Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Apr 2019
ReviewShort commentary on NDMA (N-nitrosodimethylamine) contamination of valsartan products.
A range of generic valsartan products have been found to be contaminated with nitrosamines (principally N-nitrosodimethylamine; NDMA). We present information and discuss various elements of this phenomenon including: actions taken by regulatory agencies, source of the nitrosamine impurities, range of possible risk assessments based mainly on ICH M7 criteria, epidemiological assessment and analytical aspects.
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Regul. Toxicol. Pharmacol. · Feb 2019
ReviewLegal aspects of zebrafish neuropharmacology and neurotoxicology research.
Despite the growing emphasis on translational neuropharmacology and drug discovery research, the legality underlying these fields are seldom considered. The zebrafish (Danio rerio) is an increasingly utilized model organism in neuropharmacology and neurotoxicology. ⋯ Here, we discuss a wide range of regulatory topics relevant to zebrafish research, such as the bioethics of experimentation (including studies of stress and pain), welfare protection laws, the recent advances in CNS drug discovery, and specific legal aspects of controlled substance research in this aquatic species. The conceptualization and understanding of the zebrafish welfare and its promise as a model in toxicology can also potentially shape environmental protection practices and inform policy making.
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Regul. Toxicol. Pharmacol. · Nov 2017
ReviewAssessing modified risk tobacco and nicotine products: Description of the scientific framework and assessment of a closed modular electronic cigarette.
Cigarette smoking causes many human diseases including cardiovascular disease, lung disease and cancer. Novel tobacco products with reduced yields of toxicants compared to cigarettes, such as tobacco-heating products, snus and electronic cigarettes, hold great potential for reducing the harms associated with tobacco use. In the UK several public health agencies have advocated a potential role for novel products in tobacco harm reduction. ⋯ The US FDA, has provided draft guidance outlining a framework to assess novel products as Modified Risk Tobacco Products (MRTP). Based on this, we now propose a framework comprising pre-clinical, clinical, and population studies to assess the risk profile of novel tobacco products. Additionally, the utility of this framework is assessed through the pre-clinical and part of the clinical comparison of a commercial e-cigarette (Vype ePen) with a scientific reference cigarette (3R4F) and the results of these studies suggest that ePen has the potential to be a reduced risk product.
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Regul. Toxicol. Pharmacol. · Nov 2016
ReviewEvaluation of the Tobacco Heating System 2.2. Part 1: Description of the system and the scientific assessment program.
This publication introduces a series of eight other publications describing the non-clinical assessment and initial clinical study of a candidate modified risk tobacco product (MRTP) - the Tobacco Heating System 2.2 (THS2.2). This paper presents background information on tobacco harm reduction, to complement the approaches aimed at increasing smoking cessation and reducing smoking initiation to reduce the morbidity and mortality caused by cigarette smoking. THS2.2 heats tobacco without combustion, and the resulting formation of harmful and potentially harmful constituents (HPHC) is greatly reduced compared with cigarette smoke. ⋯ Additional mechanistic endpoints, measured as part of in vivo studies, confirmed reduced impact on smoking-related disease networks. The clinical study confirmed the reduced exposure to HPHCs in smokers switching to THS2.2, and the associated transcriptomic study confirmed the utility of a gene expression signature, consisting of only 11 genes tested in the blood transcriptome of subjects enrolled in the clinical study, as a complementary measure of exposure response. The potential of THS2.2 as an MRTP is demonstrated by the assessment and additional publications cited in this series.
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Generally Recognized as Safe (GRAS) substances are exempt from premarket approval; however, the standard of "reasonable certainty of no harm" is the same. In 1997, the voluntary GRAS affirmation process was replaced with the voluntary U. S. ⋯ Only four raised questions about potential safety, of which three received a no questions letter upon providing more data. Of the 84 withdrawn notices, 22 received a no questions letter upon resubmission. In spite of criticisms, the FDA GRAS notice process is clearly defined, efficient, and cost-effective, and there have been no known public health issues following its implementation.