A Proposal to Increase Value and Equity in the Development and Distribution of New Pharmaceuticals.

The process of developing and marketing new pharmaceuticals in the United States is driven by a need to maximize returns to shareholders. This results all too often in the production of new medications that are expensive and of marginal value to patients and society. In line with our heightened awareness of the importance of social justice and public health-and in light of our government's alliance with private companies in bringing us COVID-19 vaccines-we need to reconsider how new pharmaceuticals are developed and distributed. Accordingly, we propose the creation of a new agency of the Food and Drug Administration (FDA) that would direct the whole process. This agency would fund the research and development of high-value medications, closely monitor the clinical studies of these new drugs, and manage their distribution at prices that are value-based, fair, and equitable.

Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines-Selecting Compounds for Clinical Evaluation in Coronavirus Disease 2019 Clinical Trials.

Given the urgent need for coronavirus disease 2019 therapeutics, early in the pandemic the Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership rapidly designed a unique therapeutic agent intake and assessment process for candidate treatments of coronavirus disease 2019. These treatments included antivirals, immune modulators, severe acute respiratory syndrome coronavirus 2 neutralizing antibodies, and organ-supportive treatments at both the preclinical and clinical stages of development. The ACTIV Therapeutics-Clinical Working Group Agent Prioritization subgroup established a uniform data collection process required to perform an assessment of any agent type using review criteria that were identified and differentially weighted for each agent class. The ACTIV Therapeutics-Clinical Working Group evaluated over 750 therapeutic agents with potential application for coronavirus disease 2019 and prioritized promising candidates for testing within the master protocols conducted by ACTIV. In addition, promising agents among preclinical candidates were selected by ACTIV to be matched with laboratories that could assist in executing rigorous preclinical studies. Between April 14, 2020, and May 31, 2021, the Agent Prioritization subgroup advanced 20 agents into the Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines master protocols and matched 25 agents with laboratories to assist with preclinical testing.

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV): Designing Master Protocols for Evaluation of Candidate COVID-19 Therapeutics.

Working in an unprecedented time frame, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership developed and launched 9 master protocols between 14 April 2020 and 31 May 2021 to allow for the coordinated and efficient evaluation of multiple investigational therapeutic agents for COVID-19. The ACTIV master protocols were designed with a portfolio approach to serve the following patient populations with COVID-19: mild to moderately ill outpatients, moderately ill inpatients, and critically ill inpatients. To facilitate the execution of these studies and minimize start-up time, ACTIV selected several existing networks to launch the master protocols. The master protocols were also designed to test several agent classes prioritized by ACTIV that covered the spectrum of the disease pathophysiology. Each protocol, either adaptive or pragmatic, was designed to efficiently select those treatments that provide benefit to patients while rapidly eliminating those that were either ineffective or unsafe. The ACTIV Therapeutics-Clinical Working Group members describe the process by which these master protocols were designed, developed, and launched. Lessons learned that may be useful in meeting the challenges of a future pandemic are also described.

Preparing for the Next Normal: Transformation in the Role of Medical Affairs Following the COVID-19 Pandemic.

The medical affairs function represents one of the scientific interfaces in a pharmaceutical organization. Over the last two decades, medical affairs has evolved from being a support function to a strategic pillar within organizational business units. The COVID-19 pandemic has given rise to unforeseen circumstances resulting in a dramatic change in external stakeholder engagements, catapulting the medical affairs function into leading the way on scientific engagements and patient-centric endeavors. The changes in stakeholder interactions and behavior as a result of the pandemic last year are likely to persist in the foreseeable future for which medical affairs professionals need to enhance existing skill sets and acquire expertise in newer domains. In this paper, the transformation of the medical affairs team to a key strategic partner and the skills required to strengthen this transition, in the next normal of a post-COVID world, is explored.

Operation Warp Speed: implications for global vaccine security.

