & 0.97 respectively. Limit of detection & quantification was found to be 104.44 microg/ml &. 316.5 microg/ml. The method validation parameters were in the prescribed limit as per ICH guidelines. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Can quality management drive evidence generation?

Recent guidance documents from international regulators emphasize the importance of thoughtful trial design and risk-based oversight in delivering reliable results. In practice, these recommendations are often implemented in a fragmented manner, reducing their effectiveness. We argue that collaborative, cross-stakeholder engagement that prioritizes both optimal trial design and tailored oversight are a necessary and effective approach to modernize quality management. This practice is at the core of Quality by Design, an approach that involves identifying important errors that could undermine trial credibility or participant safety and addressing them proactively. While Quality by Design is well suited for clinical trials supporting regulatory approval of a new medicinal product, we describe how the approach is equally relevant for pragmatic trials, including those conducted in the context of a pandemic.

Expanding Quality by Design Principles to Support 3D Printed Medical Device Development Following the Renewed Regulatory Framework in Europe.

The vast scope of 3D printing has ignited the production of tailored medical device (MD) development and catalyzed a paradigm shift in the health-care industry, particularly following the COVID pandemic. This review aims to provide an update on the current progress and emerging opportunities for additive manufacturing following the introduction of the new medical device regulation (MDR) within the EU. The advent of early-phase implementation of the Quality by Design (QbD) quality management framework in MD development is a focal point. The application of a regulatory supported QbD concept will ensure successful MD development, as well as pointing out the current challenges of 3D bioprinting. Utilizing a QbD scientific and risk-management approach ensures the acceleration of MD development in a more targeted way by building in all stakeholders' expectations, namely those of the patients, the biomedical industry, and regulatory bodies.

Stabilizing vaccines via drying: Quality by design considerations.

Pandemics and epidemics are continually challenging human beings' health and imposing major stresses on the societies particularly over the last few decades, when their frequency has increased significantly. Protecting humans from multiple diseases is best achieved through vaccination. However, vaccines thermal instability has always been a hurdle in their widespread application, especially in less developed countries. Furthermore, insufficient vaccine processing capacity is also a major challenge for global vaccination programs. Continuous drying of vaccine formulations is one of the potential solutions to these challenges. This review highlights the challenges on implementing the continuous drying techniques for drying vaccines. The conventional drying methods, emerging technologies and their adaptation by biopharmaceutical industry are investigated considering the patented technologies for drying of vaccines. Moreover, the current progress in applying Quality by Design (QbD) in each of the drying techniques considering the critical quality attributes (CQAs), critical process parameters (CPPs) are comprehensively reviewed. An expert advice is presented on the required actions to be taken within the biopharmaceutical industry to move towards continuous stabilization of vaccines in the realm of QbD.

Optimization of a mAb production process with regard to robustness and product quality using quality by design principles.

Quality by Design principles are well described and widely used in biopharmaceutical industry. The characterization of a monoclonal antibody (mAb) production process is crucial for novel process development and control. Yet, the application throughout the entire upstream process was rarely demonstrated. Following previously published research, this study marks the second step toward a complete process characterization and is focused on the effect of critical process parameters on the antibody production efficiency and quality of the process. In order to conduct the complex Design of Experiments approach with optimal control and comparability, the ambr®15 micro bioreactor platform was used. Investigated parameters included the pH and dissolved oxygen set points, the initial viable cell density (iVCD) as well as the N-1 duration. Various quality attributes (e.g., growth rate, viability, mAb titer, and peak proportion) were monitored and analyzed using multivariate data analysis to evaluate the parameter effects. The pH set point and the initial VCD were identified as key process parameters with strong influence on the cell growth as well as the mAb production and its proportion to the total protein concentration. For optimization and improvement in robustness of these quality attributes the pH must be increased to 7.2, while the iVCD must be lowered to 0.2 × 106 cells/mL. Based on the defined design space, additional experiments verified the results and confirmed the intact bioactivity of the antibody. Thereby, process control strategies could be tuned toward high cell maintenance and mAb production, which enable optimal downstream processing.

Development of Nafamostat Mesylate Immediate-Release Tablet by Drug Repositioning Using Quality-by-Design Approach.

