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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 -
Journal of Cutaneous Medicine and... 2022Soft Tissue Filler (STF) Therapy for cosmetic facial rejuvenation is associated with known complications. The manifestation of these known complications can lead to... (Review)
Review
Soft Tissue Filler (STF) Therapy for cosmetic facial rejuvenation is associated with known complications. The manifestation of these known complications can lead to patients commencing civil litigation actions or making complaints to provincial regulatory authorities and alleging that the practitioner failed to obtain the patient's informed consent to the therapy. Data provided by the Canadian Medical Protective Association (CMPA) on medical-legal cases arising from the provision of STF therapy between 2005 and 2019 are presented. Select reported case law decisions from Canadian courts and regulatory bodies addressing the concept of informed consent are reviewed. Insights about the risk factors pertaining to the process of obtaining informed consent for STF therapy are presented to increase an understanding of the elements of communication and documentation needed to ensure patients are aware of the consequences of this treatment.
Topics: Canada; Cosmetic Techniques; Dermal Fillers; Face; Humans; Informed Consent; Malpractice
PubMed: 34310242
DOI: 10.1177/12034754211032542 -
Diabetes Technology & Therapeutics Jul 2015Insulin analog patent expiry is likely to mean that, increasingly, copies of original biopharmaceutical products will be submitted for authorization. Experience with... (Review)
Review
Insulin analog patent expiry is likely to mean that, increasingly, copies of original biopharmaceutical products will be submitted for authorization. Experience with biosimilars in other therapeutic areas suggests that careful regulation and caution are needed. Published guidelines of regulatory authorities around the world on approval of biosimilars and, where available, insulin biosimilars were reviewed. Information was sourced through Internet searching and cross-referencing guidelines. As of August 2014, general biosimilar and insulin-specific guidelines are available in 34 countries and two countries/regulatory domains, respectively. Many guidelines are clearly related to, or partly derived from, the general and insulin-specific European Medicines Agency (EMA) guidelines. Areas covered by these guidelines are fairly consistent, covering preclinical, pharmacokinetic (PK), and pharmacodynamic (PD) studies in humans and clinical areas; however, there are differences in emphasis. The EMA insulin-specific guidelines include detailed criteria on PK/PD studies, as do most other general biosimilar guidelines and, to a lesser extent, clinical studies. The U.S. Food and Drug Administration has general biosimilar guidelines, emphasizing consideration of the whole package of in vitro, biological, and human studies, rather than concentrating on any one aspect. In countries such as Mexico, guidelines are broad, leaving wide discretion to the regulatory authority. In conclusion, from a global perspective, this area of drug regulation is heterogeneous and evolving, and the authors call for an initiative aimed at harmonizing the requirements for biosimilar insulins.
Topics: Biosimilar Pharmaceuticals; Drug Approval; Europe; Humans; Insulins; Mexico; United States; United States Food and Drug Administration
PubMed: 25789689
DOI: 10.1089/dia.2014.0362 -
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 -
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 -
Current Medicinal Chemistry 2021The translation of nanomedicines from the lab level into marketed product faces several challenges, including characterization of physicochemical properties,...
The translation of nanomedicines from the lab level into marketed product faces several challenges, including characterization of physicochemical properties, pharmacodynamics, pharmacokinetics, process control, biocompatibility, and nanotoxicity, scaling-up as well as reproducibility. The challenges of nanomedicine development are in connection with the different requirements from the patient (clinical and therapeutic use), industry (production), and regulatory bodies (authorization process). This paper aims at reviewing the status and regulatory aspects of nano-based drug delivery systems with a focus on the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) regulations. In addition to discussing the risks accompanied by the development of nanomedicine, the potential of following a risk-based methodology from the early stage of the R&D phase is emphasized here to ensure safety and efficacy when developing novel nano-based dosage forms. The R&D of nanomedicines is a complex and multidisciplinary approach, and there are still many challenges in their regulation and legislation. In general, the most critical considerations for nanomedicines are the product quality assessment (physicochemical characteristics, quality control, manufacturing process) and product safety assessment (pharmacokinetics, biodegradation, accumulation, and nanotoxicity). The paper presents a promising paradigm in the development and marketing authorization of nanomedicines, namely the Quality by Design (QbD) approach. Sufficient knowledge on the quality, safety, and efficacy of nanomedicines is necessary to obtain a significant focus on establishing robust, standardized methods for evaluating the critical quality attributes of nanomedicines. The QbD-based submission is highly recommended and required by the regulatory authorities, enabling a smooth clinical translation of the novel nanomedicines.
Topics: Humans; Nanomedicine; Reproducibility of Results; United States
PubMed: 33823761
DOI: 10.2174/0929867328666210406115529 -
Therapeutic Innovation & Regulatory... Mar 2024This qualitative study aims to analyze current PM regulation and market access requirements and proposes potential solutions to mitigate current challenges.
OBJECTIVES
This qualitative study aims to analyze current PM regulation and market access requirements and proposes potential solutions to mitigate current challenges.
