New science, drug regulation, and emergent public health issues: The work of FDA's division of applied regulatory science.

The U.S. Food and Drug Administration (FDA) Division of Applied Regulatory Science (DARS) moves new science into the drug review process and addresses emergent regulatory and public health questions for the Agency. By forming interdisciplinary teams, DARS conducts mission-critical research to provide answers to scientific questions and solutions to regulatory challenges. Staffed by experts across the translational research spectrum, DARS forms synergies by pulling together scientists and experts from diverse backgrounds to collaborate in tackling some of the most complex challenges facing FDA. This includes (but is not limited to) assessing the systemic absorption of sunscreens, evaluating whether certain drugs can convert to carcinogens in people, studying drug interactions with opioids, optimizing opioid antagonist dosing in community settings, removing barriers to biosimilar and generic drug development, and advancing therapeutic development for rare diseases. FDA tasks DARS with wide ranging issues that encompass regulatory science; DARS, in turn, helps the Agency solve these challenges. The impact of DARS research is felt by patients, the pharmaceutical industry, and fellow regulators. This article reviews applied research projects and initiatives led by DARS and conducts a deeper dive into select examples illustrating the impactful work of the Division.

Pharmacovigilance regulatory actions by national pharmacovigilance centers in Arab countries following COVID-19 pandemic.

BACKGROUND: Pharmacovigilance (PV) activities were affected by COVID-19. Therefore, several health authorities around the world have issued guidelines and practices to ensure that PV activities are maintained and continued during the pandemic. This study aimed to assess the impact of COVID-19 on the preparedness and performance of national PV systems in 14 Arab countries. RESEARCH DESIGN AND METHODS: This was a cross-sectional study that was conducted between July and October 2020. National PV centers in 18 Arab countries were invited to participate in this study. Descriptive analysis was used to summarize and present the results of this study. RESULTS: Responses were obtained from 14 (77.8%) countries. Adverse events reporting was the main PV activity that was covered by PV guidelines and practices. National guidelines and practices covered other PV activities in 8 (57.14%) of the participating countries. Performance and practices of national PV centers vary considerably among participating countries during the pandemic. CONCLUSION: The findings highlight the differences in preparedness and performance of different national PV centers in participating Arab countries. Improving digital infrastructure among participating countries could serve as a useful tool to minimize the impact of the pandemic on PV activities.

Implementing the Implementation Framework for Telemedicine to Address Non-Communicable Diseases in Thailand: What We Have Learned

For over two years, the coronavirus disease 2019 (COVID-19) has been spreading in Thailand and causing substantial disruption in noncommunicable disease (NCD) care. To resuscitate and develop telemedicine for NCD care, Thai NCD Collaboration Group has devised and carried out an implementation framework since 2020. In December 2021, disciplinary experts including NCD specialists, a pharmacist, health economists, a payer, and a policy decision-maker, reconvened to review the progress of implementation activities. Three key prioritized implementation activities were discussed. First, a simple protocol for hypertension management, which was to initiate the 'decentralize to primary care services' activity, was successfully developed and ready to roll out to multiple hospitals. Second, representatives from the Ministry of Public Health ensured that the 'telemedicine advocacy' activity was officially endorsed by the national health policy. They also acknowledged to support the implementation of the simple protocol at a national level. Third, for a 'drug regulation and quality' activity, a case study of limited access to cost-effective treatment was discussed, and an access strategy such as a co-payment model, was proposed as a potential solution to alleviate payer's budget constraint. Overall, the progress of implementation activities is positive, still, ongoing monitoring is important to drive telemedicine for NCD care to be fully operational and sustainable nationwide. Copyright © 2023 JOURNAL OF THE MEDICAL ASSOCIATION OF THAILAND.

A Review on Policies Adopted and Existing Drug Regulation Amended for Speedy Development of Vaccines in India

Objectives: To review transformation in the Govt. Policy and regulation accelerating product licensing for supporting timely Covid-19 vaccines in India. Method(s): Govt. policy for approval of vaccines and amendments of Drug regulations were studied during 1st January 2019 to 31st December 2021 were studied referring websites of Dept. of Health & Family Welfare, Govt. of India and website of CDSCO and analyzed. Result(s): Change in Government policies and amendment of Drug Rules in India have given opportunities for improving access to medicines and vaccines. The newly introduced New Drugs and Clinical Trial Rules have provisions to market drugs and vaccines without local clinical trials if, the new drug is approved and marketed in countries specified by the Central Licencing Authority (CLA) subject to some conditions. Thereafter CDSCO has published a guideline in this matter and the process of approving new vaccines becomes easier. This guidelines stated that no local clinical trials are required if a vaccine for Covid-19 already approved by USFDA, MHRA, PDMA Japan and listed by WHO for emergency use for Covid-19. These two steps helps quick approval for emergency use of vaccines already approved by CDSCO approved countries. Using these provisions Covid -19 vaccines developed by Moderna in US already got approval for import by an Indian company and hope that some more vaccines will be available in India in future using these provisions. Indian legislation allowed to conduct different phases of Clinical trials simultaneously resulting development of cost effective Covid-19 vaccines in shorter time. Conclusion(s): These proactive regulatory steps helped Indian manufacturers to develop Covid-19 vaccines in a record time and made it available in global market. These provisions also facilitated Covid -19 vaccines developed and marketed in developed market available in India. Copyright © 2022

