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1.
Ther Innov Regul Sci ; 58(3): 433-442, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38369639

RESUMO

The complexity and inter-connectedness of operating in a global world for drug product supply has become an undeniable reality, further underscored by the COVID-19 pandemic. For Post-Approval Changes (PACs) that are an inevitable part of a product's commercial life, the impact of the growing global regulatory complexity and related drug shortages has brought the Global PAC Management System to an inflection point in particular for companies that have their products marketed in many countries.This paper illustrates through data analyzed for the first time from 145,000 + PACs for 156 countries, collected by 18 global pharma companies over a 3-year period (2019-2021), how severe the problem of global regulatory complexity is. Only PACs requiring national regulatory agency (NRA) approval prior to implementation were included in the data set. 1 of the 156 country NRAs approved all submitted PACs within a period of 6 months. The 6-month timeline was chosen because it is the recommended review timeline for major changes in the WHO guidance for vaccines and biotherapeutic products. 10 out of the 156 (6%) countries had no more than 10% of the PACs reviewed and approved in > 6 months. In 33 (22%) countries more than half of the PACs took > 6 months for approval. It is rare that the same PAC is approved globally within 6 months as individual NRAs take from a few months to years (in some cases > 5 years) for their review.The global PAC management complexity has steadily grown over the past 20 years. Attempts thus far to solve this problem have not made any meaningful difference. Senior leaders and decision-makers across the interdependent components of the complex Global PAC Management System (industry and regulators) must come together and collaboratively manage the problem holistically with the objective of ensuring global drug product availability instead of continuing with distinct stakeholder or country-focused solutions, which can tend to worsen the problem.In this paper, the Chief Quality Officers (CQOs) from 18 of the largest innovator pharma companies (see Acknowledgements) are speaking with One-Voice-of-Quality for PACs (1VQ for PACs Initiative). They are recommending a set of 8 approaches to activate a holistic transformation of the Global PAC Management System. This article presents their view on the problem of global regulatory complexity for managing PACs, it's impact on continual improvement and the risk to drug product supply, as well as approaches that can help alleviate the problem.


Assuntos
Aprovação de Drogas , Humanos , Aprovação de Drogas/organização & administração , COVID-19 , Indústria Farmacêutica/organização & administração , Indústria Farmacêutica/legislação & jurisprudência , Gestão de Mudança , Vigilância de Produtos Comercializados , SARS-CoV-2
2.
J Clin Pharmacol ; 61(10): 1261-1273, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33896027

RESUMO

In August 2020, the International Council on Harmonisation (ICH) released a new draft document, which for the first time combined nonclinical (S7B) and clinical (E14) Questions and Answers (Q&As) into 1 document. FDA describes the revision as a "value proposition": if the human ether-à-go-go assay and the in vivo study are performed in a standardized way, the number of dedicated thorough QT (TQT) studies can be reduced. In this article, we describe and discuss the Q&As that relate to clinical ECG evaluation. If supported by negative standardized nonclinical assays, Q&A 5.1 will obviate the need for a TQT study in the case that a >2-fold exposure margin vs high clinical scenario cannot be obtained. Q&A 6.1 addresses drugs that are poorly tolerated in healthy subjects and cannot be studied at high doses or in placebo-controlled studies; it therefore mainly applies to oncology drugs. It will enable sponsors to claim that a new drug has a "low likelihood of proarrhythmic effects" in the case that the mean corrected QT effect is <10 milliseconds at the time of market application. The E14 2015 revision allowed application of concentration-corrected QT analysis on data from routinely performed clinical pharmacology studies, for example, the first-in-human study and the proportion of dedicated TQT studies has since steadily decreased. It can be foreseen that the proposed new revision will further reduce the number of TQT studies. To achieve harmonization across regulatory regions, it seems important to reach consensus within the International Council on Harmonisation group on the new threshold proposed in 6.1. For this purpose, the Implementation Working Group has asked for public comments.