We aimed to develop nafamostat mesylate immediate-release tablets for the treatment of COVID-19 through drug repositioning studies of nafamostat mesylate injection. Nafamostat mesylate is a serine protease inhibitor known to inhibit the activity of the transmembrane protease, serine 2 enzyme that affects the penetration of the COVID-19 virus, thereby preventing the binding of the angiotensin-converting enzyme 2 receptor in vivo and the spike protein of the COVID-19 virus. The formulation was selected through a stability study after manufacturing by a wet granulation process and a direct tableting process to develop a stable nafamostat mesylate immediate-release tablet. Formulation issues for the selected processes were addressed using the design of experiments and quality-by-design approaches. The dissolution rate of the developed tablet was confirmed to be >90% within 30 min in the four major dissolutions, except in the pH 6.8 dissolution medium. Additionally, an in vivo pharmacokinetic study was performed in monkeys, and the pharmacokinetic profiles of nafamostat injections, oral solutions, and tablets were compared. The half-life during oral administration was confirmed to be significantly longer than the reported literature value of 8 min, and the bioavailability of the tablet was approximately 25% higher than that of the oral solution.

Upstream cell culture process characterization and in-process control strategy development at pandemic speed.

As of early 2022, the coronavirus disease 2019 (COVID-19) pandemic remains a substantial global health concern. Different treatments for COVID-19, such as anti-COVID-19 neutralizing monoclonal antibodies (mAbs), have been developed under tight timelines. Not only mAb product and clinical development but also chemistry, manufacturing, and controls (CMC) process development at pandemic speed are required to address this highly unmet patient need. CMC development consists of early- and late-stage process development to ensure sufficient mAb manufacturing yield and consistent product quality for patient safety and efficacy. Here, we report a case study of late-stage cell culture process development at pandemic speed for mAb1 and mAb2 production as a combination therapy for a highly unmet patient treatment. We completed late-stage cell culture process characterization (PC) within approximately 4 months from the cell culture process definition to the initiation of the manufacturing process performance qualification (PPQ) campaign for mAb1 and mAb2, in comparison to a standard one-year PC timeline. Different strategies were presented in detail at different PC steps, i.e., pre-PC risk assessment, scale-down model development and qualification, formal PC experiments, and in-process control strategy development for a successful PPQ campaign that did not sacrifice quality. The strategies we present may be applied to accelerate late-stage process development for other biologics to reduce timelines.

Stability Modelling of mRNA Vaccine Quality Based on Temperature Monitoring throughout the Distribution Chain.

The vaccine distribution chains in several low- and middle-income countries are not adequate to facilitate the rapid delivery of high volumes of thermosensitive COVID-19 mRNA vaccines at the required low and ultra-low temperatures. COVID-19 mRNA vaccines are currently distributed along with temperature monitoring devices to track and identify deviations from predefined conditions throughout the distribution chain. These temperature readings can feed into computational models to quantify mRNA vaccine critical quality attributes (CQAs) and the remaining vaccine shelf life more accurately. Here, a kinetic modelling approach is proposed to quantify the stability-related CQAs and the remaining shelf life of mRNA vaccines. The CQA and shelf-life values can be computed based on the conditions under which the vaccines have been distributed from the manufacturing facilities via the distribution network to the vaccination centres. This approach helps to quantify the degree to which temperature excursions impact vaccine quality and can also reduce vaccine wastage. In addition, vaccine stock management can be improved due to the information obtained on the remaining shelf life of mRNA vaccines. This model-based quantification of mRNA vaccine quality and remaining shelf life can improve the deployment of COVID-19 mRNA vaccines to low- and middle-income countries.

Rational Development of a Carrier-Free Dry Powder Inhalation Formulation for Respiratory Viral Infections via Quality by Design: A Drug-Drug Cocrystal of Favipiravir and Theophylline.

Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility. An ultra-high oral dose is essential, causing low patient compliance. This study reports a Quality-by-Design (QbD)-guided development of a carrier-free inhalable dry powder formulation containing a 1:1 favipiravir-theophylline (FAV-THP) cocrystal via spray drying, which may provide an alternative treatment strategy for individuals with concomitant influenza infections and chronic obstructive pulmonary disease/asthma. The cocrystal formation was confirmed by single crystal X-ray diffraction, powder X-ray diffraction, and the construction of a temperature-composition phase diagram. A three-factor, two-level, full factorial design was employed to produce the optimized formulation and study the impact of critical processing parameters on the resulting median mass aerodynamic diameter (MMAD), fine particle fraction (FPF), and crystallinity of the spray-dried FAV-THP cocrystal. In general, a lower solute concentration and feed pump rate resulted in a smaller MMAD with a higher FPF. The optimized formulation (F1) demonstrated an MMAD of 2.93 µm and an FPF of 79.3%, suitable for deep lung delivery with no in vitro cytotoxicity observed in A549 cells.

