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British Journal of Clinical Pharmacology Feb 2023Drug-related adverse reactions are among the main reasons for harm to patients under care worldwide and even their deaths. The pharmacovigilance system has been proven... (Review)
Review
Drug-related adverse reactions are among the main reasons for harm to patients under care worldwide and even their deaths. The pharmacovigilance system has been proven to be an effective method of avoiding or alleviating such adverse events. In 2019, after two decades of implementation of the drug-related adverse reaction reporting system, China formally implemented a pharmacovigilance system with the Pharmacovigilance Quality Management Standards and a series of supporting technical documents created to improve the safety of medication given to patients. China's pharmacovigilance system has faced many problems and challenges during its implementation. This spontaneous reporting system is the main source of data for China's medication vigilance activities, but it has not provided sufficiently powerful evidence for regulatory decision-making. In conformity with the health-centred drug regulatory concept, the Chinese government has accelerated the speed of examination and approval of urgently needed clinical drugs and orphan drugs along with the requirement to improve the safety supervision of these drugs after their listing. China's marketing authorization holders (MAHs) must strengthen their pharmacovigilance capabilities as the primary responsible departments for drug safety. Chinese medical schools generally lack professional courses on pharmacovigilance. The regulatory authorities have recognized such problems and have made efforts to improve the professional capacity of pharmacovigilance personnel and to strengthen cooperation with stakeholders through the implementation of an action plan of medication surveillance and the establishment of a patient-based adverse events reporting system and active surveillance systems, which will help China bridge the gap to bring its pharmacovigilance practice up to standards.
Topics: Humans; Pharmacovigilance; Adverse Drug Reaction Reporting Systems; Drug and Narcotic Control; China; Drug-Related Side Effects and Adverse Reactions
PubMed: 35165914
DOI: 10.1111/bcp.15277 -
Health Research Policy and Systems Apr 2021The World Health Organization 2019 WHO consolidated guideline on self-care interventions for health: sexual and reproductive health and rights includes recommendations... (Review)
Review
Regulatory standards and processes for over-the-counter availability of hormonal contraception and drugs for medical abortion in five countries in the Eastern Mediterranean Region.
The World Health Organization 2019 WHO consolidated guideline on self-care interventions for health: sexual and reproductive health and rights includes recommendations on self-administration of injectable contraception, over-the-counter (OTC) oral contraception and self-management of medical abortion. A review of the regulatory status of these two self-care interventions can highlight processes required to ensure that the quality of the medicines and safety of individuals are safeguarded in the introduction and scale-up in countries. This review outlines the legal regulatory status of prescription-only medicine (POM) and OTC contraceptives, including emergency contraception, and drugs for medical abortion in Egypt, Jordan, Lebanon, Morocco and Tunisia using information obtained from internet searches, regulatory information databases and personal contacts. In addition, the review examines whether the national medicines regulatory authorities have documented procedures available to allow for a change in status from a POM to OTC to allow for increased accessibility, availability and uptake of self-care interventions recommended by WHO. Egypt, Jordan and Lebanon have a documented national OTC list available. The only contraceptive product mentioned in the OTC lists across all five countries is ellaOne (ulipristal acetate for emergency contraception), which is publicly registered in Lebanon. None of the five countries has an official documented procedure to apply for the change of POM to OTC. Informal procedures exist, such as the ability to apply to the national medicines regulatory authority for OTC status if the product has OTC status in the original country of manufacture. However, many of these procedures are not officially documented, highlighting the need for establishing sound, affordable and effective regulation of medical products as an important part of health system strengthening. From a public health perspective, it would be advantageous for licensed products to be available OTC. This is particularly the case for settings where the health system is under-resourced or over-stretched due to health emergencies. Readiness of national regulatory guidelines and OTC procedures could lead to increased access, availability and usage of essential self-care interventions for sexual and reproductive health and rights.
