A SPS Survey on Cardiovascular Safety Pharmacology Practices Assessing Proarrhythmia Risk in Drug Safety Testing: State of the Art Prior to Implementation of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) Paradigm

2017 ◽  
Vol 88 ◽  
pp. 245
Author(s):  
Michael K. Pugsley ◽  
Bernard Fermini ◽  
John Koerner ◽  
Krystle Correll ◽  
Simon Authier ◽  
...  
Keyword(s):  
Drug Safety ◽  
State Of The Art ◽  
Cardiovascular Safety ◽  
Safety Testing ◽  
Safety Pharmacology

Establishing in vitro to clinical correlations in the evaluation of cardiovascular safety pharmacology

2013 ◽  
Vol 10 (3) ◽  
pp. e373-e383 ◽  
Author(s):  
A.S.Y. Chain ◽  
M.C.J.M. Sturkenboom ◽  
M. Danhof ◽  
O.E. Della Pasqua
Keyword(s):  
Cardiovascular Safety ◽  
Safety Pharmacology ◽  
Clinical Correlations

The ECVAM Workshops: A Critical Assessment of their Impact on the Development, Validation and Acceptance of Alternative Methods

2002 ◽  
Vol 30 (2_suppl) ◽  
pp. 151-165 ◽  
Author(s):  
Robert D. Combes
Keyword(s):  
State Of The Art ◽  
Substantial Effect ◽  
Alternative Methods ◽  
Current Status ◽  
In Vitro Tests ◽  
Regulatory Requirements ◽  
Safety Testing ◽  
Task Forces ◽  
Development And Validation

ECVAM initiated its workshop programme in 1994, to enable it to become well informed about the state of the art of non-animal test development and validation, and about the possible incorporation of alternatives into regulatory requirements for safety testing. Fifty-one such workshops had been held on specific topics, up to 2002. In these workshops, the current status of in vitro tests and their potential uses were reviewed and recommendations were made as to the best ways forward to progress and enhance the use of in vitro methods. Reports for 46 of these workshops have been published in ATLA. Most of the workshops focused on in vitro replacement methods, although an increasing number have dealt with reduction and refinement. The recommendations in the ECVAM workshops have been progressed further by: a) the formation of ECVAM task forces; b) the organisation of further workshops; c) the activities of scientific committees; d) the provision of earmarked research funding; and e) the conduct of validation studies. Examples of each of these activities are discussed. Some individual workshops are covered in more detail, and several recommendations that have so far not been acted on are also considered. The workshops and their reports have had a substantial effect on the development and implementation of alternative methods, and have been a major factor in contributing to the success of the first nine years of ECVAM's existence. It is strongly recommended that ECVAM continues to organise workshops and to publish their findings, and suggestions are made for topics for future workshops.

scholarly journals Development and use of in vitro alternatives to animal testing by the pharmaceutical industry 1980–2013

2015 ◽  
Vol 4 (5) ◽  
pp. 1297-1307 ◽  
Author(s):  
Jen-Yin Goh ◽  
Richard J. Weaver ◽  
Libby Dixon ◽  
Nicola J. Platt ◽  
Ruth A. Roberts
Keyword(s):  
Pharmaceutical Industry ◽  
Animal Testing ◽  
Genetic Toxicology ◽  
Safety Testing ◽  
Safety Pharmacology ◽  
Alternatives To Animal Testing ◽  
Ich Guidelines ◽  
Preclinical Safety

An analysis of the use ofin vitrotechniques in preclinical safety testing revealed a marked increase to >180 000 tests/year by 2012. Step changes in uptake were notable in the three main areas of ADME, safety pharmacology and genetic toxicology, correlated with relevant ICH guidelines.

scholarly journals State-of-the-art methods and devices for generation, exposure, and collection of aerosols from e-vapor products

2020 ◽  
Vol 4 ◽  
pp. 239784732097975
Author(s):  
Stéphanie Boué ◽  
Didier Goedertier ◽  
Julia Hoeng ◽  
Anita Iskandar ◽  
Arkadiusz K Kuczaj ◽  
...  
Keyword(s):  
Ad Hoc ◽  
State Of The Art ◽  
Physicochemical Characterization ◽  
Objective Evaluation ◽  
Vapor Generation ◽  
Characterization Methods ◽  
Clinical Exposure ◽  
Aerosol Generation

E-vapor products (EVP) have become popular alternatives for cigarette smokers who would otherwise continue to smoke. EVP research is challenging and complex, mostly because of the numerous and rapidly evolving technologies and designs as well as the multiplicity of e-liquid flavors and solvents available on the market. There is an urgent need to standardize all stages of EVP assessment, from the production of a reference product to e-vapor generation methods and from physicochemical characterization methods to nonclinical and clinical exposure studies. The objective of this review is to provide a detailed description of selected experimental setups and methods for EVP aerosol generation and collection and exposure systems for their in vitro and in vivo assessment. The focus is on the specificities of the product that constitute challenges and require development of ad hoc assessment frameworks, equipment, and methods. In so doing, this review aims to support further studies, objective evaluation, comparison, and verification of existing evidence, and, ultimately, formulation of standardized methods for testing EVPs.

scholarly journals Improving drug safety predictions by reducing poor analytical practices

2020 ◽  
Vol 4 ◽  
pp. 239784732097863
Author(s):  
Stanley E Lazic ◽  
Dominic P Williams
Keyword(s):  
At Risk ◽  
Drug Discovery ◽  
Drug Safety ◽  
Prediction Models ◽  
Predictive Modelling ◽  
Equal Weight ◽  
Negative Consequences ◽  
Preclinical Data ◽  
Safety Pharmacology ◽  
Patients At Risk

