Drug Substance and Drug Product Impurities, Now what?

Kelce, William R.

doi:10.15406/mojt.2017.03.00043

Cited by 9 publications

(6 citation statements)

References 1 publication

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“…These types of contaminants are most likely to arise during the synthesis, purification, and storage of the substance. Organic volatile impurities are residual solvents that are produced during the synthesis of drug substances or in excipients used in the production of drug formulations. , We have successfully identified key organic impurities in our process (Scheme ). Impurity 3a could be expected as a product of aromatic o - and p -disubstitution.…”

Section: Resultsmentioning

confidence: 99%

A Scalable Synthesis of Roxadustat (FG-4592)

Píša¹,

Rádl²,

Čerňa³

et al. 2021

Org. Process Res. Dev.

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A scalable five-step protocol for synthesis of roxadustat, an orally administered hypoxia-inducible factor-propyl hydroxylase inhibitor (HIF-PHI), was developed with an emphasis placed on aspects of medicinal chemistry. The isoquinoline core of the molecule was prepared using a purposefully designed cyclocondensation in which both the cyclocondensation and demasking of the groups being condensed is promoted by a common acid agent in one step. Roxadustat was obtained pure in a very competitive overall yield across all reaction steps and in compliance with permissible residual Pd level in API.

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Section: Resultsmentioning

confidence: 99%

A Scalable Synthesis of Roxadustat (FG-4592)

Píša¹,

Rádl²,

Čerňa³

et al. 2021

Org. Process Res. Dev.

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“…Zalecenia dotyczące minimalizowania ryzyka płynącego z obecności zanieczyszczeń w nowych substancjach czynnych oraz produktach leczniczych zawarte są w wytycznych ICH. Szczególnie istotny jest punkt Q3 [30] (Q jako skrót od ang. quality, czyli jakość), dotyczący w części Q3A -nowych substancji leczniczych, Q3B -nowych produktów leczniczych, Q3C -rozpuszczalników oraz Q3Dzanieczyszczeń elementarnych [26].…”

Section: Zanieczyszczenia W Produktach Leczniczych -Definicje Regulac...unclassified

Counterfeit and Illegal Medicinal Products as an Example of Drugs That Do Not Meet the Basic Quaity Requirements

Kalicka,

Tarłowska

2023

Prosp. Pharm. Sc.

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Falsification or counterfeiting of medicinal products is a severe pharmaceutical crime. According to the World Health Organization, about 10% of medicinal products in developing countries are falsified. In the case of medicines sold over the Internet, the figure is as high as 50%, and this phenomenon's scale is increasing yearly. The illegally sourced preparations are not manufactured in accordance with Good Manufacturing Practice (GMP). Among the most frequently falsified medicinal products are preparations used for erectile dysfunction, weight loss aids, or anabolic-androgenic steroids. The presence of undeclared active ingredients and impurities, incorrect dosage due to different than declared contents, and the sourcing of over-the-counter medicines from unknown sources can lead to serious side effects that threaten patients' lives and health. In addition, inaccurate or incomplete descriptions of product formulation can additionally cause the risk of drug interactions, which can consequently lead to serious medical incidents. The purpose of this paper is to discuss the requirements for medicinal products and to present the problem of the quality of counterfeit and illegal medicinal products. This issue is discussed using phosphodiesterase type 5 inhibitors (applied to the treatment of erectile dysfunction) as an example. KEYWORDS: falsified medicinal products, quality of medicinal products, PDE-5 inhibitors

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“…Study of impurities in pharmaceuticals is one of the most highly regarded topics; it is essential, but time consuming and challenging. In terms of regulations and technology, we must keep pace with the times [18,19]. Comprehensively speaking, aims to develop an impurity study have two major directions as follows: regulatory requirements and scientific/technical demands ( Table 1).…”

Section: Aims To Conduct Impurity Studymentioning

confidence: 99%

“…mutagenic impurities must be controlled to levels less than the threshold of toxicological concern based on lifetime exposure shall be evaluated as a risk consideration [16][17][18]. Adequate qualification must include genotoxicity and repeat-dose toxicology studies of appropriate duration to support the proposed indication.…”

Section: Aims To Conduct Impurity Studymentioning

confidence: 99%

See 1 more Smart Citation

Determination of Impurities in Pharmaceuticals: Why and How?

Liu¹,

Chen²

2019

Quality Management and Quality Control - New Trends and Developments

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The presence of impurities, particularly the API-related impurities, i.e., degradation-related impurities (DRIs) and interaction-related impurities (IRIs), may affect the quality, safety, and efficacy of drug products. Since the regulatory requirements and management strategies are required to be established and complied, sources of impurities shall be carefully classified prior to take subsequent steps such as development of analytical methods and acceptance criteria. Current international regulatory requirements for the management of impurities in pharmaceuticals were reviewed. Procedures for the identification of DPIs in pharmaceuticals, i.e., ethyl cysteinate dimer, (R)-N-methyl-3-(2-bromophenoxy)-3-phenylpropanamine, sestamibi, etc., using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were studied. Scheme for the establishment of analytical methods and acceptance criteria of process-related impurities (PRIs) and DRIs in accordance with the requirements of International Council for Harmonization (ICH) and algorithm to perform the identification of DPIs by using LC-MS/MS has been proposed. Practice of kinetic study to distinguish PRIs and DRIs, determination of the potential core fragments coupled with a predicted list of relevant transformations for conducting MS/MS scans, applications of stable isotope distribution patterns or natural abundances, practice of mass balance, etc., have been well demonstrated to justify the reliabilities of identification results.

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Drug Substance and Drug Product Impurities, Now what?

Cited by 9 publications

References 1 publication

A Scalable Synthesis of Roxadustat (FG-4592)

A Scalable Synthesis of Roxadustat (FG-4592)

Counterfeit and Illegal Medicinal Products as an Example of Drugs That Do Not Meet the Basic Quaity Requirements

Determination of Impurities in Pharmaceuticals: Why and How?

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