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Vaccine Apr 2017This article reviews the off-label recommendations and use of vaccines, and focuses on the differences between the labelled instructions on how to use the vaccine as... (Review)
Review
This article reviews the off-label recommendations and use of vaccines, and focuses on the differences between the labelled instructions on how to use the vaccine as approved by the regulatory authorities (or "label"), and the recommendations for use issued by public health advisory bodies at national and international levels. Differences between public health recommendations and the product label regarding the vaccine use can lead to confusion at the level of vaccinators and vaccinees and possibly result in lower compliance with national vaccination schedules. In particular, in many countries, the label may contain regulatory restrictions and warnings against vaccination of specific population groups (e.g. pregnant women) due to a lack of evidence of safety from controlled trials at the time of initial licensure of the vaccine, while public health authorities may recommend the same vaccine for that group, based on additional post-marketing data and benefit risk analyses. We provide an overview of the different responsibilities between regulatory authorities and public health advisory bodies, and the rationale for off-label use of vaccines, the challenges involved based on the impact of off-label use in real-life. We propose to reduce off-label use of vaccines by requiring the manufacturer to regularly adapt the label as much as possible to the public health needs as supported by new evidence. This would require manufacturers to collect and report post-marketing data, communicate them to all stakeholders and regulators to extrapolate existing evidence (when acceptable) to other groups or to other brands of a vaccine (class effect). Regulatory authorities have a key role to play by requesting additional post-marketing data, e.g. in specific target groups. When public health recommendations for vaccine use that are outside labelled indications are considered necessary, good communication between regulatory bodies, public health authorities, companies and health care providers or vaccinators is crucial. Recommendations as well as labels and label changes should be evidence-based. The rationale for the discrepancy and the recommended off-label use of a vaccine should be communicated to providers.
Topics: Drug Approval; Humans; Off-Label Use; Product Surveillance, Postmarketing; Vaccines
PubMed: 28341112
DOI: 10.1016/j.vaccine.2017.02.056 -
The Journal of Pharmacy Technology :... Feb 2022Professional regulatory authorities play a critical role in protecting public interest. Yet, there is a growing view that trust in regulatory authorities may be on the...
Professional regulatory authorities play a critical role in protecting public interest. Yet, there is a growing view that trust in regulatory authorities may be on the decline. Awareness has been identified as important for maintaining trust. However, research that examines public awareness and trust in pharmacy regulatory authorities (PRAs) is lacking. This research explores public awareness and trust of PRAs and presents recommendations to enhance PRA communication strategies. An online survey was conducted with the Nova Scotia (Canada) public in 2020. Adopting classifications from the Communications literature, 3 media generations were explored: newspaper, television, and the Internet. The χ test of independence and Kruskal-Wallis test were adopted to explore differences between the generations. Six hundred sixty-two usable surveys were obtained. Over 80% of those surveyed were aware of the existence of the PRA. Those who had heard of the PRA were most aware of its operational responsibilities and less aware of its governance. The Internet Generation was more aware that the PRA includes members of the public in its decision making than expected and showed increased trust toward the PRA versus the other media generations. The findings should help inform PRA communication plans and set baselines to assess whether such plans enhance awareness. Future studies should explore additional aspects of PRA awareness and trust, perform comparisons across pharmacy jurisdictions, and develop and test models of the relationship between PRA awareness and various dimensions of institutional trust.
PubMed: 35141726
DOI: 10.1177/87551225211051593 -
Frontiers in Medicine 2022The field of regulatory affairs deals with the regulatory requirements for marketing authorization of therapeutic products. This field is facing a myriad of forces... (Review)
Review
The field of regulatory affairs deals with the regulatory requirements for marketing authorization of therapeutic products. This field is facing a myriad of forces impacting all aspects of the development, regulation and value proposition of new therapeutic products. Changes in global megatrends, such as geopolitical shifts and the rise of the green economy, have emphasized the importance of manufacturing and supply chain security, and reducing the environmental impacts of product development. Rapid changes due to advances in science, digital disruption, a renewed focus on the centrality of the patient in all stages of therapeutic product development and greater collaboration between national regulatory authorities have been accelerated by the COVID-19 pandemic. This article will discuss the various trends that are impacting the development of new therapies for alleviating disease and how these trends therefore impact on the role of the regulatory affairs professional. We discuss some of the challenges and provide insights for the regulatory professional to remain at the forefront of these trends and prepare for their impacts on their work.
