Special endpoint and product specific considerations in pharmaceutical acceptable daily exposure derivation

Gould, Janet C.; Callis, Courtney M.; Dolan, David G.; Stanard, Brad; Weideman, Patricia A.

doi:10.1016/j.yrtph.2016.05.022

Cited by 23 publications

(5 citation statements)

References 117 publications

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“…Unlike donkey skin-made CCA, the efficacy and safety of which have been tested in human trials for over 2,000 years, the gelatin made from other animal species may cause severe problems. 7 On the one hand, it could possess little to no effect compared to the authentic products. On the other hand, infectious risks are associated with some animal species.…”

Section: Introductionmentioning

confidence: 99%

Species-specific identification of collagen components in Colla corii asini using a nano-liquid chromatography tandem mass spectrometry proteomics approach

Li¹,

Shi²,

Gong³

et al. 2017

IJN

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Colla corii asini (CCA) is a protein-based traditional Chinese medicine made from donkey skins. Because it has the ability to nourish blood, its demand is increasing rapidly. The shortage of donkey skins increases the risk of the adulteration of CCA products with other animal skins. To ensure the drug efficacy and safety of CCA products, a proteomics technique was applied to reveal proteins in the skins of donkey, horse, cattle, and pig. Species-specific peptides for each animal species were predicted using bioinformatics, and their presence in the skins and gelatin samples was examined by nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS). One unique marker peptide for each animal species was selected to develop an LC-MS/MS multiple reaction monitoring method. The capability of this method to identify donkey, horse, cattle, and pig materials was demonstrated by analyzing in-house-made donkey gelatins containing different amounts of other animal skins and commercial CCA products. The adulteration of non-donkey species could be sensitively detected at a low level of 0.5%. Hybrid animals, such as mules and hinnies, were also differentiated from donkeys. We provide a practical tool for the quality control of CCA products. The strategy can also be used to study other important traditional Chinese medicines which contain animal proteins.

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Section: Introductionmentioning

confidence: 99%

Species-specific identification of collagen components in Colla corii asini using a nano-liquid chromatography tandem mass spectrometry proteomics approach

Li¹,

Shi²,

Gong³

et al. 2017

IJN

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“…For illustrative purposes, Table 1 presents a typical pharmaceutical compound banding system and is the one employed by Bristol Myers Squibb (BMS). The cutoffs for the bands/categories presented are based on several factors, including approaches based on the threshold of toxicological concern (TTC) ( NIOSH, 2019 ; Dolan et al, 2005 ; Kroes et al, 2004 ; Cramer et al, 1978 ; Gould et al, 2016 ; Guideline, 2018 ). While the TTC may not be originally derived for occupational purposes, the principles have been applied successfully in the field of occupational health and safety for the establishment of safe occupational exposure limits ( Chebekoue and Krishnan, 2017 , 2019 ; Carthew et al, 2009 ; Hoersch et al, 2018 ).…”

Section: Occupational Exposure Control Bandingmentioning

confidence: 99%

Considerations for setting occupational exposure limits for novel pharmaceutical modalities

Graham

Hillegass

Schulze

2020

Regulatory Toxicology and Pharmacology

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In order to develop new and effective medicines, pharmaceutical companies must be modality agnostic. As science reveals an enhanced understanding of biological processes, new therapeutic modalities are becoming important in developing breakthrough therapies to treat both rare and common diseases. As these new modalities progress, concern and uncertainty arise regarding their safe handling by the researchers developing them, employees manufacturing them and nurses administering them. This manuscript reviews the available literature for emerging modalities (including oligonucleotides, monoclonal antibodies, fusion proteins and bispecific antibodies, antibody-drug conjugates, peptides, vaccines, genetically modified organisms, and several others) and provides considerations for occupational health and safety-oriented hazard identification and risk assessments to enable timely, consistent and well-informed hazard identification, hazard communication and risk-management decisions. This manuscript also points out instances where historical exposure control banding systems may not be applicable (e.g. oncolytic viruses, biologics) and where other occupational exposure limit systems are more applicable (e.g. Biosafety Levels, Biologic Control Categories).

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“…Genotoxicity is an endpoint which needs additional expert consideration with respect to the underlying mechanism of genotoxic effects since they may or may not be a part of the intended effects of the drugs. The term "genotoxic" has been used broadly to describe toxicological endpoints such as mutagenicity, structural chromosomal damage (clastogenic activity), and numerical chromosome aberrations (aneugenic activity), as well as end points not routinely used such as sister chromatid exchanges or unscheduled DNA synthesis (Gould et al, 2016). Within this context, the term mutagenicity more specifically describes DNA-reactive substances that have a potential to directly cause DNA damage, often even when present at low levels, leading to damage and therefore potentially initiating cancer (eg, alkylating agents or some DNA intercalators).…”

Section: Interpretation Of Genotoxic Dose-response Effects For Dsmentioning

confidence: 99%

Setting Occupational Exposure Limits for Genotoxic Substances in the Pharmaceutical Industry

et al. 2016

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In the pharmaceutical industry, genotoxic drug substances are developed for life-threatening indications such as cancer. Healthy employees handle these substances during research, development, and manufacturing; therefore, safe handling of genotoxic substances is essential. When an adequate preclinical dataset is available, a risk-based decision related to exposure controls for manufacturing is made following a determination of safe health-based limits, such as an occupational exposure limit (OEL). OELs are calculated for substances based on a threshold dose-response once a threshold is identified. In this review, we present examples of genotoxic mechanisms where thresholds can be demonstrated and OELs can be calculated, including a holistic toxicity assessment. We also propose a novel approach for inhalation Threshold of Toxicological Concern (TTC) limit for genotoxic substances in cases where the database is not adequate to determine a threshold.

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Special endpoint and product specific considerations in pharmaceutical acceptable daily exposure derivation

Cited by 23 publications

References 117 publications

Species-specific identification of collagen components in Colla corii asini using a nano-liquid chromatography tandem mass spectrometry proteomics approach

Species-specific identification of collagen components in Colla corii asini using a nano-liquid chromatography tandem mass spectrometry proteomics approach

Considerations for setting occupational exposure limits for novel pharmaceutical modalities

Setting Occupational Exposure Limits for Genotoxic Substances in the Pharmaceutical Industry

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