Predicting the safety of a drug from preclinical data is a major challenge in drug discovery, and progressing an unsafe compound into the clinic puts patients at risk and wastes resources. In drug safety pharmacology and related fields, methods and analytical decisions known to provide poor predictions are common and include creating arbitrary thresholds, binning continuous values, giving all assays equal weight, and multiple reuse of information. In addition, the metrics used to evaluate models often omit important criteria and models’ performance on new data are often not assessed rigorously. Prediction models with these problems are unlikely to perform well, and published models suffer from many of these issues. We describe these problems in detail, demonstrate their negative consequences, and propose simple solutions that are standard in other disciplines where predictive modelling is used.

scholarly journals Fabry Disease Therapy: State-of-the-Art and Current Challenges

2020 ◽  
Vol 22 (1) ◽  
pp. 206
Author(s):  
Olga Azevedo ◽  
Miguel Fernandes Gago ◽  
Gabriel Miltenberger-Miltenyi ◽  
Nuno Sousa ◽  
Damião Cunha
Keyword(s):  
Fabry Disease ◽  
State Of The Art ◽  
Large Body ◽  
Real Life ◽  
Clinical Manifestations ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
New Therapies ◽  
Enzyme Replacement

Fabry disease (FD) is a lysosomal storage disorder caused by mutations of the GLA gene that lead to a deficiency of the enzymatic activity of α-galactosidase A. Available therapies for FD include enzyme replacement therapy (ERT) (agalsidase alfa and agalsidase beta) and the chaperone migalastat. Despite the large body of literature published about ERT over the years, many issues remain unresolved, such as the optimal dose, the best timing to start therapy, and the clinical impact of anti-drug antibodies. Migalastat was recently approved for FD patients with amenable GLA mutations; however, recent studies have raised concerns that “in vitro” amenability may not always reflect “in vivo” amenability, and some findings on real-life studies have contrasted with the results of the pivotal clinical trials. Moreover, both FD specific therapies present limitations, and the attempt to correct the enzymatic deficiency, either by enzyme exogenous administration or enzyme stabilization with a chaperone, has not shown to be able to fully revert FD pathology and clinical manifestations. Therefore, several new therapies are under research, including new forms of ERT, substrate reduction therapy, mRNA therapy, and gene therapy. In this review, we provide an overview of the state-of-the-art on the currently approved and emerging new therapies for adult patients with FD.

scholarly journals State of the art on lung organoids in mammals

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Fabienne Archer ◽  
Alexandra Bobet-Erny ◽  
Maryline Gomes
Keyword(s):  
Lung Development ◽  
One Health ◽  
State Of The Art ◽  
Animal Health ◽  
In Vitro Models ◽  
Cancer Genetic ◽  
3 Dimensional ◽  
The One ◽  
Species Specific

AbstractThe number and severity of diseases affecting lung development and adult respiratory function have stimulated great interest in developing new in vitro models to study lung in different species. Recent breakthroughs in 3-dimensional (3D) organoid cultures have led to new physiological in vitro models that better mimic the lung than conventional 2D cultures. Lung organoids simulate multiple aspects of the real organ, making them promising and useful models for studying organ development, function and disease (infection, cancer, genetic disease). Due to their dynamics in culture, they can serve as a sustainable source of functional cells (biobanking) and be manipulated genetically. Given the differences between species regarding developmental kinetics, the maturation of the lung at birth, the distribution of the different cell populations along the respiratory tract and species barriers for infectious diseases, there is a need for species-specific lung models capable of mimicking mammal lungs as they are of great interest for animal health and production, following the One Health approach. This paper reviews the latest developments in the growing field of lung organoids.

Tocotrienols and Cancer: From the State of the Art to Promising Novel Patents

2019 ◽  
Vol 14 (1) ◽  
pp. 5-18 ◽  
Author(s):  
Fabrizio Fontana ◽  
Michela Raimondi ◽  
Monica Marzagalli ◽  
Roberta M. Moretti ◽  
Marina Montagnani Marelli ◽  
...  
Keyword(s):  
Cancer Prevention ◽  
State Of The Art ◽  
Synergistic Effects ◽  
The State ◽  
Therapeutic Interventions ◽  
Multiple Tumor ◽  
Anti Cancer ◽  
Important Health

Background: Tocotrienols (TTs) are vitamin E derivatives naturally occurring in several plants and vegetable oils. Like Tocopherols (TPs), they comprise four isoforms, α, β, γ and δ, but unlike TPs, they present an unsaturated isoprenoid chain. Recent studies indicate that TTs provide important health benefits, including neuroprotective, anti-inflammatory, anti-oxidant, cholesterol lowering and immunomodulatory effects. Moreover, they have been found to possess unique anti-cancer properties.Objective:The purpose of this review is to present an overview of the state of the art of TTs role in cancer prevention and treatment, as well as to describe recent patents proposing new methods for TTs isolation, chemical modification and use in cancer prevention and/or therapy.Methods:Recent literature and patents focusing on TTs anti-cancer applications have been identified and reviewed, with special regard to their scientific impact and novelty.Results:TTs have demonstrated significant anti-cancer activity in multiple tumor types, both in vitro and in vivo. Furthermore, they have shown synergistic effects when given in combination with standard anti-cancer agents or other anti-tumor natural compounds. Finally, new purification processes and transgenic sources have been designed in order to improve TTs production, and novel TTs formulations and synthetic derivatives have been developed to enhance their solubility and bioavailability.Conclusion:The promising anti-cancer effects shown by TTs in several preclinical studies may open new opportunities for therapeutic interventions in different tumors. Thus, clinical trials aimed at confirming TTs chemopreventive and tumor-suppressing activity, particularly in combination with standard therapies, are urgently needed.

Sign in / Sign up

Export Citation Format

Share Document