ROCKY ROAD AHEAD FOR NEW FDA CHIEF CALIFF

Final Senate approval by a historically narrow 50-46 vote came only after the White House and Califf's supporters lobbied hard to gain sufficient support, a success that is very different from Califf's 89-4 approval back in 2016. Pressure to help control the high cost of prescription drugs will continue to drive FDA support for developing complex generic drugs and biosimilars. There is pressure to clarify rules governing e-cigarettes;a need to address serious health problems arising from contaminated food and seafood, including significant volumes of imported products;and the safety of cosmetic products, dietary supplements, sunscreens, and other non-prescription products raise additional complex issues.

PANDEMIC ALTERS POLICIES FOR DRUG DEVELOPMENT

The desperate need for new vaccines and therapies to tame the deadly COVID-19 virus required new policies and procedures for how biopharma companies select, test, and manufacture medical products-and revised regulatory practices for evaluating clinical data, manufacturing operations, and procedures for submitting and analyzing information. Vaccine experts at the Center for Biologics Evaluation and Research (CBER) worked overtime to clarify the size and diversity of efficacy trials and key analytical assessments needed to gain EUA status and later full approval, establishing standards and procedures that will shape research for health emergencies to come. Officials at FDA's Office of Regulatory Affairs (ORA) indicate that the agency will continue to utilize many of these strategies for streamlining oversight of manufacturing operations, even as on-site visits increase overseas and at home, leading to a more "hybrid" inspection process going forward.

FDA CAUGHT IN POLITICAL CROSSFIRE

FDA's oversight of medical devices and diagnostics has put it in the hot seat for shortages of critical products for protecting medical personnel and for providing fast and accurate public testing for COVID infection. The result is that the White House has delayed in selecting an FDA commissioner, even though federal rules require Woodcock to vacate her acting position by mid-November unless the administration nominates a new commissioner, permitting her to continue on during the Senate confirmation process. The approval decision by CDER officials was blasted by members of Congress, the medical community and even some patient groups, but justified by the reviewers as likely to provide some benefit to some patients who lacked any alternative treatment for this devastating disease.

DIVERSITY IN CLINICAL TRIALS GAINS GROUND AMIDST COVID

More recent policies aim to offset years of underenrollment of minority groups by expanding enrollment criteria, including more research sites in minority communities, and engaging investigators with diverse backgrounds. FDA has also sought to promote research diversity through its Drug Trials Snapshots program, established in 2015 to increase the visibility of clinical trial enrollment by age, sex, ethnicity and race. According to a recent report on the program's impact, though, there still may be a ways to go for clinical trials to reflect the diversity of the US population.

BIDEN SEEKS ADDED FUNDING FOR RESEARCH, DISEASE TRACKING

To better prepare for the next pandemic, the White House seeks a significant increase in discretionary funding for the Centers for Disease Control and Prevention (CDC), proposing a $1.6 billion increase to an $8.7 billion budget able to modernize data collection and boost support for local health departments. ARPA-H initially would focus on cancer, diabetes and Alzheimer's disease and is modeled after the military's Defense Advanced Research Projects Agency (DARPA), with project funding decisions made by program managers, as opposed to the peer-review process of NIH research institutes. In addition to funding genomic sequencing capacity on the state and federal level, the new program would build a National Bioinformatics Infrastructure throughout the public health system.

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.

PANDEMIC SPURRED NEW R&D APPROACHES FROM PHARMA, FDA IN 2022

The article offers information on the ongoing surge in Research and Development for cell and gene therapies prompted a reorganization and expansion of Food and Drug Administration (FDA) offices overseeing these products and efforts to clarify and update regulatory policies in the area. It discusses that FDA recognized the challenges in overseeing these developments as it moved to revive field inspection operations for manufacturing facilities and bioresearch operations.

FDA CAUGHT IN POLITICAL CROSSFIRE

The article informs that the U.S. Food and Drug Administration (FDA)'s oversight of medical devices and diagnostics has seat for shortages of critical products for protecting medical personnel and for providing fast and accurate public testing for COVID infection. Topics include continuing wave of false claims popular treatments to combat the pandemic sidelined by Democrats and public health;and long-time head of drug development and approval at the Center for Drug Evaluation and Research.

FDA PROMOTES MASTER PROTOCOLS TO MODERNIZE CLINICAL TRIALS

The article report that the FDA has responded to the pressures by generating multiple guidance documents and policy initiatives for updating and advancing the clinical research process. Topics discussed include the research programs to facilitate the development of safety and effectiveness information for multiple test therapies in a compressed time period;and the guidance aims to overcome fairly limited use of master protocols in the U.S. by clarifying for sponsors FDA's recommendations.