Accelerating evidence generation through quality by design

The concept of applying Quality by Design to clinical trials is increasingly accepted and is becoming common clinical trials vocabulary. In addition to ongoing incorporation in global regulatory frameworks (ICH E8), the approach is being successfully applied in a range of both academic and industry studies to streamline designs, and to proactively identify and address factors that are likely to significantly impede the conduct of the study, place trial participants at unnecessary risk, or impede usability of the resulting data (in other words, to become ''errors that matter''). This panel discussion will provide attendees with the information and resources they need to begin or enhance their implementation of Quality by Design, and will: (1) share case studies highlighting diverse models of implementation and lessons learned;(2) discuss implementation maturity and approaches for planning and tracking progress over time;and (3) engage the audience in discussion around understanding and applying key concepts, including identifying critical-to-quality factors, proactively addressing important risks to study quality, and engaging the broad range of stakeholders in study design. Discussion will include design-related lessons learned and best practices identified during the COVID-19 pandemic. Attendees will walk away with a better understanding of the importance and benefits of a Quality by Design approach, and be armed with new tools and insights to support rigorous, high-quality clinical trials that meaningfully advance public health. Speakers will be drawn from Clinical Trials Transformation Initiative's multi-stakeholder project team, and we anticipate including one or more principal investigators with direct experience implementing Quality by Design at academic health centers (likely drawn from Duke, University of California Irvine, Georgetown, Kansas University Medical Center, and/ or Oxford, depending on global travel conditions), as well as regulatory and/or ICH E8 working group, patient, and industry perspectives.

A QbD Approach for Evaluating the Effect of Selective Laser Sintering Parameters on Printability and Properties of Solid Oral Forms.

The aim of this work was to investigate the effect of process parameters on the printability of a formulation containing copovidone and paracetamol, and on the properties of solid oral forms 3D-printed through selective laser sintering. Firstly, the influence of the heating temperature was evaluated individually, and it was revealed that this parameter was critical for printability, as a sufficiently high temperature (100 °C) is necessary to avoid curling. Secondly, the effects of laser power, scan speed, and layer thickness were determined using a Box-Behnken design. The measured responses, printing yield, height, weight, hardness, disintegration time, and percentage of drug release at 10 min showed the following ranges of values: 55.6-100%, 2.92-3.96 mm, 98.2-187.2 mg, 9.2-83.4 N, 9.7-997.7 s, and 25.8-99.9%, respectively. Analysis of variance (ANOVA) proved that the generated quadratic models and the effect of the three-process parameters were significant (p < 0.05). Yield improved at high laser power, low scan speed, and increased layer thickness. Height was proportional to laser power, and inversely proportional to scan speed and layer thickness. Variations in the other responses were related to the porosity of the SOFs, which were dependent on the value of energy density. Low laser power, fast scan speed, and high layer thickness values favored a lower energy density, resulting in low weight and hardness, rapid disintegration, and a high percentage of drug release at 10 min. Finally, an optimization was performed, and an additional experiment validated the model. In conclusion, by applying a Quality by Design approach, this study demonstrates that process parameters are critical for printability, but also offer a way to personalize the properties of the SOFs.

Feasibility and acceptability of a structured quality by design approach to enhancing the rigor of clinical studies at an academic health center.

INTRODUCTION: Clinical trials are a critical step in the meaningful translation of biomedical discoveries into effective diagnostic and therapeutic interventions. Quality by design (QbD) is a framework for embedding quality into the design, conduct, and monitoring of clinical trials. Here we report the feasibility and acceptability of a process for implementing QbD in clinical research at an academic health center via multidisciplinary design studios aimed at identifying and prioritizing critical to quality (CTQ) factors. METHODS: The Clinical Trial Transformation Initiative's Principles Document served as a guide to identify and categorize key CTQ factors, defined as elements of a clinical trial that are critical to patient safety and data integrity. Individual trials were reviewed in CTQ design studios (CTQ-DS) and the feasibility and acceptability of this intervention was examined through post-meeting interviews and surveys. RESULTS: Eight clinical research protocols underwent the QbD evaluation process. The protocols ranged from multicenter randomized clinical trials to nonrandomized investigator-initiated studies. A developmental evaluation informed the iterative refinement of the CTQ-DS process, and post-meeting surveys revealed that CTQ-DS were highly valued by principal investigators (PIs) and resulted in multiple protocol changes. CONCLUSIONS: The present study demonstrated that QbD principles can be implemented to inform the design and conduct of clinical research at an academic health center using multidisciplinary design studios aimed at identifying and prioritizing CTQ elements. This approach was well received by the participants including study PIs. Future research will need to evaluate the effectiveness of this approach in improving the quality of clinical research.

