Regulating impurities in pharmaceutical products: a tolerability of risk approach?

Bouder, Frédéric

doi:10.1586/17512433.1.2.241

Cited by 28 publications

(10 citation statements)

References 27 publications

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“…Good examples are genotoxic impurities (GTIs) that can easily contaminate final products. Such impurities are initiators of genetic mutation, chromosomal breaks or rearrangements, as well as cancers in humans, and therefore have to be avoided in the final products [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Removal of benzaldehyde from a water/ethanol mixture by applying scavenging techniques

Mitić

Skov²,

Gernaey

2016

Green Processing and Synthesis

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A presence of carbonyl compounds is very common in the food industry. The nature of such compounds is to be reactive and thus many products involve aldehydes/ketones in their synthetic routes. By contrast, the high reactivity of carbonyl compounds could also lead to formation of undesired compounds, such as genotoxic impurities. It can therefore be important to remove carbonyl compounds by implementing suitable removal techniques, with the aim of protecting final product quality. This work is focused on benzaldehyde as a model component, studying its removal from a water/ethanol mixture by applying different derivatization agents as the scavengers. Discovery chemistry is performed in the beginning as a screening procedure, followed by the process design of a small-scale continuous process for benzaldehyde removal with in-line real-time monitoring. Applications of tris(hydroxymethyl)aminomethane (TRIS) are found to provide above average removal of benzaldehyde.

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Section: Introductionmentioning

confidence: 99%

Removal of benzaldehyde from a water/ethanol mixture by applying scavenging techniques

Mitić

Skov²,

Gernaey

2016

Green Processing and Synthesis

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“…From the toxicological point of view, genotoxic impurities (GTIs) are the most dangerous contaminants for human health. Exposure to even low levels of such impurities present in the final active pharmaceutical ingredient (API) may induce genetic mutations and may potentially cause cancer in humans [9,10]. However, regardless of the solvent class, it is important to explore the possible opportunities to reduce or avoid the use of harmful solvents in the manufacturing process of pharmaceuticals.The use of ionic liquids (ILs) as nonconventional media in chemical synthesis is increasing attention because of their physical and chemical properties.…”

Section: Ionic Liquids In Pharmaceutical Industrymentioning

confidence: 99%

Ionic Liquids: Evident Application in Medicinal Chemistry

Sekar¹,

Kotramangalamb²,

Allurua³

et al. 2014

JCP

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In the present century an ever growing number of papers have been published describing the use of ionic liquids on organic synthesis. In general these works have shown evident advantages of this couple respect to conventional synthetic procedures for generation fast, efficient and environmental friendly synthetic methodologies. The industrial synthesis of pharmaceutical compounds often involves the use of organic solvents. Unfortunately, these reaction media are responsible for organic contaminations in the final product. In recent years, ionic liquids (ILs) have become the "green alternatives" of volatile organic solvents. Thus, the applications of ILs i nstead of con ve nti onal re a gents offer a new opportunity to solve problems of environmentally harmful solvents. This mini-review discusses a new application of ILs in laboratoryscale Pharmaceutical synthesis.

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“…The safety of a drug product is dependent not only on the toxicological properties of the active drug substance itself, but on the impurities it contains. Organic impurities that have the potential to induce genetic mutations, chromosomal breaks, and/or chromosomal rearrangements are considered as potential genotoxic impurities (PGIs), which may cause cancer in humans . Therefore, there is an ever‐increasing interest in controlling and monitoring of PGIs in APIs .…”

Section: Introductionmentioning

confidence: 99%

Identification, control strategies, and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals: A comprehensive review

Reddy

Jaafar

Umar

et al. 2015

J of Separation Science

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Potential genotoxic impurities in pharmaceuticals at trace levels are of increasing concern to both pharmaceutical industries and regulatory agencies due to their possibility for human carcinogenesis. Molecular functional groups that render starting materials and synthetic intermediates as reactive building blocks for small molecules may also be responsible for their genotoxicity. Determination of these genotoxic impurities at trace levels requires highly sensitive and selective analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical research and development. Experimental guidance for the analytical determination of some important classes of genotoxic impurities is still unavailable in the literature. Therefore, the present review explores the structural alerts of commonly encountered potential genotoxic impurities, draft guidance of various regulatory authorities in order to control the level of impurities in drug substances and to assess their toxicity. This review also describes the analytical considerations for the determination of potential genotoxic impurities at trace levels and finally few case studies are also discussed for the determination of some important classes of potential genotoxic impurities. It is the authors' intention to provide a complete strategy that helps analytical scientists for the analysis of such potential genotoxic impurities in pharmaceuticals.

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Regulating impurities in pharmaceutical products: a tolerability of risk approach?

Cited by 28 publications

References 27 publications

Removal of benzaldehyde from a water/ethanol mixture by applying scavenging techniques

Removal of benzaldehyde from a water/ethanol mixture by applying scavenging techniques

Ionic Liquids: Evident Application in Medicinal Chemistry

Identification, control strategies, and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals: A comprehensive review

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