The regulatory framework for preventing cross-contamination of pharmaceutical products: History and considerations for the future

Sargent, Edward V.; Flueckiger, Andreas; Barle, Ester Lovšin; Luo, Wendy; Molnar, Lance R.; Sandhu, Reena; Weideman, Patricia A.

doi:10.1016/j.yrtph.2016.05.029

Cited by 26 publications

(10 citation statements)

References 12 publications

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“…6 Similarly, pharmaceutical companies are actively improving cleaning and validation practices to avoid cross-contamination. 5,7 Many studies use analytical equipment to determine the concentration of leftover active pharmaceutical ingredient (API) components 8,9 as well as the acceptable carryover of compounds to the next batch in cleaning validation protocols. 5,10,11 However, wide screening for cross-contaminants is difficult since detection depends on the chemical compounds of interest.…”

Section: ■ Introductionmentioning

confidence: 99%

“…There were also repeated incidents that the U.S. Food and Drug Administration (FDA) attributed to the failure to adequately clean and sterilize equipment. , Crucially, insufficient cleaning was among the top 10 reasons that pharmaceutical plants failed FDA inspections. To assuage public concerns about the safety of pharmaceutical products, since 1978, global health authorities have regularly updated guidance and regulations that require pharmaceutical manufacturing plants to scientifically verify the removal of compounds in the cleaning process. Furthermore, the rationale for product usage in cleaning validation and verification operations is necessary .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the rationale for product usage in cleaning validation and verification operations is necessary . Similarly, pharmaceutical companies are actively improving cleaning and validation practices to avoid cross-contamination. , …”

Section: Introductionmentioning

confidence: 99%

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Understanding the Adsorption and Desorption of Sitagliptin Phosphate Monohydrate on SS2343, Glass, and PTFE Using QCM-D and Raman Spectroscopy

et al. 2022

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Cross-contamination during pharmaceutical drug manufacturing can result in expensive recalls. To counter that, companies spend significant time and resources to ensure equipment cleanliness, often relying on the compound solubility data in various solvents as the main indicator of cleaning success. The aim of this work is to provide an alternative way to analyze the fouling and cleaning of surfaces in pharmaceutical manufacturing processes by using the quartz crystal microbalance with dissipation (QCM-D) and Raman spectroscopy. In this study, we chose an active pharmaceutical ingredient (API), sitagliptin phosphate monohydrate (SIT), as the model drug compound and observed its adsorption and desorption on stainless steel (SS2343), borosilicate glass (glass), and polytetrafluoroethylene (PTFE) surfaces. SIT was selected as the model API since it is a product manufactured on a large scale and is part of the widely used dipeptidyl peptidase-IV inhibitor class of oral hypoglycemics used to treat type 2 diabetes mellitus, while the chosen surfaces mimic the wall materials of manufacturing equipment and components such as reactors, transfer lines, and valves. Both the QCM-D and Raman spectroscopy results show the highest physisorption on PTFE, followed by SS2343 and glass. Additionally, QCM-D revealed a harder removal of SIT from SS2343 compared to glass and PTFE. Raman analysis of the chemical interactions disclosed C−F and C�O bond interactions between SIT and the surfaces, and the lack of a peak shift suggested dipole−dipole interactions. Furthermore, contact angle measurements indicate that hydrophobic attraction contributed to SIT adhesion to the PTFE surface. Subsequently, SIT coverage upon deposition on a PTFE surface has a significantly smaller surface area than on SS2343 and glass due to surface hydrophobicity, hence resulting in a longer removal time. These results provide a practical use of QCM-D and Raman spectroscopy to enhance the understanding of fouling and improve the cleaning of complex small molecules on relevant surfaces during the pharmaceutical manufacturing process.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Understanding the Adsorption and Desorption of Sitagliptin Phosphate Monohydrate on SS2343, Glass, and PTFE Using QCM-D and Raman Spectroscopy

et al. 2022

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“…Additionally, the residual solvent present in the final product is an environmental and health concern. Due to its toxicity, regulatory agencies worldwide may require control and elimination of this residue especially in drugs . Therefore, the development of environmentally friendly solvent-free reactions continues to be of great interest.…”