Topics: Female; Hormonal Contraception; Humans; Lebanon; Mediterranean Region; Morocco; Pharmaceutical Preparations; Pregnancy
PubMed: 33882941
DOI: 10.1186/s12961-020-00661-2 -
La Revue de Medecine Interne Feb 2020In France, clinical research involving human beings is regulated by the Jardé's law since November 2016. The law distinguishes interventional and non-interventional... (Review)
Review
In France, clinical research involving human beings is regulated by the Jardé's law since November 2016. The law distinguishes interventional and non-interventional studies. Both need to be authorized by a Persons Protection Committee. Studies performed on medical data collected during standard clinical care are not considered as studies involving human beings. Medical data are personal data. French Data Protection Authority National has an important role, guarantying the respect of regulation on personal data. We summarize in this article the different types of studies and the role of regulatory authorities.
Topics: Biomedical Research; Computer Security; France; Government Regulation; Humans; Medical Records; Patient Rights
PubMed: 31898997
DOI: 10.1016/j.revmed.2019.11.009 -
Human Vaccines & Immunotherapeutics Dec 2024The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to urgent actions by innovators, vaccine developers, regulators, and other... (Review)
Review
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to urgent actions by innovators, vaccine developers, regulators, and other stakeholders to ensure public access to protective vaccines while maintaining regulatory agency standards. Although development timelines for vaccines against SARS-CoV-2 were much quicker than standard vaccine development timelines, regulatory requirements for efficacy and safety evaluations, including the volume and quality of data collected, were upheld. Rolling review processes supported by sponsors and regulatory authorities enabled rapid assessment of clinical data as well as emergency use authorization. Post-authorization and pharmacovigilance activities enabled the quantity and breadth of post-marketing safety information to quickly exceed that generated from clinical trials. This paper reviews safety and reactogenicity data for the BNT162 vaccine candidates, including BNT162b2 (Comirnaty, Pfizer/BioNTech COVID-19 vaccine) and bivalent variant-adapted BNT162b2 vaccines, from preclinical studies, clinical trials, post-marketing surveillance, and real-world studies, including an unprecedentedly large body of independent evidence.
Topics: Humans; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Marketing; Pharmacovigilance; SARS-CoV-2; Vaccines, Combined
PubMed: 38407186
DOI: 10.1080/21645515.2024.2315659 -
The Journal of Molecular Diagnostics :... Oct 2021The coronavirus disease 2019 (COVID-19) response necessitated innovations and a series of regulatory deviations that also affected laboratory-developed tests (LDTs). To... (Review)
Review
Temporary Regulatory Deviations and the Coronavirus Disease 2019 (COVID-19) PCR Labeling Update Study Indicate What Laboratory-Developed Test Regulation by the US Food and Drug Administration (FDA) Could Look Like.
The coronavirus disease 2019 (COVID-19) response necessitated innovations and a series of regulatory deviations that also affected laboratory-developed tests (LDTs). To examine real-world consequences and specify regulatory paradigm shifts, legislative proposals were aligned on a common timeline with Emergency Use Authorization (EUA) of LDTs and the US Food and Drug Administration (FDA)-orchestrated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) labeling update study. The initial EUA adoption by LDT developers shows that the FDA can have oversight over LDTs. We used efficiency-corrected microcosting of our EUA PCR assay to estimate the national cost of the labeling update study to $0.3 to $1.4 million US dollars. Labeling update study performance data showed lower average detection limits in commercial in vitro diagnostic (IVD) assays versus LDTs (32,000 ± 75,000 versus 71,000 ± 147,000 nucleic acid amplification tests/mL; P = 0.04); however, comparison also shows that FDA review of IVD assays and LDTs did not prevent differences between initial and labeling update performance (IVD assay, P < 0.0001; LDT, P = 0.003). The regulatory shifts re-emphasized that both commercial tests and LDTs rely heavily on laboratory competence and procedures; however, lack of performance data on authorized tests, when clinically implemented, precludes assessment of the benefit related to regulatory review. Temporary regulatory deviations during the pandemic and regulatory science tools (ie, reference material) have generated valuable real-world evidence to inform pending legislation regarding LDT regulation.
