ECVAM's Role in the Implementation of the Three Rs Concept in the Field of Biologicals

Hendriksen, Coenraad; Cußler, Klaus; Halder, Marlies

doi:10.1177/026119290203002s06

Cited by 4 publications

(3 citation statements)

References 5 publications

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“…Although these methods are officially accepted, they often fail to detect toxicity, given that the manifestation time period of this type of effect may be too long for proper observation. However, the validation of sensitive, alternative methods for the early identification of toxic effects is as important as the limitation of restriction on the use of animals in experiments, as this would also prevent the unnecessary exposure of human beings to products that present a nephrotoxic potential, in turn decreasing the cost of developing new medicines (Prieto 2000;Hendriksen et al, 2002;Vanparys, 2002).…”

Section: Introductionmentioning

confidence: 99%

A comparison of BGM and LLC-PK1 cells for the evaluation of nephrotoxicity

Tagliati¹,

Romero²,

Dutra³

et al. 2011

Drug and Chemical Toxicology

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Nephrotoxicity is one of the most frequent effects observed after the use of medicine. Such situations have been tardily discovered because of existing methods to determine toxicity. The validation of sensitive, alternative methods for the early identification of toxic effects is as important as restrictions on the use of animals. In this light, the present study evaluated the effects of gentamicin on BGM and LLC-PK1 cells, using MTT and Neutral Red (NR). Although the LLC-PK1 cell line is used for toxicological studies, the BGM cell line is relatively new for this purpose. MTT (BGM: EC(50) = 6.29 mM; LLC-PK1: EC(50) = 8.01 mM) was found to be more sensitive than NR (EC(50) was greater than 10 mM for both cells). By using MTT, both cells demonstrated the involvement of mitochondria in a manner that was dose dependent, with an apoptotic process occurring at the concentrations of 1 and 3 mM and necrosis at concentrations above 4 mM. It could, therefore, be concluded that 1) BGM appears to be useful in the study of the mechanism of nephrotoxicity caused by gentamicin and 2) because of its sensitivity to MTT, in addition to its ease of manipulation, it is believed that the BGM cell line can also be used as an alternative method to evaluate nephrotoxicity.

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Section: Introductionmentioning

confidence: 99%

A comparison of BGM and LLC-PK1 cells for the evaluation of nephrotoxicity

Tagliati¹,

Romero²,

Dutra³

et al. 2011

Drug and Chemical Toxicology

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“…Vaccines' biological origin confers complexity and heterogeneity that, by definition, means that batches of the same product can vary qualitatively over time or between manufacturers [ 12 , 13 ]. Qualitative parameters—specified for U.S. veterinary markets within regulatory guidance as safety, purity, potency and efficacy as defined in standard requirements—are measured for each batch in order to determine the acceptability of the final product [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Batch potency testing regulations that aim to control this particular quality parameter have changed little since their introduction for many currently licensed vaccine products and continue to rely on the extensive use of live animals and challenge tests [ 12 , 16 , 17 ]. Potency regulations specify tests or types of tests that are considered acceptable for use by manufacturers in order to satisfy production standards for this aspect of vaccine quality.…”

Section: Introductionmentioning

confidence: 99%

Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods

Dozier¹,

Brown²,

Currie³

2011

Animals

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Simple SummaryMany vaccines are tested for quality in experiments that require the use of large numbers of animals in procedures that often cause significant pain and distress. Newer technologies have fostered the development of vaccine quality control tests that reduce or eliminate the use of animals, but the availability of these newer methods has not guaranteed their acceptance by regulators or use by manufacturers. We discuss a strategic approach that has been used to assess and ultimately increase the use of non-animal vaccine quality tests in the U.S. and U.K.AbstractIn recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.

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Assessment of recombinant human erythropoietin by alternative bioassay and its correlation with liquid chromatography methods

et al. 2013

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Biotechnology-derived erythropoietin is a sialoglycoprotein, which stimulates erythropoiesis, and it is clinically used for the treatment of anaemia related to chronic renal failure. N-Acetylneuraminic acid content was quantified by a reversed-phase liquid chromatography method with fluorescence detection giving values higher than 108.74 ng mg À1 . An alternative in vitro TF-1 cell proliferation bioassay was studied showing a lower mean difference of the estimated potency of 2.67%, compared to the normocythaemic mice bioassay, with non-significant differences (p > 0.05). Biopharmaceutical products were also analyzed by validated reversed-phase and size-exclusion liquid chromatography methods and compared to the in vivo bioassay, showing lower mean differences of the content/potencies of 2.11 and 1.21%, respectively. Higher molecular mass forms and deamidated/sulphoxide forms showed mean bioactivities reduced to about 10%, for both. The TF-1 cell culture assay in conjunction with the determination of sialic acids represents an advance that can be correlated with the normocythaemic mice bioassay and the physicochemical methods, allowing for the establishment of alternative methods, which can be applied to monitor the stability, quality control, and thereby ensuring the therapeutic efficacy of the biological medicine.

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ECVAM's Role in the Implementation of the Three Rs Concept in the Field of Biologicals

Cited by 4 publications

References 5 publications

A comparison of BGM and LLC-PK1 cells for the evaluation of nephrotoxicity

A comparison of BGM and LLC-PK1 cells for the evaluation of nephrotoxicity

Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods

Assessment of recombinant human erythropoietin by alternative bioassay and its correlation with liquid chromatography methods

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