Making trials part of good clinical care: lessons from the RECOVERY trial.

When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.

Stability Indicating LC Method Development for Hydroxychloroquine Sulfate Impurities as Available for Treatment of COVID-19 and Evaluation of Risk Assessment Prior to Method Validation by Quality by Design Approach.

A quality by design-based stability indicating HPLC method has been developed for hydroxychloroquine sulfate impurities. The optimized HPLC method can detect and quantify the hydroxychloroquine sulfate and related organic impurities in pharmaceutical solid oral dosage forms. Nowadays, for the quantification of impurities in drug products demands more comprehensive way of analytical method development. The quality by design approach allows the assessment of different analytical parameters and their effects with minimum number of experiments. A highly sensitive and stability indicating RP-HPLC method was developed and evaluated the risk assessment prior to method validation. The chromatographic separation was achieved with X-terra phenyl column (250 × 4.6 mm, 5 µm) using phosphate buffer (0.3 M and pH 2.5). The gradient method flow rate was 1.5 mL min-1 and UV detection was made at 220 nm. The calibration curve of hydroxychloroquine sulfate and related impurities were linear from LOQ to 150% and correlation coefficient was found more than 0.999. The precision and intermediate precision % RSD values were found less than 2.0. In all forced degradation conditions, the purity angle of HCQ was found less than purity threshold. The optimized method found to be specific, accurate, rugged, and robust for determination of hydroxychloroquine sulfate impurities in the solid oral dosage forms. Finally, the method was applied successfully in quality control lab for stability analysis.

Four-step approach to efficiently develop capillary gel electrophoresis methods for viral vaccine protein analysis.

Vaccines against infectious diseases are urgently needed. Therefore, modern analytical method development should be as efficient as possible to speed up vaccine development. The objectives of the study were to identify critical method parameters (CMPs) and to establish a set of steps to efficiently develop and validate a CE-SDS method for vaccine protein analysis based on a commercially available gel buffer. The CMPs were obtained from reviewing the literature and testing the effects of gel buffer dilution. A four-step approach, including two multivariate DoE (design of experiments) steps, was proposed, based on CMPs and was verified by CE-SDS method development for: (i) the determination of influenza group 1 mini-hemagglutinin glycoprotein; and (ii) the determination of polio virus particle proteins from an inactivated polio vaccine (IPV). The CMPs for sample preparation were incubation temperature(s) and time(s), pH, and reagent(s) concentration(s), and the detection wavelength. The effects of gel buffer dilution revealed the CMPs for CE-SDS separation to be the effective length, the gel buffer concentration, and the capillary temperature. The four-step approach based on the CMPs was efficient for the development of the two CE methods. A four-step approach to efficiently develop capillary gel electrophoresis methods for viral vaccine protein analysis was successfully established.

Rapid development and deployment of high-volume vaccines for pandemic response.

Overcoming pandemics, such as the current Covid-19 outbreak, requires the manufacture of several billion doses of vaccines within months. This is an extremely challenging task given the constraints in small-scale manufacturing for clinical trials, clinical testing timelines involving multiple phases and large-scale drug substance and drug product manufacturing. To tackle these challenges, regulatory processes are fast-tracked, and rapid-response manufacturing platform technologies are used. Here, we evaluate the current progress, challenges ahead and potential solutions for providing vaccines for pandemic response at an unprecedented scale and rate. Emerging rapid-response vaccine platform technologies, especially RNA platforms, offer a high productivity estimated at over 1 billion doses per year with a small manufacturing footprint and low capital cost facilities. The self-amplifying RNA (saRNA) drug product cost is estimated at below 1 USD/dose. These manufacturing processes and facilities can be decentralized to facilitate production, distribution, but also raw material supply. The RNA platform technology can be complemented by an a priori Quality by Design analysis aided by computational modeling in order to assure product quality and further speed up the regulatory approval processes when these platforms are used for epidemic or pandemic response in the future.