Preparing Pandemic Vaccine Capacity

Among the challenges of a pandemic is the need to scale up to billions of doses, at a larger scale than typically needed for vaccines, from raw materials all the way through to the materials for the containers for fill/finish. Having adequate raw materials, building and staffing the facilities, and tech transfer are all keys to success. [...]we can plug into existing infrastructure, including services (gas, water, waste, etc.) as well as analytics and quality labs." Emergent BioSolutions says that its flexible CDMO capacity deployment model can respond quickly to demand fluctuations. The company's facilities in France, Switzerland, and the US are working on the project;at CordenPharma Colorado, unique high-pressure chromatography systems usually used for manufacturing peptides have been reallocated for purifying lipids.

Impact of Pandemic on Permanent Procedures

Conducting virtual audits, conducting effective virtual training, and enhancing communications with suppliers to ensure an uninterrupted supply chain are among the changes implemented to maintain operations, stay compliant, and continue manufacturing medically necessary products. The necessity for virtual audits was to allow companies and regulators to continue to evaluate the compliance stature of manufacturers while respecting stay-at-home and social distancing requirements that prevented in-person site audits. Some of these venues are free, and some require a registration fee. supply chain quality Enhanced communication with suppliers to ensure an uninterrupted supply chain has also become a priority during the pandemic.

Following Guidelines During a Crisis

The guidance states, "These preventative measures can include steps to prepare personnel such as: * "Educating employees on topics such as, in the case of a pandemic, personal hygiene (hand washing and coughing and sneezing etiquette), social distancing, and appropriate use of sick leave * "Encouraging employees to get immunized as appropriate by providing information on local vaccination services or by offering on-site vaccination services, if reasonable * "Providing information for and encouraging employees to develop family emergency preparedness plans * "Reviewing CGMP [current good manufacturing practice] regulations regarding appropriate sanitation practices and restriction of ill or sick employees from production areas (see 21 CFR [Code of Federal Regulations] 211.28)" (2). Examples include: * "Production equipment routine maintenance * "Utility system performance checks and maintenance (e.g., air temperature, lighting, compressed air) * "Environmental monitoring of facilities such as cell culture, harvesting, and purification rooms during production * "Stability testing for certain drug products and components * "Periodic examinations of data and of reserve samples" (2). EMA, Guidance on the Format of the Risk Management Plan (RMP) in the EU-in Integrated Format, EMA/164014/2018 Rev.2.0.1 accompanying GVP Module V Rev.2 Human Medicines Evaluation (EMA, 31 October 2018).

How to Keep Home Healthcare on Target

Home visits have the power to ease the clinical trial process for patients, but complex study design, tight timelines, busy clinical operations teams, and overburdened sites can sometimes make home health feel like yet another moving piece to manage. Individual variables that play a large role in establishing timelines can include factors like: * Amount of protocol-specific training required. * Level of engagement during a visit. * On-site processing requirements. * Drug or sample stability. * Recruitment goals. [...]all training should be to the full satisfaction of the principal investigator overseeing the study. Since sites are still responsible for the conduct of home visits from a regulatory perspective, there is often a concern about how they can remain in control of the progress without overwhelming the already busy study team and staff.

Covid-19: Rest and PPE reassurance are needed before NHS services can restart, MPs hear

At a Health and Social Care Select Committee evidence session on 14 May the King's Fund, the Nuffield Trust, and the Health Foundation warned that it would take many more months before core health and care services were able to fully restart. Limited capacity Jennifer Dixon, chief executive officer at the Health Foundation, told the committee that capacity within hospitals would be severely limited because of the need for social distancing, separating out covid and non-covid patients, and more time for deep cleaning of equipment and facilities. Chris Hopson, chief executive officer at NHS Providers, told the committee that NHS staff had worked incredibly hard in the past few months, with leave cancelled, and were very tired as a result.

