Safety and Efficacy: The Role of Chemistry, Manufacturing, and Controls in Pharmaceutical Drug Development

Difeo, Thomas J.

doi:10.1081/ddc-120030428

Cited by 3 publications

(3 citation statements)

References 35 publications

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“…Chemistry, Manufacturing, and Controls (CMC) is an integral part of any pharmaceutical product application to FDA. There is an intrinsic link between the CMC attributes of a pharmaceutical product and the safety and efficacy of clinical therapy ( 14 ). The US Pharmacopeia (USP) and the National Formulary (NF) drug substance and excipient monographs, as well as general tests and procedures, are frequently cited in New Drug Applications (NDA) ( 15 ), and a summary of pharmaceutical test scheme for pharmaceuticals and DSs is presented in Table 1 .…”

Section: Introductionmentioning

confidence: 99%

Chemical, Manufacturing, and Standardization Controls of Grape Polyphenol Dietary Supplements in Support of a Clinical Study: Mass Uniformity, Polyphenol Dosage, and Profiles

Lyu

Rodríguez²,

Ferruzzi

et al. 2021

Front. Nutr.

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Bioactive dietary polyphenols in grape (Vitis vinifera) have been used in Dietary Supplements (DSs) with the aim to prevent numerous diseases, including cardiovascular and neurodegenerative diseases, and to reduce depression and anxiety. Given prior recognition that DSs can be quality challenged from the purity, authentication, adulteration, and actual concentration of targeted bioactives, to ensure consumer health protection as well as the quality and safety of grape polyphenol-based DSs, the present investigation was aimed at establishing a comprehensive quality control (QC) approach for grape polyphenol-based DSs in support of a human clinical study. In this study, the manufactured grape seed polyphenol extract (GSPE) and trans-resveratrol (RSV) capsules and Concord Grape Juice (CGJ) along with the corresponding original drug materials were analyzed using the developed different liquid chromatography/UV-visible spectroscopy/mass spectrometry (LC/UV-Vis/MS) methods. The weight variation of GSPE and RSV capsules was also evaluated according to the US Pharmacopeia (USP) tests. The results indicate that the total identified polyphenol content in each grape seed extract (GSE) capsule/CGJ is very similar and all GSE/RSV capsules pass the content/weight uniformity test. Given the complexity of these and many botanical products from the issues of purity, quality, adulteration, consistency, and their coupling to the complex chemistry in each grape-derived botanical, quality assurance and the steps needed to ensure grape-derived DSs being well homogeneous and stable and containing the known and expected bioactives at specific concentration ranges are fundamental to any research study and in particular to a clinical trial. Each of these issues is essential to provide a solid foundation upon which clinical trials with botanicals can be conducted with the goal of realizing measurable mental health outcomes such as reducing depression and anxiety as well as understanding of their underlying biological mechanisms.

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Section: Introductionmentioning

confidence: 99%

Chemical, Manufacturing, and Standardization Controls of Grape Polyphenol Dietary Supplements in Support of a Clinical Study: Mass Uniformity, Polyphenol Dosage, and Profiles

Lyu

Rodríguez²,

Ferruzzi

et al. 2021

Front. Nutr.

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“…This way oxidation of Met resulted in the formation of Met-sulfoxide [67]. Moreover, impurities present in the excipients are found to be responsible for the enhanced oxidative degradation [66]. In lyophilized peptide formulations, sugars are the most commonly used excipients, but they are known to react with Gly and Arg via the Maillard reaction [91].…”

Section: Fdps (Drug Products)mentioning

confidence: 99%

“…Eur. include normal-phase HPLC, thin layer chromatography (TLC) and capillary zone electrophoresis (CZE), while other detection techniques may consist of NMR, fluorescence, refractive index and evaporative light scattering [66,67].…”

Section: Purity Of Peptidesmentioning

confidence: 99%

Purity profiling of Peptide Drugs

Verbeken¹

2012

JBABM

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The quality of a peptide drug mainly depends on its impurity profile, with the emphasis on the related impurities. These impurities may be biomedically active, alter the desired efficacy or induce unwanted toxicity, an aspect which is termed the "functional quality" of the peptide drug. Therefore, regulatory authorities have set up guidances or have legally established specification limits to assure a consistent purity of these peptide drugs. For the active pharmaceutical ingredients (APIs), the pharmacopoeial monographs are legally binding. Additional information can be found in regional and international guidelines. For the finished pharmaceutical drug products (FDPs) containing peptide active ingredients, only general guidelines are available. The construction of a complete related-impurity profile is very challenging due to the wide availability of different protecting groups, coupling agents and additives that may be used during peptide synthesis. In addition, chemical degradation, occurring during synthesis, formulation or at storage, may occur as well, including not only so-called pure chemical degradation but interaction with excipients as well. This review provides an update of the regulatory and scientific rationales behind the related impurities in peptide drugs.

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