PubMed: 36698838
DOI: 10.3389/fmed.2022.1082384 -
Clinical Microbiology and Infection :... Sep 2022Oral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization for the treatment of mild-to-moderate COVID-19... (Review)
Review
BACKGROUND
Oral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization for the treatment of mild-to-moderate COVID-19 in non-hospitalized patients who are at high risk for clinical progression.
OBJECTIVES
To provide a clinical practice overview of first-generation oral antiviral agents against SARS-CoV-2.
SOURCES
References for this review were identified through searches of PubMed, Google Scholar, bioRxiv, medRxiv, regulatory drug agencies, and pharmaceutical companies' websites up to 16 February 2022.
CONTENT
Molnupiravir and nirmatrelvir and ritonavir have been authorized for use in nonhospitalized individuals with mild-to-moderate COVID-19 who are at high risk for progression. In clinical trials, molnupiravir reduced the frequency of hospitalization or death by 3% (relative risk reduction 30%), and nirmatrelvir and ritonavir by 6% (relative risk reduction 89%). Their use in clinical practice requires early administration, review of drug-drug interactions (nirmatrelvir and ritonavir), considerations of embryo-fetal toxicity (molnupiravir), and compliance with ingestion of a high number of pills. Knowledge gaps include the efficacy of these agents in vaccinated, hospitalized, or immunosuppressed individuals with prolonged SARS-CoV-2 persistence.
IMPLICATIONS
First-generation oral antivirals represent progress in therapeutics against SARS-CoV-2, but also pose new challenges in clinical practice. Further advances in the development of new drugs are required.
Topics: Antiviral Agents; Cytidine; Humans; Hydroxylamines; Pharmaceutical Preparations; Ritonavir; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35545195
DOI: 10.1016/j.cmi.2022.04.015 -
Neurology and Therapy Dec 2017Economic sustainability is of paramount importance in the rapidly evolving therapeutic scenario of multiple sclerosis (MS). Glatiramoids are a class of drugs whose... (Review)
Review
Economic sustainability is of paramount importance in the rapidly evolving therapeutic scenario of multiple sclerosis (MS). Glatiramoids are a class of drugs whose forefather, glatiramer acetate, has been used as a disease modifying drug (DMD) in patients with MS for over 20 years. Its patent expired in 2015; new versions of such drug are nowadays available on the market, potentially contributing to lowering prices and enhancing a better allocation of economic resources. In this review, we analyze the recommendations underlying the approval of both generic drugs and biosimilars by regulatory authorities, and we provide methodological tools to contextualize the design of studies on these new classes of drugs. We examine in more detail the preclinical and clinical data of Copemyl, a new member of the glatiramoid class, focusing on its biological and immunological properties and illustrating randomized controlled trials that led to its authorization.
PubMed: 28762192
DOI: 10.1007/s40120-017-0079-3 -
Allergologie Select 2023Allergen immunotherapy (AIT) has been performed for 112 years. In this article we summarize regulatory standards and challenges based on scientific evidence on AIT. Most... (Review)
Review
Allergen immunotherapy (AIT) has been performed for 112 years. In this article we summarize regulatory standards and challenges based on scientific evidence on AIT. Most crucial and timely aspects concerning AIT are addressed from the regulatory perspective of the authors as employees of a national competent authority in Europe: (1) product specificity; (2) clinical efficacy; (3) treatment for adults and children (needs for extrapolation); (4) allergen exposure chambers; (5) biomarkers; (6) standardization; (7) real-world evidence; (8) independent official batch release (benefit and challenges); (9) harmonization on the EU level. The Paul-Ehrlich-Institut (PEI), the Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main in Germany, examines and evaluates the benefits and risks of AIT products within the course of clinical development, marketing authorization, and subsequently throughout their entire life cycle to ensure high-quality, safe, and effective AIT products.
PubMed: 38143937
DOI: 10.5414/ALX02413E -
Investigative Radiology Jan 2020The purpose of this manuscript is to review the successive regulatory actions and decisions following the initial publication by Kanda and colleagues in 2014 regarding... (Review)
Review
OBJECTIVES
The purpose of this manuscript is to review the successive regulatory actions and decisions following the initial publication by Kanda and colleagues in 2014 regarding gadolinium retention in the human brain after multiple gadolinium-based contrast agents (GBCAs) administrations.