Several global efforts are underway to develop COVID-19 vaccines, and interim analyses from phase 3 clinical testing have been announced by nine organisations: Pfizer, the Gamaleya Research Institute of Epidemiology and Microbiology, Moderna, AstraZeneca, Sinopharm Group, Sinovac Biotech, Johnson & Johnson, Novavax, and CanSino Biologics. The US programme known as Operation Warp Speed provided US$18 billion in funding for development of vaccines that were intended for US populations. Depending on safety and efficacy, vaccines can become available through mechanisms for emergency use, expanded access with informed consent, or full licensure. An important question is: how will these Operation Warp Speed vaccines be used for COVID-19 prevention in global health settings? We address some key questions that arise in the transition from US to global vaccine prevention efforts and from ethical and logistical issues to those that are relevant to global vaccine security, justice, equity, and diplomacy.

[COVID-19: Warp Speed vaccines]. / COVID-19, des vaccins à la vitesse de l'éclair.

A vaccine is required to effectively control the COVID-19 pandemic in the mid and long term. The development of vaccines against SARS-CoV-2 was initiated as soon as the genetic sequence of the virus was published, and has evolved at an unprecedented speed, with a first clinical trial launched in March 2020. One year later, more than a dozen of vaccines based on different concepts, with some having been evaluated only in clinical trials so far, are authorized under emergency procedures. Here, we review these vaccines, compare their properties and discuss the challenges they face, including the emergence of viral variants of concern.

TITLE: COVID-19, des vaccins à la vitesse de l'éclair. ABSTRACT: Un vaccin est nécessaire pour endiguer efficacement, à moyen et long terme, une pandémie comme celle de la COVID-19 (coronavirus disease 2019). Le développement de vaccins contre le virus responsable de la maladie, le SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2), a été débuté dès la publication de la séquence du génome viral. Ce développement a progressé à une vitesse sans précédent, avec un premier essai clinique réalisé peu de temps après, en mars 2020. Un an plus tard, une dizaine de vaccins reposant sur des concepts différents, dont certains n'avaient été testés que dans des essais cliniques, sont autorisés dans le cadre de procédures d'urgence. Dans cet article, nous passons en revue ces différents vaccins, nous comparons leurs propriétés et nous discutons les défis auxquels ils sont confrontés, en particulier l'émergence de nouveaux variants viraux.

Revamping the ever-changing landscape of drug development processes in the midst of COVID-19 pandemic.

Oncology is the frontline of drug development. The current pharmaceutical pipeline is disproportional focused on oncology, where about 1/3 of all phases of development is in this therapeutic area. The emphasis brings about substantial breakthroughs and has made positive impact on the quality of life. However, oncology remains a threat to human existence. To facilitate this process, a comprehensive list of novel/first molecularly targeted oncology drug approvals by the FDA from 2017 to 2020 is assessed. Here, we focus on molecularly targeted oncology drugs and not cytotoxic ones, although the latter remain important. To achieve this purpose, besides their sponsors, years of approval, drug classes, and cancer indications, clinical significance is included. The results show that approved molecularly targeted drugs span across diverse classes, including small molecule receptor inhibitors, and biologics such as monoclonal antibodies, antibody-drug conjugates, check-point inhibitors (i.e., PD1, PDL1, CTLA4) and CAR-T cell therapies. Although complete cure of cancer remains limited, we have made substantial inroads and more is yet to come. Moreover, many of these new knowledge can be extrapolated to other therapeutic areas, especially to those of currently unmet medical needs such as in neurology and other chronic diseases.

The Costs of Contradictory Messages About Live Vaccines in Pregnancy.

The increased risk of harm from COVID-19 infection in pregnancy highlights the importance of including pregnant people in COVID-19 vaccine development and deployment. Promising vaccines being developed include replication-competent platforms, which are typically contraindicated during pregnancy because of theoretical risk. However, replicating vaccines are administered in and around pregnancy, either inadvertently because of unknown pregnancy status or when recommended.The historical cases of Ebola virus, yellow fever, and rubella demonstrate that contradictory messages around the safety of live vaccines in pregnancy have critical public health costs. First, restricting study or use of replicating vaccines in pregnancy may delay or deny access to the only available protection against deadly diseases. Additionally, not vaccinating pregnant people may slow epidemic control. Finally, uncertainty and worry around the safety of live vaccines may lead to terminations of otherwise desired pregnancies after inadvertent vaccination in pregnancy.If one of the vaccines deployed to combat the current global COVID-19 pandemic is replication competent, historical cases offer important lessons for ethical and effective protection for pregnant populations.