Topics: COVID-19 Nucleic Acid Testing; Humans; Laboratories; Limit of Detection; Polymerase Chain Reaction; Time Factors; United States; United States Food and Drug Administration
PubMed: 34538703
DOI: 10.1016/j.jmoldx.2021.07.011 -
Brain Tumor Research and Treatment Jul 2023The three-dimensional (3D) printing itself is not a novel technology, it is more than 30 years old. Stereolithographic (SLA) technology has been used as the first and... (Review)
Review
The three-dimensional (3D) printing itself is not a novel technology, it is more than 30 years old. Stereolithographic (SLA) technology has been used as the first and popular technology for medical application of 3D printing. Since 1991 and have published articles about SLA for rapid prototyping anatomical 3D models. Medical applications of 3D printing have been popularizing and stabilizing so far. Implantable medical devices such as metal or absorbable implants, surgical guide systems, prosthesis and orthosis, and 3D anatomical models for normal or diseased anatomy have been developing and expanding its markets so far. There are many obstacles, such as insurance, authorization as a medical device, and lack of standards technology for further expansion of medical applications. Many technical specifications and guidelines for authorization as medical device have been published by regulatory bodies from many countries. Even though international standards for 3D printing have been developing more and more, there have been few standards for medical application of 3D printing. In this harsh environment academia, company, research institute, regulatory bodies, and government have been doing good job for the development of 3D printing industry.
PubMed: 37550814
DOI: 10.14791/btrt.2023.0001 -
Combinatorial Chemistry & High... 2022The modern pharmaceutical industry is transitioning from traditional methods to advanced technologies like artificial intelligence. In the current scenario, continuous... (Review)
Review
The modern pharmaceutical industry is transitioning from traditional methods to advanced technologies like artificial intelligence. In the current scenario, continuous efforts are being made to incorporate computational modeling and simulation in drug discovery, development, design, and optimization. With the advancement in technology and modernization, many pharmaceutical companies are approaching in silico trials to develop safe and efficacious medicinal products. To obtain marketing authorization for a medicinal product from the concerned National Regulatory Authority, manufacturers must provide evidence for the safety, efficacy, and quality of medical products in the form of in vitro or in vivo methods. However, more recently, this evidence was provided to regulatory agencies in the form of modeling and simulation, i.e., in silico evidence. Such evidence (computational or experimental) will only be accepted by the regulatory authorities if it considered as qualified by them, and this will require the assessment of the overall credibility of the method. One must consider the scrutiny provided by the regulatory authority to develop or use the new in silico evidence. The United States Food and Drug Administration and European Medicines Agency are the two regulatory agencies in the world that accept and encourage the use of modeling and simulation within the regulatory process. More efforts must be made by other regulatory agencies worldwide to incorporate such new evidence, i.e., modeling and simulation (in silico) within the regulatory process. This review article focuses on the approaches of in silico trials, the verification, validation, and uncertainty quantification involved in the regulatory evaluation of biomedical products that utilize predictive models.
Topics: Artificial Intelligence; Computer Simulation; Drug Industry; Pharmaceutical Preparations; United States; United States Food and Drug Administration
PubMed: 34986768
DOI: 10.2174/1386207325666220105150147 -
Expert Review of Anti-infective Therapy 2023Since the beginning of the COVID-19 pandemic, the repurposing of medicines has been pursued to find interventions effective in preventing fatal outcome of the disease....
INTRODUCTION
Since the beginning of the COVID-19 pandemic, the repurposing of medicines has been pursued to find interventions effective in preventing fatal outcome of the disease. One of these drugs was tocilizumab, an interleukin-6 inhibiting monoclonal antibody, previously used to treat several immune-related disorders.
AREAS COVERED
In this article, we present the results of the initial observational studies and subsequent randomized clinical trials on the efficacy and safety of tocilizumab in the treatment of COVID-19. Despite conflicting results, possibly due to the heterogeneity of the studied populations, large studies have ultimately proven that preventing IL-6 from attaching to its receptors can effectively reverse the fatal course of the disease. We also discuss the meta-analyses, which mostly supported the validity of tocilizumab therapy. We show how tocilizumab found its place in the most important recommendations on COVID-19 treatment and obtained authorization from the major regulatory authorities.