Covid-19: MPs call on Public Health England to publish evidence for decision to drop community testing

A cross party group of MPs has said that Public Health England's failure to publish the evidence behind its decision to discontinue community testing at the start of the covid-19 outbreak is "unacceptable.” In a 19 page letter to the prime minister, the Science and Technology Committee called for publication of the evidence base and rationale informing Public Health England's decision to concentrate testing for covid-19 in a limited number of its own laboratories and to expand testing capacity gradually, rather than surging capacity through a large number of available laboratories in research institutes, universities, and the public and private sectors.1 This had led to the government announcing on 12 March that testing would stop in the community and would occur principally within hospitals—a decision that was "one of the most consequential made during [the] crisis,” MPs said in the letter. The committee chair, Greg Clark, said, "Greater transparency around scientific advice;putting capacity in place in advance of need, such as in testing and vaccines;collecting more data earlier;and learning from other countries' approaches are some of the early lessons of this pandemic that are relevant to further decisions that will need to be taken during the weeks and months ahead.”

WASHINGTON REPORT

FNIH will manage an ACTIV steering committee to develop an inventory of potential candidates, launch master protocols with a single control arm, and set criteria for ranking potential candidates for first-wave and subsequent evaluation. [...]a third group will tap NIH's extensive clinical trial network infrastructure to build capacity for expediting trials and to study different populations and disease stages. ?o advance vaccine development, another ACTIV group will form a collaborative framework to map epitopes and develop assays, establish protocols for sampling and immunological analyses, collect clinical data on immunological responses and endpoints, and engage with regulators on surrogate endpoints for clinical evaluation. Jill Wechsler MULTIPLE WEBSITES IDENTIFY AND TRACK RESEARCH ON COVID Widespread research activity is available from these and other organizations: * The University of Oxford Center for Evidence-Based Medicines lists more than 1000 clinical trials at http:// covid19.trialstracker.net/index.html * Bill & Melinda Gates Foundation with Cytel identifies more than 600 trials in the US and other regions at https://covid19-trialscom * TranspariMed offers a guide to multiple trials at https://www.transparimed.org/ * Bi°Century tracks vaccines and therapeutics in its COVID-19 Resource Center, https://www.biocentury.com/ clinical-vaccines-and-therapies * World Health Organization: https://www. who.int/emergencies/diseases/novelcoronavirus-2019/global-researchon-novel-coronavirus-2019-ncov/ * Regulatory Affairs Professionals Society: https://www.raps.org/newsand-articles/news-articles/2020/3/ covid-19-therapeutics-tracker

INDUSTRY BACKS CLEAR FDA VACCINE STANDARDS

In spelling out the data expected for such authorization, agency officials emphasized the importance of fully vetting the safety and efficacy of any new coronovirus vaccine through a highly transparent process to boost public confidence in the ability of vaccines to save lives. Countering vaccine hesitancy Through the debate, officials in the Center for Biologics Evaluation and Research (CBER) emphasized that the EUA safety data requirement was already well known to vaccine manufacturers and that one aim was to assure manufacturers that FDA would hold all vaccine development programs to the same standards. Center for Biologics Evaluation and Research (CBER) Director Peter Marks further emphasized that the guidance sought to reassure the public that granting an EUA would not be a rushed decision on vaccine safety and efficacy to meet political goals, and that a vaccine EUA would require more data than for the more usual emergency authorizations for therapeutics and other medical products.

FDA'S 'GOLD STANDARD' CRITICAL FOR BIOPHARMA R&D

Last week, eight prominent biotech industry executives publicly emphasized the importance of rigorous clinical research and complete study data to support any authorization or approval of a new covid vaccine or treatment. Hahn raises concerns These statements aim to offset fears that fda might soften its approval standards due to pressure from the White House to make available a covid vaccine in October. Continuing predictions from the White House about a vaccine being available in two months, and instructions from the Centers for Disease Control and Prevention (CDC) that state public health departments should be prepared to distribute a vaccine by the end of October, heightened concerns that political pressure will lead to some kind of authorization of a new vaccine before the Nov. 3 election.