Assuntos
Aprovação de Drogas/organização & administração , Drogas em Investigação/efeitos adversos , Eletrocardiografia/normas , Ensaios Clínicos como Assunto/normas , Avaliação Pré-Clínica de Medicamentos/normas , União Europeia , Humanos , Modelos Biológicos , Estados Unidos , United States Food and Drug Administration/normas
3.
Clin Pharmacol Ther ; 109(4): 987-999, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33705574

RESUMO

In this paper, we review the key elements that should be considered to take a novel vaccine from the laboratory through to licensure in the modern era. This paper is divided into four sections. First, we discuss the host immune responses that we engage with vaccines. Second, we discuss how in vivo and in vitro studies can inform vaccine design. Third, we discuss different vaccine modalities that have been licensed or are in testing in humans. Last, we overview the basic principles of vaccine approvals. Throughout we provide real-world examples of vaccine development against infectious diseases, including coronavirus disease 2019 (COVID-19).


Assuntos
Aprovação de Drogas/organização & administração , Vacinas/imunologia , Adjuvantes Imunológicos/farmacologia , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Imunidade Coletiva/imunologia , Imunidade Inata/imunologia , Saúde Pública , Estados Unidos , United States Food and Drug Administration
4.
Clin Pharmacol Ther ; 109(4): 856-866, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33523464

RESUMO

The value of model-based translation in drug discovery and development is now effectively being recognized in many disease areas and among various stakeholders. Such quantitative approaches are expected to facilitate the selection on which compound to prioritize for successful development, predict the human efficacious dose based on preclinical data with adequate precision, guide design, and de-risk later development stages. The importance of time-dependencies, which are typically species-dependent due to different turnover rates of biological processes, is, however, often neglected. For bacterial infections, the choice of dosing regimen is typically relying on preclinical pharmacokinetic (PK) and pharmacodynamic (PD) data, because the bacterial load and disease severity, and consequently the PK/PD relationship, cannot be quantified well on clinical data, given the low-information end points used. It is time to recognize the limitations of using time-collapsed approaches for translation (i.e., methods where targets are based on summary measures of exposure and response). Models describing the full time-course captures important quantitative information of drug distribution, bacterial growth, antibiotic killing, and resistance development, and can account for species-differences in the PK profiles driving the killing. Furthermore, with a model-based approach for translation, we can take a holistic approach in development of a joint model for in vitro, in vivo, and clinical data, as well as incorporating information on the contribution of the immune system. Such advancements are anticipated to facilitate rational decision making during various stages of drug development and in the optimization of treatment regimens for different groups of patients.


Assuntos
Anti-Infecciosos/farmacologia , Desenvolvimento de Medicamentos/organização & administração , Modelos Biológicos , United States Food and Drug Administration/organização & administração , Aminoglicosídeos/farmacologia , Anti-Infecciosos/farmacocinética , Antivirais/farmacologia , Carbapenêmicos/farmacologia , Relação Dose-Resposta a Droga , Aprovação de Drogas/organização & administração , Descoberta de Drogas/organização & administração , Avaliação Pré-Clínica de Medicamentos/métodos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistência Microbiana a Medicamentos/fisiologia , Quimioterapia Combinada , Humanos , Nebramicina/análogos & derivados , Nebramicina/farmacologia , Projetos de Pesquisa , Estados Unidos , United States Food and Drug Administration/normas
7.
J Diet Suppl ; 17(5): 493-502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32543246

RESUMO

The proliferation in the last few years of cannabidiol (CBD)-containing products in the U.S. markets has been greatly accelerated by changes in the regulatory environment, and by perceptions of their health benefits and presumed safety. The result has been aggressive marketing of many types of products, some of dubious quality, making or implying drug-type claims. The recent approval by the U.S. Food and Drug Administration (FDA) of CBD in the form of Epidiolex®, further complicates the regulatory picture. In addition, a number of studies suggest that, at least at high doses, there may be serious adverse effects or drug interactions associated with CBD. At present, CBD-containing products do not meet the strict definition of dietary supplements, but the FDA is continuing to consider some framework under which they might be allowed. Meanwhile, FDA has adopted a "risk-based" enforcement policy. Possible approaches to a new framework for regulation of CBD products as dietary supplements are discussed here, including expanded research emphasis, a robust corporate stewardship program, and a rigorous adverse event reporting program.