EXPERT OPINION
The criteria for optimizing tocilizumab therapy in COVID-19 still need to be established. They are also important considering the existing risks of future zoonotic spillovers and epidemics that may trigger hyperinflammation that could be efficiently blocked. The experience gained with tocilizumab shall be perceived as preparedness for future challenges.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Drug Treatment; Pandemics; Treatment Outcome
PubMed: 37326214
DOI: 10.1080/14787210.2023.2226867 -
Autonomic Neuroscience : Basic &... Nov 2021Gefapixant is the approved generic name for a compound also known as MK-7264, and prior to that AF-219 and RO-4926219. It is the first-in-class clinically developed...
Gefapixant is the approved generic name for a compound also known as MK-7264, and prior to that AF-219 and RO-4926219. It is the first-in-class clinically developed antagonist for the P2X3 subtype of trimeric ionotropic purinergic receptors, a family of ATP-gated excitatory ion channels, showing nanomolar potency for the human P2X3 homotrimeric channel and essentially no activity at related channels devoid of P2X3 subunits. As the first P2X3 antagonist to have progressed into clinical studies it has now progressed to the point of successful completion of Phase 3 investigations for the treatment of cough, and the NDA application is under review with US FDA for treatment of refractory chronic cough or unexplained chronic cough. The molecule was discovered in the laboratories of Roche Pharmaceuticals in Palo Alto, California, but clinical development then continued with the formation of Afferent Pharmaceuticals for the purpose of identifying the optimal therapeutic indication for this novel mechanism and establishing a clinical plan for development in the optimal patient populations selected. Geoff Burnstock was a close collaborator and advisor to the P2X3 program for close to two decades of discovery and development. Progression of gefapixant through later stage clinical studies has been conducted by the research laboratories of Merck & Co., Inc., Kenilworth, NJ, USA (MRL; following acquisition of Afferent in 2016), who may commercialize the product once authorization has been granted by regulatory authorities.
Topics: Adenosine Triphosphate; Cough; Humans; Purinergic P2X Receptor Antagonists; Pyrimidines; Receptors, Purinergic P2X3; Sulfonamides
PubMed: 34403981
DOI: 10.1016/j.autneu.2021.102859 -
European Journal of Pharmaceutics and... Sep 2022The emergence of innovator-driven complex drug products, such as Non-Biological Complex Drugs (NBCDs), has provided disruptive advances in the Nanotechnology and... (Review)
Review
The emergence of innovator-driven complex drug products, such as Non-Biological Complex Drugs (NBCDs), has provided disruptive advances in the Nanotechnology and Biotechnology fields. However, the design and development of NBCDs can be particularly challenging due to some unresolved scientific and regulatory challenges associated with the pharmaceutical quality assessment. The application of a more holistic, systematic, integrated science and risk-based approach, such as Quality by Design (QbD), is essential to address key scientific, technological, and regulatory constraints in the research and development of the NBCDs. The deeper product and process understanding derived from the implementation of the QbD approach ensures consistent, reliable, and high-quality pharmaceutical products. Furthermore, this approach promotes innovation and continuous improvement in the entire product lifecycle. Regulatory authorities highly recommend QbD-based submissions to successfully translate NBCDs from laboratory-scale research to the pharmaceutical market with the required quality, safety, and efficacy standards. The main aim of this article is to obtain a comprehensive and in-depth investigation into the state of implementation of the QbD approach in the pharmaceutical development and marketing authorization of NBCDs in Europe and the United States, through the analysis of the available data from their regulatory dossiers. In addition, it aims to understand and discuss how the QbD approach is used and implemented for complex drug products in the pharmaceutical industry, highlighting the gaps and challenges involved with its implementation. An analysis is held regarding QbD's advantages in terms of knowledge growth, regulatory flexibility, and the speed of development based on big data science, along with the reduction of regulatory failures and market withdrawals.
Topics: Biological Products; Biotechnology; Drug Industry; Marketing
PubMed: 35908664
DOI: 10.1016/j.ejpb.2022.07.014