Section: Introductionmentioning

confidence: 99%

“…Due to its toxicity, regulatory agencies worldwide may require control and elimination of this residue especially in drugs. 7 Therefore, the development of environmentally friendly solvent-free reactions continues to be of great interest. The hydrogenation of α and/or β-pinene is an interesting model to investigate because it is a greener reaction to obtain pinanes exempt from solvent traces compared to hydrogenation performed in ethyl acetate as an example.…”

Section: ■ Introductionmentioning

confidence: 99%

Green Hydrogenation: Solvent-Free Hydrogenation of Pinenes for An Undergraduate Organic Chemistry Laboratory

et al. 2020

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Reorienting organic chemistry laboratories with an emphasis on systemic thinking can only be beneficial to students. Addressing the challenges of climate change and the development of renewable resources with a fundamental reaction, such as the hydrogenation of an alkene, will allow students to see organic chemistry as a science beneficial to society. For this purpose, a green organic laboratory experiment in which students performed solvent-free catalytic hydrogenation of β- or α-pinene was developed. Using a homemade high- or low-pressure autoclave, solvent-free hydrogenation of β- or α-pinene over Pd/C produced a mixture of cis- and trans-pinanes. The monitoring of the reaction by NMR, IR, and GC-MS allowed the students to be familiar with the isomerization of an alkene and the shift of an equilibrium according to Le Chatelier’s principle. The filtration of the catalyst near the halftime of reaction and the continuation of the hydrogenation off catalyst allowed the students to confirm the heterogeneous nature of the hydrogenation.

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Noncancer Risk Assessment: Principles and Practice in Environmental and Occupational Settings

Pecquet,

Haber

2023

Patty's Toxicology

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The scientific process of risk assessment aims to define hazards associated with human exposure to chemicals. This chapter focuses primarily on the first two steps of the risk assessment process for noncancer endpoints, or more broadly, for modes of action not involving interaction with DNA. Hazard characterization consists of a systematic evaluation of available data to identify toxicologically relevant adverse outcomes, the associated mode of action, and evaluation of human relevance of the effects. Data quality and the overall weight of evidence are also evaluated. We summarize available technologies for dose–response assessment to define the critical effect and to extrapolate effect levels to human exposure scenarios and exposure durations, and we discuss methods for addressing uncertainties. Methods for evaluating data–poor chemicals or conducting screening assessments are also reviewed. Finally, we discuss how to interpret the dose–response information in the context of specific exposure data. Although this chapter focuses on the methods for deriving risk values from in vivo studies, we also address the use of data from the rapidly evolving field of new approach methodologies (including in vitro methods such as high‐throughput transcriptomics and in silico approaches such as modeling of structure–activity relationships). Ultimately, these new methodologies will foster a better understanding of how chemical exposures may cause toxicity, allow for more rapid assessment of chemicals, and support a reduction in the need for future toxicity testing in animals.

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The regulatory framework for preventing cross-contamination of pharmaceutical products: History and considerations for the future

Cited by 26 publications

References 12 publications

Understanding the Adsorption and Desorption of Sitagliptin Phosphate Monohydrate on SS2343, Glass, and PTFE Using QCM-D and Raman Spectroscopy

Understanding the Adsorption and Desorption of Sitagliptin Phosphate Monohydrate on SS2343, Glass, and PTFE Using QCM-D and Raman Spectroscopy

Green Hydrogenation: Solvent-Free Hydrogenation of Pinenes for An Undergraduate Organic Chemistry Laboratory

Noncancer Risk Assessment: Principles and Practice in Environmental and Occupational Settings

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