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[{"model": "core.projectfund", "pk": 31854, "fields": {"project": 7, "organisation": 7, "amount": 103932, "start_date": "2011-09-30", "end_date": "2015-09-29", "raw_data": 49831}}]
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[{"model": "core.projectfund", "pk": 22826, "fields": {"project": 7, "organisation": 7, "amount": 103932, "start_date": "2011-09-30", "end_date": "2015-09-29", "raw_data": 36354}}]
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[{"model": "core.projectfund", "pk": 14923, "fields": {"project": 7, "organisation": 7, "amount": 103932, "start_date": "2011-09-30", "end_date": "2015-09-29", "raw_data": 19}}]
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[{"model": "core.projectorganisation", "pk": 56743, "fields": {"project": 7, "organisation": 1997, "role": "PP_ORG"}}]
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[{"model": "core.projectorganisation", "pk": 56742, "fields": {"project": 7, "organisation": 1998, "role": "LEAD_ORG"}}]
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[{"model": "core.projectperson", "pk": 34947, "fields": {"project": 7, "person": 2348, "role": "RESEARCH_COI_PER"}}]
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| April 11, 2022, 3:44 a.m. |
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[{"model": "core.projectperson", "pk": 34946, "fields": {"project": 7, "person": 2349, "role": "PI_PER"}}]
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| April 11, 2022, 1:46 a.m. |
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{"title": ["", "BRIC DOCTORATE PROGRAMME - Understanding on-column protein aggregation and its impact on bioprocessing"], "description": ["", "\nVISION Chromatography is a ubiquitous unit operation in the purification of biopharmaceuticals yet few studies have addressed the biophysical characterisation of proteins at the solution-resin interface. This project aims to use advanced methods to characterise protein aggregation during adsorption/desorption stages under industrially relevant conditions to provide the basis for rational design. SIGNIFICANCE Biopharmaceuticals such as monoclonal antibodies (mAbs) are complex mixtures by nature and are susceptible to modifications during manufacture that can increase costs and development times and may ultimately prevent a molecule from being developed successfully. One pathway which is common to mAbs and other biopharamaceuticals is that of aggregation, which has to be controlled for product quality consistency and has also been linked to immunogenicity. Aggregation is therefore a common concern during development and manufacturing, particularly for liquid dosage forms. Rational design of product processing and formulation conditions would benefit greatly from improved understanding of aggregation phenomena. BACKGROUND Most of the approaches used to date for predicting aggregation rates implicitly assume bulk solution measurements and quantities are relevant e.g. the mid point unfolding temperature. However the importance of the liquid-solid, liquid-liquid, and air-liquid interface for protein aggregation is illustrated by the increasing number of studies that show aggregation can be accelerated by using agitation to entrain air or to increase exposure to solid-liquid interfaces, or insoluble liquids to create two phase systems. In addition to these studies of interfacial phenomena industrial groups report that chromatography elution during biopharmaceutical manufacture is of key concern for aggregation. In one study a leading group has taken the important example of protein A chromatography (used for mAb purification) and shown desorption from the resin exerted an added destabilising influence beyond that of the solution conditions. It is proposed this effect is related to structural changes in the product molecule during the events of adsorption and desorption. This complicates the examination of processing conditions and stabilising agents as they must be studied on-column rather than in simplified solution studies, for example in the same study certain agents were of benefit to product stability in solution but had a negative impact on-column. OBJECTIVES It is specifically these on-column adsorption/desorption phenomena this project is to study. The program aims to investigate this by looking at the following aspects. The first involves controlled variation of the adsorbent surface. This will be subdivided to examine; a) ligand type, using a common base matrix and solution conditions but differing ligands e.g. protein A and ion exchange moieties, b) the base matrix of the adsorbent, e.g. agarose vs. glass vs. methacrylate and c) pore size by using different porosity glass resins with the same ligand. The second facet is systematic manipulation of solution conditions again this can be subdivided into; a) manipulation of pH and salt to understand charge and hydrophobic effects and, b) investigation of stabilising agents (e.g. polysorbate, citrate and arginine). The critical final piece of the study will be the use of a range of protein's that display differing stability profiles. All these studies would be underpinned by the use of appropriate biophysical methods (electrophoresis (CE/IEF), HPLC/UPLC techniques, spectroscopic methods (CD, FTIR, DLS, fluorescence)), to understand the nature of the aggregation and structural changes taking place. When taken as a totality the above dataset will provide a comprehensive new perspective on those parameters critical to on-column aggregation allowing the mechanistic basis of the phenomena to be described and in turn providing the rationale for process design.\n\n"], "extra_text": ["", "\n\n\n\n"], "status": ["", "Closed"]}
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| April 11, 2022, 1:46 a.m. |
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{"external_links": [7]}
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| April 11, 2022, 1:46 a.m. |
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[{"model": "core.project", "pk": 7, "fields": {"owner": null, "is_locked": false, "coped_id": "71aeaaea-4a66-47aa-990c-2bfba5ce6017", "title": "", "description": "", "extra_text": "", "status": "", "start": null, "end": null, "raw_data": 7, "created": "2022-04-11T01:28:44.184Z", "modified": "2022-04-11T01:28:44.184Z", "external_links": []}}]
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