Assuntos
Canabidiol/uso terapêutico , Suplementos Nutricionais , Aprovação de Drogas/organização & administração , United States Food and Drug Administration , Humanos , Estados Unidos
8.
Pharmacoepidemiol Drug Saf ; 29(10): 1325-1330, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32281186

RESUMO

PURPOSE: Internationally, there has been widespread medical use of cannabis medicines before rigorous evaluations in randomised controlled trials (RCTs). Some advocates of medicinal use of cannabis argue that real-world evidence (RWE) can be a substitute for or at least supplement evidence from RCTs. We explore the utility, limitations and impact of RWE in the translation of cannabis medicines research into clinical practice using the established literature. METHODS: A literature search was performed via Embase and Medline using a diverse range of cannabinoid and RWE search terms. The review provides a snapshot of cannabis medicine RWE initiatives from around the world. RESULTS: Diverse and novel sources of real-world data and RWE include international cannabis registries, surveys, post-marketing data collection and use of electronic or digital health records. The strengths and limitations of using RWE in translational research are highlighted, along with the identification of barriers to RCTs involving cannabis medicines. CONCLUSIONS: RWE promises to play a significant role in the evaluation of cannabis medicines around the world. When used appropriately RWE may complement RCT data by providing valuable insights into cannabis medicine safety and effectiveness. TAKE HOME MESSAGES: It is important that real-world evidence (RWE) is used to complement rather than replace randomised controlled trial (RCT) evidence on cannabis medicines. Technological advances have created the opportunity to explore diverse and novel sources of cannabis medicine RWE. Although RWE may be more reflective of real-world clinical practice, it cannot provide conclusive evidence of the safety and efficacy of cannabis medicines. While acknowledging its limitations, RWE may nonetheless provide some guidance on safety and adverse events of cannabis medicines. RWE has already had a significant impact on the regulation of cannabis medicines.


Assuntos
Dor Crônica/tratamento farmacológico , Aprovação de Drogas/organização & administração , Medicina Baseada em Evidências/estatística & dados numéricos , Maconha Medicinal/uso terapêutico , Aprovação de Drogas/estatística & dados numéricos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Medicina Baseada em Evidências/métodos , Humanos , Vigilância de Produtos Comercializados/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Resultado do Tratamento
10.
Therapie ; 73(6): 495-500, 2018 Dec.
Artigo em Francês | MEDLINE | ID: mdl-29680374

RESUMO

Intranasal naloxone aims at preventing opioid overdose related deaths in active drug users. In France, it has been available since July 2016 through a temporary approval which requires a hospital-based pharmacy and a nominative registration of each patient. We present the characteristics of the first patients who could receive this prescription in our hospital-based addiction center and how they used naloxone during follow-up. Results favor a larger dispensing of naloxone. Patients' as well as peers' and families' education is needed.


Assuntos
Medicina do Vício , Instituições de Assistência Ambulatorial , Aprovação de Drogas , Overdose de Drogas/tratamento farmacológico , Implementação de Plano de Saúde , Naloxona/administração & dosagem , Medicina do Vício/métodos , Medicina do Vício/organização & administração , Administração Intranasal , Adulto , Instituições de Assistência Ambulatorial/organização & administração , Instituições de Assistência Ambulatorial/normas , Comportamento Aditivo/tratamento farmacológico , Comportamento Aditivo/epidemiologia , Aprovação de Drogas/métodos , Aprovação de Drogas/organização & administração , Overdose de Drogas/mortalidade , Feminino , França/epidemiologia , Órgãos Governamentais/organização & administração , Órgãos Governamentais/normas , Implementação de Plano de Saúde/organização & administração , Implementação de Plano de Saúde/normas , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/organização & administração , Programas Nacionais de Saúde/normas , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Paris/epidemiologia , Padrões de Prática Médica/normas , Encaminhamento e Consulta/estatística & dados numéricos , Fatores de Tempo
12.
Eur J Intern Med ; 24(3): 217-21, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23279878