METHODS
Twenty-two semi-structured interviews were conducted with experts from pharmaceutical industry, regulatory authorities, national health technology assessment (HTA) bodies, pediatricians, and academia from the Netherlands (NL), Germany (DE), the United Kingdom (UK), and France (FR) to get insight into the pediatric research, the regulatory and reimbursement processes, challenges, and solutions. Themes for further testing were developed on how to facilitate pediatric market access. Atlas.ti 9 was used to analyze the findings.
RESULTS
Heterogeneity in requirements for the European Medicines Agency (EMA) and HTA approvals are noted. By example, DE grants direct reimbursement after regulatory approval, the other countries require additional reimbursement which generate delays and challenges in patient access after marketing authorization. Key components in facilitating PM market access include multi-stakeholder collaboration, transparency, patient representatives, informed consent guidance, real-world evidence, and appropriate clinical trial designs. Pricing models based on the economic capabilities of individual countries could further reduce delays and challenges in market access. The additional specific pediatric incentives should be taken as best practice to encourage innovation in pediatric conditions.
CONCLUSION
This study highlights differences in requirements for regulatory and reimbursement approval, along with international differences in pricing and reimbursement procedures for pediatric market access.
Topics: Child; Humans; Costs and Cost Analysis; Germany; United Kingdom; Qualitative Research
PubMed: 38172379
DOI: 10.1007/s43441-023-00601-6 -
Heliyon Jul 2023Cities in the global south, constrained by limited resources, face challenges in delivering efficient transportation infrastructure and services to support their rapidly... (Review)
Review
Cities in the global south, constrained by limited resources, face challenges in delivering efficient transportation infrastructure and services to support their rapidly growing urban populations. Dhaka, serves as an example, as it grapples with the increasing demand driven by population growth, exacerbated by factors like land and resource scarcity, as well as intricate geopolitical dynamics. Despite the construction of a metro rail and other similar mass transit options, Dhaka continues to face difficulties in meeting the increasing transportation demand, posing a persistent challenge. Multiple institutions, including a coordination authority, are working to provide improved transportation services by implementing diverse strategic approaches focusing on infrastructure development, and formulating policies aimed at facilitating better mobility and accessibility. Over the past fifty years, the institutional arrangement and roles within the transportation system have changed. This study examines the institutional arrangements and how they have evolved, along with reviewing transportation development policies during this period. The findings indicate the involvement of multiple organizations in the city's transportation system performing distinct activities-- administrative, coordinating, legislative, regulatory, construction and management, and law enforcement. These authorities often encounter challenges fulfilling their responsibilities stemming from differences in vision, organizational structure, jurisdiction and most notably, lack of coordinatoon, resulting in ineffective infrastructure development and duplicated activities. To improve the transportation system, this study recommends better equipping the existing coordinating authority and expanding its jurisdiction to include other institutions. This approach aims to enhance coordination and address the challenges faced by Dhaka's transportation system, ultimately facilitating improved mobility and accessibility for the city's growing population.
PubMed: 37456001
DOI: 10.1016/j.heliyon.2023.e17887 -
Advanced Drug Delivery Reviews Jun 2018Nanomedicines and follow-on versions (also called nanosimilars in the EU) have been on the market partially for decades although without recognition of their nano... (Review)
Review
Nanomedicines and follow-on versions (also called nanosimilars in the EU) have been on the market partially for decades although without recognition of their nano properties in the beginning; a substantial number is in clinical development. Nanomedicines are typically synthetic and belong to the non-biological complex drugs. They show a high variability in form, structure, and size. Additionally large molecule biologics show nano-characteristics meaning nano-dimension in size (1-100 nm) or specific properties related to these dimensions. The high complexity of nanomedicines with their heterogeneous structures do not allow a full physicochemical quality characterization, challenging the regulatory evaluation especially for follow-on versions upon comparison with the reference product. The generic paradigm with the sameness approach for quality and bioequivalence in blood plasma is not appropriate for nanomedicines where a similar approach is needed. After experiencing non-equivalence of authorized parenteral colloidal iron follow-on versions, EMA and FDA issued reflection papers and draft guidances for industry to present their current thinking on the evaluation of such complex products. A stepwise approach to evaluate the extent of similarity, from quality, including critical quality attributes (CQA) and assessment of nano properties, to a non-clinical biodistribution assay, required in the the EU but not in the US, and to clinical evaluation makes sense. The cumulated totality of evidence for the authorization of nanomedicine follow-on versions goes case-by-case. Interchangeability, or substitutability, is a challenge. However, a defined or even harmonized approval pathway for these follow-versions is still missing and causes potential differences in approval. To progress, a science-based discussion platform among stakeholders and experts in the field is necessary. An agenda has been agreed [5], namely CQA assessment, publication of scientific and clinical findings, consensus on nomenclature and labelling, and regulatory actions on substandard complex drug products. Consensus created in a public private approach will support progress towards a defined and harmonized regulatory pathway for nanomedicines and their follow-on versions. This will provide drug innovation but also larger access to follow-on versions of nanomedicines, both a benefit for the patient.
Topics: Drugs, Generic; Humans; Nanomedicine; Particle Size
PubMed: 29966685
DOI: 10.1016/j.addr.2018.06.024