Vaccine development: Covid-19 and beyond.

With Covid-19 vaccines being developed at a rapid pace, Josh Loeb and Julienne Wooster ask why the most sought-after vaccines for animal diseases cannot be developed as quickly.

Perspectives on Virtual (Remote) Clinical Trials as the "New Normal" to Accelerate Drug Development.

Although the digital revolution has transformed many areas of human endeavor, pharmaceutical drug development has been relatively slow to embrace the emerging technologies to enhance efficiency and optimize value in clinical trials. The topic has garnered even greater attention in the face of the coronavirus disease 2019 (COVID-19) outbreak, which has caused unprecedented disruption in the conduct of clinical trials and presented considerable challenges and opportunities for clinical trialists and data analysts. In this paper, we highlight the potential opportunity with virtual or digital clinical trials as viable options to enhance efficiency in drug development and, more importantly, in offering diverse patients easier and attractive means to participate in clinical trials. Special reference is made to the implication of artificial intelligence and machine-learning tools in trial execution and data acquisition, processing, and analysis in a virtual trial setting. Issues of patient safety, measurement validity, and data integrity are reviewed, and considerations are put forth with reference to the mitigation of underlying regulatory and operational barriers.

New Approaches to Regulatory Innovation Emerging During the Crucible of COVID-19 : In Responding to a Global Health Crisis, Industry is Discovering New, Efficient Ways of Meeting Objectives.

The urgency and impact of the ongoing COVID-19 pandemic are changing global drug development and regulatory processes. The need for speed to understand the virus and develop new vaccines, medicines, and therapies for patients has provided unprecedented learning opportunities and revealed how the pharmaceutical industry can improve upon traditional processes. To stay competitive while remaining compliant with agency regulations and guidance, companies need to implement new process/tools that allow for more flexible work models, consider expanding the use of decentralized/hybrid trials, and capitalize on the use of real-world evidence (RWE) and cloud-based data systems. In addition, regulatory agencies should retain the agility exhibited during current reviews of potential new therapies, applying this momentum to other areas of unmet medical need. Further, agencies should consider a globally acceptable application platform. This article, by the Pharmaceuticals' Head of Regulatory Affairs at Bayer AG, examines how impacts of the COVID-19 crisis will continue beyond the pandemic period to the benefit of patients, drug developers, regulators, clinicians, and caregivers.

COVID-19 Vaccine Development to Vaccination.

In the race for a safe and effective vaccine against Coronavirus disease-19 manufacturer plays a critical role throughout the development, clinical trial, manufacturing, supply, and vaccination phases. For the efficacy of Coronavirus disease-19 vaccine, proper transport, storage, vaccine carrier, adjuvant, dosage form and route of vaccine administration plays a crucial role for immune response. In the context of no more people were willing to pay for a Coronavirus disease-19 vaccine the logistics of manufacturing, storing and distributing the vaccine, and mass vaccination are essential. It is urgent to improve health promotion and reduce the barriers to Coronavirus disease-19 vaccination. Keywords: COVID-19; vaccine development; vaccination.

Clinical trial preparations for the next pandemic.

This paper describes the need to prepare for the development of antiviral therapeutics for the next pandemic. Preparation would consist of a stockpiling of best practices for clinical trial design, analysis and operations during the current SARS-CoV-2 pandemic as well as continuous development of treatments and methodology between pandemics. This development would be facilitated by a global clinical trial pandemic reserve similar to the military reserves consisting of medical and quantitative methods professionals who would remain engaged between pandemics. Continuous identification of potential antiviral drugs and diagnostic methods would also be needed. Specific methodology addressed includes the importance of large simple trials, follow up time, efficacy endpoint, appropriate estimands, non-inferiority trials, more sophisticated patient accrual models and procedures for data sharing between clinical trials.