MATERIALS AND METHODS
Starting from 2014, the actions and decisions made by all regulatory authorities were collected and summarized region by region. Volumes of GBCA sales in 2018 per region and main countries are also presented as an indicator of patients' exposure to those products.
RESULTS
All regulatory authorities agreed on the absence of evidence of any harmful effect of gadolinium retention in humans. However, based on the same amount of preclinical and clinical evidence available in adults and children, regulatory authorities used different approaches resulting in different actions and decisions regarding the labeling and market authorizations of GBCAs, as well as the specific actions requested to the manufacturers.
CONCLUSIONS
The manufacturers of GBCAs had to face different situations according to the countries, due to the different positions and expectations from regulatory agencies. They have adapted their responses to the different positions of the regulatory agencies and conducted specific preclinical and clinical investigations to provide the expected evidence. It is also their responsibility to continuously monitor the benefit-risk balance of the products and to propose risk minimization measures to the regulatory agencies.
Topics: Adult; Brain; Child; Contrast Media; Drug Hypersensitivity; Female; Gadolinium; Health Policy; Humans; Internationality; Male; Patient Safety
PubMed: 31725063
DOI: 10.1097/RLI.0000000000000605 -
Frontiers in Plant Science 2019This chapter provides an in-depth discussion of the legal and regulatory frameworks surrounding cannabis in the United States, including federal law-as dictated by the... (Review)
Review
This chapter provides an in-depth discussion of the legal and regulatory frameworks surrounding cannabis in the United States, including federal law-as dictated by the Controlled Substances Act (CSA) and governed by various federal agencies like the FDA and DEA-as well as state law-as regulated by each state's laws and regulations authorizing medical and/or adult use cannabis. First, the chapter discusses the definition and classification of cannabis under the CSA, including scheduling under the CSA as well as the process for and potentiality of removing cannabis from Schedule I. Then, it describes the activities relating to industrial hemp that are permitted under the 2014 and 2018 Farm Bill. Next, the chapter addresses state-level cannabis laws. The chapter also analyzes the question of whether state cannabis laws are invalidated and superseded by federal law. Moreover, this section examines the factors underlying the extent of the Department of Justice's enforcement actions relating to state-authorized cannabis activities. The chapter then turns to CBD (cannabidiol) in particular, discussing CBD's legal status under the CSA; the FDA's role in regulating and approving CBD products for medical purposes; and the steps required to take an investigational CBD product through that approval process. The chapter concludes by contending that, while cannabis has had a long and twisting history, and although cannabis-derived products face daunting obstacles to achieving FDA approval as well as rescheduling under both federal and state law, the recent success of one product (Epidiolex) should inspire other manufacturers to develop additional cannabis-derived products through the FDA process.
PubMed: 31263468
DOI: 10.3389/fpls.2019.00697 -
Toxicology Communications 2020The media have featured the antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) to treat coronavirus (COVID-19). Political leaders have touted their use and...
The media have featured the antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) to treat coronavirus (COVID-19). Political leaders have touted their use and recommended availability to the public. These anti-inflammatory agents have substantial human toxicity with a narrow therapeutic window. CQ and HCQ poisoning cause myocardial depression and profound hypotension due to vasodilation. Bradycardia and ventricular escape rhythms arise from impaired myocardial automaticity and conductivity due to sodium and potassium channel blockade. With cardiotoxicity, ECGs may show widened QRS, atrioventricular heart block and QT interval prolongation. CQ may also cause seizures, often refractory to standard treatment. Of concern is pediatric poisoning, where 1-2 pills of CQ or HCQ can cause serious and potentially fatal toxicity in a toddler. The treatment of CQ/HCQ poisoning includes high-dose intravenous diazepam postulated to have positive ionotropic and antidysrhythmic properties that may antagonize the cardiotoxic effects of CQ. Infusions of epinephrine titrated to treat unstable hypotension, as well as potassium for severe hypokalemia may be required. Current scientific evidence does not support treatment or prophylactic use of these agents for COVID-19 disease. Regulatory and public health authorities recognize that CQ/HCQ may offer little clinical benefit and only add risk requiring further investigation before wider public distribution.
PubMed: 32457932
DOI: 10.1080/24734306.2020.1757967