Atanas Koulov
Hoffmann-La Roche
ParticleProtein aggregationMicroscopyNanotechnologyBiochemical engineeringChemistryParticle sizeMaterials scienceIn vivoPolysorbateCharacterization (materials science)ImmunogenicityPolysorbatesFlow imagingParticle analysisAntibodies monoclonalLight obscurationDrug productPharmacology toxicologyComputer scienceChromatographyMonoclonal antibody
29Publications
13H-index
533Citations
Publications 29
Newest
#1Ariane Schröter (University of Basel)H-Index: 1
#2Hanns-Christian Mahler (Goethe University Frankfurt)H-Index: 31
Last. Michael JahnH-Index: 3
view all 6 authors...
Abstract null null Introduction: The migration of chemicals from processing materials into biopharmaceuticals can lead to various problems. Leachables from administration materials, with no possibility of further clearance, are of particular concern. Released chemicals can be toxic or react with formulation components, thereby impacting product safety. Therapeutic proteins, which are susceptible to chemical modifications, have highest risk to be affected. null Aim: The aim of this study was to i...
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#1Ariane Schröter (University of Basel)H-Index: 1
#2Sonja Peter (ETH Zurich)
Last. Michael JahnH-Index: 3
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Abstract null null Leaching of toxic or reactive chemicals from polymeric materials can adversely affect the quality and safety of biopharmaceuticals. null It was therefore the aim of the present study to analyze leachables from a disposable clinical administration syringe using a polysorbate-containing surrogate solution and to assess their chemical reactivity. null Analytical methods did include (headspace) GC-MS, Fourier-transform-infrared spectroscopy, a ferrous oxidation-xylenol orange assa...
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#1Ariane Schröter (University of Basel)H-Index: 1
#2Atanas KoulovH-Index: 13
Last. Michael JahnH-Index: 3
view all 5 authors...
Abstract Introduction Polysorbates (PS) are used in biopharmaceuticals to stabilize therapeutic proteins. Oxidative degradation of (poly)unsaturated fatty acids (PUFAs) contained in PS was shown to lead to α,β-unsaturated carbonyls. Aim The n-6-PUFA linoleic acid accounts for up to 18% of all FAs contained in multi-compendial grade PS80. 4-hydroxynonenal (HNE) is highly reactive towards nucleophilic amino acids, potentially leading to covalent protein modifications. This study tests whether HNE ...
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Abstract Intravitreal (IVT) injection is currently the state of the art for drug delivery to the back of the eye. Drug Products (DP) intended for IVT injections usually pose challenges such as a very low injection volume (e.g. 50 μL) and high injection forces. DPs in vials are typically transferred and injected using disposable polymer syringes, which can feature a silicone oil (SO) coating. In our syringe in-use study, we compared dead volume, total SO content and SO layer distributions of thre...
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#1Joachim Schuster (University of Basel)H-Index: 3
Last. Roman MathaesH-Index: 10
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Abstract In recent years, the stability of biotherapeutics in vivo has received increasing attention. Assessing the stability of biotherapeutics in serum may support the selection of adequate molecule candidates. In our study, we compared the physical stability of 8 different monoclonal antibodies (mAbs) in phosphate-buffered saline (PBS) and human serum. mAbs were Alexa Fluor 488-labeled and characterized with respect to fragmentation, aggregation, and proteinaceous particle formation. Samples ...
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#1Michael JahnH-Index: 3
#2Andreas ZerrH-Index: 1
Last. Hanns-Christian MahlerH-Index: 31
view all 6 authors...
Polysorbates are critical stabilizers in biopharmaceutical protein formulations. However, they may degrade in drug substance (DS) or drug product (DP) during storage. Degradation catalyzed by lipases present in host cell proteins (HCPs) is one suspected root cause. The purpose of this study was to develop an assay to detect lipolytic activity in biopharmaceutical DS and DP formulations. The assay is based on the hydrolysis of the lipase substrate 4-methylumbelliferyl oleate to yield the fluoresc...
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#1Ariane Schmidt (Goethe University Frankfurt)H-Index: 1
#2Atanas KoulovH-Index: 13
Last. Michael JahnH-Index: 3
view all 5 authors...
PURPOSE: Polysorbates are stabilizers typically required in therapeutic protein formulations. Due to their chemical structure, polysorbates are prone to degradation, which can render a pharmaceutical product instable or incompliant. The purpose of this study was to investigate if the addition of butylhydroxytoluene (BHT) and butylhydroxyanisole (BHA) protects Polysorbate 20 (PS20) and Polysorbate 80 (PS80) against oxidative degradation. METHODS: PS20 and PS80 solutions containing BHA, BHT - or a...
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#1Joachim Schuster (University of Basel)H-Index: 3
#2Atanas KoulovH-Index: 13
Last. Roman MathaesH-Index: 10
view all 8 authors...
Abstract In recent years, an increasing number of studies assessed the stability of biotherapeutics in biological fluids. Such studies aim to simulate the conditions encountered in the human body and investigate the in vivo stability under in vitro conditions. However, due to complexity of biological fluids, standard pharmaceutical methods are poorly suited to assess the stability of biotherapeutics. In this study, a fluorescent-labeled therapeutic immunoglobulin G (IgG) was analyzed for protein...
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#1Joachim Schuster (University of Basel)H-Index: 3
#2Atanas KoulovH-Index: 13
Last. Roman MathaesH-Index: 10
view all 7 authors...
: A manuscript version without peer-review revisions was mistakenly processed and published.
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#1Joachim Schuster (University of Basel)H-Index: 3
#2Atanas KoulovH-Index: 13
Last. Roman MathaesH-Index: 10
view all 7 authors...
Significant efforts are made to characterize molecular liabilities and degradation of the drug substance (DS) and drug product (DP) during various product life-cycle stages. The in vivo fate of a therapeutic protein is usually only considered in terms of pharmacokinetics (PKs) and pharmacodynamics (PDs). However, the environment in the human body differs substantially from that of the matrix (formulation) of the DP and may impact on the stability of an injected therapeutic protein. Stabilizing e...
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