Early Vaccine Authorization Raises Ethical and Logistical Challenges for Trial Sponsors

The much-anticipated meeting of FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) last month addressed a number of critical issues related to testing and approval of vaccines to prevent COVID-19 infection, including policies and data requirements for determining that a pandemic vaccine can be considered safe and effective, particularly when based on more limited, early clinical trial data. While studies sponsored by AstraZeneca and Johnson & Johnson's Janssen unit resumed soon after the meeting, the study pauses were described by researchers as a sign that clinical trial safety systems were working as intended, as the analysts determined the adverse events were unrelated to the test vaccine candidates. The aim is to gain further information on vaccine efficacy and side effects, including rare adverse events and fuller comparisons among patient groups with differences in age, sex, comorbidities, and ethnic characteristics.

DEBATE ACCELERATES OVER WHO GETS COVID VACCINE FIRST

At the agencies' request, the National Academy of Sciences, Engineering and Medicine iNASEMi has formed a blue-ribbon committee of leading bioethicists, economists, geneticists, and public health authorities to quickly develop a framework for priority vaccine access to assist policymakers in the U.S. and other nations achieve equitable distribution of anticipated vaccines (see: https://bit.ly/33jTCds). Individuals at higher risk will include those in higher age groups, with underlying health conditions, engaged in high-risk occupations, affected by racial and ethnic disparities, and in hardhit geographic locations. State and public health officials are wary of federal pandemic planning efforts so fair given the lack of coordination and effectiveness in distributing COVID-19 test kits and personal protective equipment to healthcare providers and facilities.

COVID ADVANCES CLINICAL TRIAL TRANSPARENCY

Growing public concerns about politics playing a role in vetting potential vaccines and therapies to combat the COVID-19 pandemic has prompted sponsors of leading clinical trials to make public their study protocols and statistical analysis plans. [...]AstraZeneca's timeframe for enrolling and assessing study participants was delayed by the need to address the report of a serious adverse event in its Phase III study. The disclosure of these usually confidential details on research endpoints, assessment timeframes, and study analysis plans aim to promote information sharing among vaccine developers, and also build public confidence.

CLINICAL TRIAL REFORM

[...]CURES' BILL PROMOTES PANDEMIC PREPAREDNESS Congressional leaders are developing the next version of the 21st Century Cures Act, including provisions to advance research related to the COVID-19 crisis as part of initiatives for bringing innovative therapies to market faster (see https://bit.ly/2SKfA4S). Cures 2.0 continues and updates some of the main themes of the first Cures Act: support development of treatments for rare diseases, patient-focused drug development, diversity in clinical trials, expanded use of digital health systems, increased health literacy, and utilization of real-world data. A public education campaign, moreover, would aim to counter concerns about the safety of vaccines to promote widespread vaccination. Because these treatments are costly and unprofitable for biopharma companies to test and market, the legislation proposes additional financial support for both pre-market studies and post-market production and subsidized higher reimbursement rates for antibiotics that address critical needs.

Lack of efficacy of hydroxychloroquine in covid-19

Studies in mild-to-moderate cases as well as severe disease leave us still searching for a magic pill

Addressing the Needs of Clinical Trial Sites in a Post-COVID-19 World

[...]many sponsors have implemented alternative ways to conduct trials or components of them, incorporating remote and virtual activities, which aim to bring studies directly to patients via a range of technologies. Every clinical investigation begins with the development of a protocol that describes h.ow a clinical trial will be conducted-encompassing the objective(s), design, methodology, statistical considerations, and organization of the study-and ensures the safety of the trial subjects and integrity of the data collected. [...]of the pandemic, we will see more hybrid trials that combine site and remote patient visits. In forcing the research community to be more open to using different tools to ensure vital research continues, the pandemic is driving the beginning of a new era of patient and site engagement-one in which a more proactive and efficient approach ensures the lines of communication remain open and data is collected appropriately and with greater speed.