Therapeutic delivery: industry update covering January 2022

This industry update covers the period from January 1 through January 31, 2022, and is based on information sourced from company press releases, scientific literature, patents and news websites. January 2022 saw Janssen and Midatech expand their collaboration on bioresorbable polymer microsphere technology for drug delivery. Takeda announced its plans to acquire UK-based Adaptate Biotherapeutics and Gandeeva raised further investment funds to support its drug discovery and development platform focused on the evaluation of protein-drug interactions. Biogen announced that it will sell its stake in a biosimilars joint venture and ABL Bio and Sanofi announced a collaboration around a novel treatment for Parkinson's disease. New regulatory announcements this month included US FDA approvals of a new insomnia treatment for Idorsia and a treatment for atopic dermatitis developed by Pfizer. Insulet gained FDA clearance for a closed-loop insulin pump and Ascendis Pharma followed up its United States approval last year for a once-weekly treatment for growth hormone deficiency with European approval. Pfizer and Ionis announced the discontinuation of the clinical development of a novel cardiovascular drug. In terms of collaborations, Novartis and Alnylam announced they will work together to explore targeted therapies to restore liver function;Scorpion Therapeutics partnered with AstraZeneca to develop novel cancer treatments and Nutriband Inc. and Kindeva Drug Delivery will work together to develop a transdermal fentanyl patch. Collaborations were also announced between Century Therapeutics and Bristol Myers Squibb and Lilly and Entos Pharmaceuticals in the areas of stem cell therapies for cancer treatment and neurology, respectively. A team from the Massachusetts Institute of Technology reported progress in developing oral mRNA treatments and West Pharmaceutical Services published a blog describing the development of a proof-of-principle system for a closed-loop feedback system targeting opioid overdose. A report on the BBC website highlighted the benefits of more sustainable inhalers.

Palliative Care for People Who Use Substances During Communicable Disease Epidemics and Pandemics: A Scoping Review

Background/aims: Communicable disease epidemics and pandemics magnify the health inequities experienced by marginalized populations. Given the pre-existing inequities to palliative care access for people with life-limiting illnesses who use substances, it is important to understand the impact of communicable disease epidemics and pandemics COVID-19 on this population. A scoping review was conducted to answer the research question, “what is known about communicable disease epidemics and pandemics, palliative care and people who use substances?” Methods: We conducted a scoping review of seven bibliographic databases from the inception of each database to April 2021. We also performed a grey literature search to identify the publications not indexed in the bibliographic databases in August 2020 and June 2021. We extracted quantitative data using a standardized data extraction form and summarized it using descriptive statistics. Additionally, we conducted thematic qualitative analyses and presented our findings as narrative summaries. Results: Included in our review were 54 records published between 1988 and 2021, of which 18 (33.3%) were peer-reviewed articles. The majority of reported populations were people with advanced HIV (n = 39, 72.2%) who use alcohol (n = 25, 46.3%) during HIV (n = 40, 74.1%) and COVID-19 (n = 15, 27.8%) outbreaks. Palliative care outcomes were heterogeneous but fell into four themes: 1) intervention (e.g., symptom management), 2) access (e.g., financial barriers), 3) clinical program (e.g., interdisciplinary collaboration), and 4) policy/guideline (e.g., drug regulations). Conclusions: Strategies and interventions can be implemented during communicable disease outbreaks to promote equitable access to palliative care by people who use substances.

Rational Pharmacotherapy in Infectious Diseases: Issues Related to Drug Residues in Edible Animal Tissues.

Drugs are used in veterinary medicine to prevent or treat animal diseases. When rationally administered to livestock following Good Veterinary Practices (GVP), they greatly contribute to improving the production of food of animal origin. Since humans can be exposed chronically to veterinary drugs through the diet, residues in food are evaluated for effects following chronic exposures. Parameters such as an acceptable daily intake (ADI), the no-observed-adverse-effect level (NOAEL), maximum residue limits (MRLs), and the withdrawal periods (WPs) are determined for each drug used in livestock. Drug residues in food exceeding the MRLs usually appear when failing the GVP application. Different factors related either to the treated animal or to the type of drug administration, and even the type of cooking can affect the level of residues in edible tissues. Residues above the MRLs can have a diverse negative impact, mainly on the consumer's health, and favor antimicrobial resistance (AMR). Drug residue monitoring programmes are crucial to ensure that prohibited or authorized substances do not exceed MRLs. This comprehensive review article addresses different aspects of drug residues in edible tissues produced as food for human consumption and provides relevant information contributing to rational pharmacotherapy in food-producing animals.

Applying lessons from the Ebola vaccine experience for SARS-CoV-2 and other epidemic pathogens.

The world is experiencing an unprecedented global pandemic of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2). Development of new vaccines and therapeutics are important to achieve long-term prevention and control of the virus. Experience gained in the development of vaccines for Ebola virus disease provide important lessons in the regulatory, clinical, and manufacturing process that can be applied to SARS-CoV-2 and other epidemic pathogens. This report outlines the main lessons learned by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD) during development of an Ebola Zaire vaccine (ERVEBO®) and looks ahead to critical lessons beyond vaccine development. It highlights focus areas for public-private partnership and regulatory harmonization that can be directly applied to current vaccine development efforts for SARS-CoV-2, while drawing attention to the need for parallel consideration of issues beyond development that are equally important to achieve global preparedness and response goals.