Collaborative study for the validation of alternative in vitro potency assays for human tetanus immunoglobulins

Groß, Steffen W.; Janssen, Samuel; Vries, Bart de; Terao, E; Daas, A; Buchheit, Karl-Heinz

doi:10.1016/j.biologicals.2010.03.004

Cited by 4 publications

(9 citation statements)

References 2 publications

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“…However, a2AP-I treatment or a2AP deficiency significantly decreased microvascular thrombosis in comparison to control or to r-tPAtreated mice. 69 Consistent with this observation, plasminogen deficiency enhances, and high plasminogen levels reduce microvascular thrombosis in experimental ischemic stroke. 70 The extent of microvascular thrombosis was more strongly associated with the sequelae of severe ischemic brain injury than the magnitude of dissolution of the middle cerebral thrombus.…”

Section: Effects Of α 2 -Antiplasmin On the Ischemic Brain Microvascumentioning

confidence: 57%

α2-Antiplasmin: New Insights and Opportunities for Ischemic Stroke

Reed

Houng

Singh

et al. 2016

Semin Thromb Hemost

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Thrombotic vascular occlusion is the leading cause of ischemic stroke. High blood levels of α2-antiplasmin, an ultrafast, covalent inhibitor of plasmin, have been linked in humans to increased risk of ischemic stroke and failure of tissue plasminogen activator therapy. Consistent with these observations, α2-antiplasmin neutralizes the therapeutic benefit of tissue plasminogen activator therapy in experimental stroke. In addition, α2-antiplasmin has deleterious, dose-related effects on ischemic brain injury in the absence of therapy. Experimental therapeutic inactivation of α2-antiplasmin markedly reduces microvascular thrombosis, ischemic brain injury, brain swelling, brain hemorrhage and death after thromboembolic stroke. These data provide new insights into the critical importance of α2-antiplasmin in the pathogenesis of ischemic brain injury and suggest that transiently inactivating α2-antiplasmin may have therapeutic value in ischemic stroke.

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Section: Effects Of α 2 -Antiplasmin On the Ischemic Brain Microvascumentioning

confidence: 57%

α2-Antiplasmin: New Insights and Opportunities for Ischemic Stroke

Reed

Houng

Singh

et al. 2016

Semin Thromb Hemost

View full text Add to dashboard Cite

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“…Validation should be considered when developing or modifying validated methodologies. Several studies in the literature report on validating methods for potency determination [1][2][3][4][5][6][7][8][10][11][12][13]22,[35][36][37][38][41][42][43][44][45][46][47][48][49][50][51][52][53][54] , describing the approaches to designing validation, acceptance criteria, data analysis and interpretation, and even performance monitoring through quality control 9,38,55,56,57,58,59,60,61,62 . ICH Q2 (R1) is considered the primary reference for recommendations and definitions of validation characteristics of analytical procedures for pharmaceuticals for human use.…”

Section: Validation Proceduresmentioning

confidence: 99%

“…An enzymatic immunoassay (EIA) and a toxin inhibition assay (TIA) showed good reproducibility, precision, and repeatability in an international collaborative study. The methods discriminated between low, medium and high potency were, therefore, considered adequate for the quality control of human tetanus immunoglobulin 10 .…”

Section: Tetanus Immunoglobulinmentioning

confidence: 99%

“…The EIA and TIA were submitted to a complementary collaborative study to be validated in high potency products. The assays were able to recognize between low, medium and high potency samples using a precision concept that was understood as reliability since it determined the intra-(repeatability) and inter-(reproducibility) laboratory variations 10 .…”

Section: Tetanus Immunoglobulinmentioning

confidence: 99%

“…Several tests required by the regulatory agencies and guidelines for ensuring product efficacy and safety use too many animals causing them significant pain and suffering 1,2,3,4,5,6,7,8,9,10,11,12,13 . It has been estimated that about 10 million laboratory animals are used in the industry and quality control of biologicals worldwide yearly, of which 80% is required for testing safety and potency in batch release 14 .…”

Section: Introductionmentioning

confidence: 99%

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Alternative potency tests for quality control of immunobiologicals: a critical review of the validation approach

et al. 2020

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Introduction: In addition to low reproducibility, in vivo potency tests used in the quality control of immunobiological products require too many animals, causing them significant pain and suffering. In the last decades, many studies have been conducted to validate alternative methods for quality control and batch release of products such as vaccines and other immunobiologicals, especially for potency tests. Objective: To discuss validation studies on alternative methods proposed for replacing the in vivo potency tests and the used statistical approach, as well as to propose harmonization of terminology and to design validation studies for alternative potency methods. Method: A review of scientific databases was carried out to compile the products, data on the validation procedures and to verify their inclusion in the pharmacopeias. Results: Four trials were incorporated into the pharmacopeias. Statistical approaches included mainly regression assessment, ANOVA and Chi-square test. Conclusions: It is a challenge to conduct appropriate validation studies that are widely accepted by regulatory authorities, especially where validation centers have not yet been established. A clear indicator of this difficulty was the low number of methods for biological products incorporated into the guidelines.

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