RESUMO

Unexpected drug interactions have led to the withdrawal of many drugs, raising concern about the gap between what is known at the time of approval and the risk of serious effects in the longer term, particularly in high-risk populations generally excluded from drug development. This is because the majority of drug interaction studies are done using in vitro methods, or in healthy young volunteers who may not reflect the complexity of patients, and the settings in which the drug will be used in clinical practice. Pre-marketing interaction studies should therefore be designed to make information easily accessible and clinically transferable. They should be adequate in terms of sample size, population, comorbidity, phenotyping and/or genotyping, end-points and outcome measures, and conducted in conditions of dose, route and timing of co-administration that reproduce the proposed therapeutic indications of the new drug. Although young volunteers have the advantage of minimizing some confounding effects introduced by diseases or polypharmacy, patients drawn from populations for whom the drug is intended would be more relevant and accurate, providing the studies are feasible and safe.


Assuntos
Avaliação Pré-Clínica de Medicamentos , Avaliação de Medicamentos , Interações Medicamentosas , Conduta do Tratamento Medicamentoso , Segurança do Paciente/normas , Aprovação de Drogas/métodos , Aprovação de Drogas/organização & administração , Avaliação de Medicamentos/classificação , Avaliação de Medicamentos/métodos , Avaliação de Medicamentos/normas , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/normas , Nível de Saúde , Humanos , Seleção de Pacientes
13.
Zhongguo Zhong Yao Za Zhi ; 37(15): 2333-7, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23193572

RESUMO

OBJECTIVE: To analyze reasons for disapproval of registration application of new traditional Chinese medicines in recent years and discuss potential problems occurring in R&D and registration administration of new traditional Chinese medicines in China. METHOD: All applications of new traditional Chinese medicines for registrations that had been disapproved by Center for Drug Evaluation of State Food Drug Administration from 2006 to 2008 were searched in data bank. Specific reasons for disapproval of each variety were inquired and sorted out. The statistics involved the proportion of each type (kind) disapproval reasons in all disapprovals in order to analyze which were the main reasons. The results were analyzed to find out potential problems occurring in R&D and registration administration of new traditional Chinese medicines in China. RESULT: There were totally 247 disapproved registration applications for new traditional Chinese medicines. Among them, there were 218 applications for clinical trials and 29 applications for launch in the market There were 9 categories (29 types) of reasons for the applications for clinical trials applications, mainly including such problems as R&D proposal, non-clinical effectiveness and non-clinical safety; while there were 5 categories (9 types) of reasons for the applications for launch in the market, with clinical effectiveness as the main reason. CONCLUSION: There were many kinds of reasons for the disapproval registration applications of new traditional Chinese medicines in recent years in China, mainly including such problems as effectiveness, safety and proposal basis. This reflects problems occurring in R&D and registration administration of new traditional Chinese medicines in China to some extent.


Assuntos
Aprovação de Drogas/legislação & jurisprudência , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/normas , Animais , China , Ensaios Clínicos como Assunto , Aprovação de Drogas/organização & administração , Tratamento Farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/normas , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Fitoterapia
15.
Biologicals ; 39(5): 325-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21873077

RESUMO

With the expiration of patents on the first generation of rDNA biopharmaceuticals, competitors began to introduce biosimilar products. The concept of generics as applied to classical chemical drugs cannot be used for biotechnology products. Physicochemical characterization, bioassays and animal studies do not have the ability to predict reliably the safety and efficacy of biotherapeutics. Clinical studies are always necessary. While regulators all over the world were really in need of a comprehensive guideline in this area, WHO introduced a guideline which is principally a basis for regulating biosimilars and is applicable in Iran, as well as many other countries.


Assuntos
Aprovação de Drogas/legislação & jurisprudência , Avaliação de Medicamentos/legislação & jurisprudência , Avaliação de Medicamentos/normas , Indústria Farmacêutica/legislação & jurisprudência , Indústria Farmacêutica/normas , Preparações Farmacêuticas/normas , Animais , Aprovação de Drogas/organização & administração , Avaliação Pré-Clínica de Medicamentos/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Guias como Assunto , Humanos , Irã (Geográfico) , Organização Mundial da Saúde
16.
Am Heart J ; 157(5): 827-36, 836.e1, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19376308

RESUMO

Assessing the potential for a new drug to cause life-threatening arrhythmias is now an integral component of premarketing safety assessment. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline (ICH) E14 recommends the "Thorough QT Study" (TQT) to assess clinical QT risk. Such a study calls for careful evaluation of drug effects on the electrocardiographic QT interval at multiples of therapeutic exposure and with a positive control to confirm assay sensitivity. Yet for some drugs and diseases, elements of the TQT Study may be impractical or unethical. In these instances, alternative approaches to QT risk assessment must be considered. This article presents points to consider for evaluation of QT risk when alternative approaches are needed.


Assuntos
Drogas em Investigação/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Animais , Ensaios Clínicos Controlados como Assunto/métodos , Aprovação de Drogas/organização & administração , Avaliação Pré-Clínica de Medicamentos/métodos , Eletrocardiografia/efeitos dos fármacos , Humanos , Cooperação Internacional , Síndrome do QT Longo/fisiopatologia
18.
Am J Ther ; 15(5): 495-503, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18806527

RESUMO

Benefit and risk assessments are not only important to regulatory authorities but also important to the providers, patients, pharmaceutical industry, and payers. In order for patients and providers to continue to have access to new innovative medicines, which have some level of inherent risk, it is critical to have a systematic and balanced focus on understanding the safety risks and benefits to the patient during drug development, at the time of approval and postmarketing. There has been a significant amount of activity around efforts to improve the ability to assess risks in the postmarketing environment. However, there is no widely accepted, systematic approach or process for the ongoing evaluation of benefit. This article introduces 4 critical components in the process of identifying and assessing benefit with a goal of providing a framework that is transparent, comprehensive, applicable to various perspectives, and simple to communicate and implement. We propose the development of a catalog applied to a particular disease to identify the optimal data sources and methods to address the interests of a given perspective. Two key resources will need to be developed to support the catalog development: (1) a summary of benefit measures and preferences by disease and from various perspectives and (2) an investment in a simple visual communication mechanism with minimal statistical language. As the emphasis is on transparency, relevance, applicability, and communication, this approach to assessing benefit should maximize the impact of these data to all stakeholders and decision makers.


Assuntos
Aprovação de Drogas/estatística & dados numéricos , Indústria Farmacêutica/estatística & dados numéricos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Comunicação , Coleta de Dados/métodos , Aprovação de Drogas/organização & administração , Avaliação Pré-Clínica de Medicamentos/estatística & dados numéricos , Humanos , Vigilância de Produtos Comercializados/estatística & dados numéricos , Medição de Risco , Estados Unidos , United States Food and Drug Administration
19.
J Psychosoc Nurs Ment Health Serv ; 46(3): 17-20, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18416270

RESUMO

The first article of this series on the drug development process described the historical evolution of the U.S. Food and Drug Administration (FDA), and last month's article reviewed the ethical foundations of clinical research. Before a new drug is marketed, a sequence of preclinical investigations and three phases of clinical studies are conducted. This drug development process involves the FDA, pharmaceutical companies (sponsors), clinical investigators, and institutional review boards. This article further describes this aspect of the drug development process.


Assuntos
Aprovação de Drogas/organização & administração , United States Food and Drug Administration , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Objetivos Organizacionais , Gestão da Segurança/organização & administração , Estados Unidos , United States Food and Drug Administration/organização & administração
20.
Annu Rev Med ; 58: 1-16, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17059362

RESUMO

Despite advancements in genetics, chemistry, and protein engineering, recent years have seen fewer approvals of new drugs, increases in development costs, and high-profile drug withdrawals. This article focuses on technologic methods for improving drug development efficiency. These technologies include high-content cell screening, expression profiling, mass spectroscopy, mouse models of disease, and a post-launch screening program that enables investigations of adverse drug effects. Implementation of these new technologies promises to improve performance in drug development and safety.


Assuntos
Tecnologia Biomédica/métodos , Ensaios Clínicos como Assunto , Aprovação de Drogas/organização & administração , Avaliação Pré-Clínica de Medicamentos , Animais , Modelos Animais de Doenças , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Espectrometria de Massas , Camundongos , Estados Unidos
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