Characterization of Polysorbate Ester Fractions and Implications in Protein Drug Product Stability

The aim of this study is the identification, structural characterization, and qualification of a degradation impurity of bisoprolol labeled as Impurity RRT 0.95. This degradation product is considered as a principal thermal degradation impurity identified in bisoprolol film-coated tablets. The impurity has been observed in the stress thermal degradation study of the drug product. Using HPLC/DAD/ESI-MS method, a tentative structure was assigned and afterwards confirmed by detailed structural characterization using NMR spectroscopy. The structure of the target Impurity RRT 0.95 was elucidated as phosphomonoester of bisoprolol, having relative molecular mass of 406 (positive ionization mode). The structural characterization was followed by qualification of Impurity RRT 0.95 using several different in silico methodologies. From the results obtained, it can be concluded that no new structural alerts have been generated for Impurity RRT 0.95 relative to the parent compound bisoprolol. The current study presents an in-depth analysis of the full characterization and qualification of an unidentified impurity in a drug product with the purpose of properly defining the quality specification of the product.

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Synthesis and characterization of heparin conjugated Tetronic®–PCL copolymer for protein drug delivery

Current Applied Physics ◽

10.1016/j.cap.2006.11.014 ◽

2007 ◽

Vol 7 ◽

pp. e49-e52 ◽

Cited By ~ 10

Author(s):

Jung Seok Lee ◽

Dong Hyun Go ◽

Jin Woo Bae ◽

In Kwon Jung ◽

Joon Woo Lee ◽

...

Keyword(s):

Drug Delivery ◽

Synthesis And Characterization ◽

Protein Drug ◽

Protein Drug Delivery

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Biochemical Characterization of a Recombinant FIX Drug Candidate for Treatment of Hemophilia B

Blood ◽

10.1182/blood.v116.21.4658.4658 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4658-4658

Author(s):

Peter Turecek ◽

Susanne Vejda ◽

Katalin Varadi ◽

Hanspeter Rottensteiner ◽

Ernst Boehm ◽

...

Keyword(s):

Biochemical Characterization ◽

Drug Product ◽

Coagulation Factor ◽

Factor Ix ◽

Hemophilia B ◽

Drug Candidate ◽

Alternative Drug ◽

Recombinant Factor Ix ◽

Fermentation Technology

Abstract Abstract 4658 Human coagulation factor IX (FIX) is a vitamin-K-dependent coagulation factor whose absence or dysfunction causes hemophilia B. Treatment of hemophilia B is based on replacement therapy using highly purified FIX concentrates. Baxter has developed a recombinant factor IX for treating hemophilia B patients that is produced in a CHO cell-line using a serum and protein-free fermentation technology. The purification process avoids the use of immune-affinity chromatography and includes two viral reduction steps. The final drug product is formulated in the absence of proteins of animal or human origin. Baxter's recombinant FIX resembles commercially available rFIX in most characteristics with the exception of a significantly lower FIXa content, which might improve standardization compared to commercial rFIX products. Preclinical and clinical lots of rFIX were characterized with respect to their hemostatic potency, efficiency of activation by FXIa and FVIIa in the presence of tissue factor, and capacity to bind to phospholipid vesicles. Three lots of commercial rFIX with different potencies and one lot of a plasma-derived FIX product were included in the study. Similarity could be shown between the preclinical and clinical lots of rFIX in all these assays. Furthermore, the functional and biochemical characterization of Baxter's recombinant FIX showed that it resembles the recombinant comparator product. The phase I clinical trial which has been initiated will now have to show whether Baxter's rFIX can become an alternative drug candidate product for treating patients suffering from hemophilia B. Disclosures: Turecek: Baxter Innovations GmbH: Employment. Vejda:Baxter Innovations GmbH: Employment. Varadi:Baxter Innovations GmbH: Employment. Rottensteiner:Baxter Innovations GmbH: Employment. Boehm:Baxter Innovations GmbH: Employment. Reiter:Baxter Innovations GmbH: Employment. Kaliwoda:Baxter Innovations GmbH: Employment. Mundt:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment.

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Determination and Characterization of Two Degradant Impurities in Bendamustine Hydrochloride Drug Product

Journal of Chromatographic Science ◽

10.1093/chromsci/bmv070 ◽

2015 ◽

Vol 53 (10) ◽

pp. 1673-1679

Author(s):

Wenhua Chen ◽

Limin Zou ◽

Fei Zhang ◽

Xiangyang Xu ◽

Liandi Zhang ◽

...

Keyword(s):

Drug Product

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Integration of Regulatory Guidelines into Protein Drug Product Development

PDA Journal of Pharmaceutical Science and Technology ◽

10.5731/pdajpst.2015.005553 ◽

2016 ◽

Vol 70 (1) ◽

pp. 2-11

Author(s):

W. Wang

Keyword(s):

Product Development ◽

Drug Product ◽

Protein Drug ◽

Regulatory Guidelines

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Identification, Isolation and Origin of Potential Dimer Impurities of Dichlorphenamide: A Carbonic Anhydrase Inhibitor Drug (Antiglaucoma)

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23166 ◽

2021 ◽

Vol 33 (6) ◽

pp. 1249-1252

Author(s):

T. Purendar Reddy ◽

Nageshwar Dussa ◽

Srinivas Mamidi ◽

Mahesh Panasa ◽

Ramadas Chavakula ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Drug Product ◽

Carbonic Anhydrase Inhibitor ◽

Drug Substance ◽

Substantial Impact ◽

Isolation And Characterization ◽

New Process ◽

Inhibitor Drug

Present work describes the identification, isolation and characterization of two new process related dimeric impurities of dichlorphenamide (1). During the synthesis of dichlorphenamide, the formation of two new dimeric impurities namely 2,3-dichloro-5-(3,4-dichloro-5-sulfamoyl-phenyl)sulfonylbenzenesulfonamide (2) (1,1Œ-dichlorphenamide dimer) and 2,3-dichloro-5-(2,3-dichloro-5-sulfamoylphenyl) sulfonyl-benzenesulfonamide (3) (1,3Œ-dichlorphenamide dimer) was observed. In addition, origin and the strategies adapted to control these potential dimer impurities were also described. These impurities have a substantial impact on the quality of the drug substance as well as drug product.

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Development and validation of stability-indicating RP-HPLC method for determination of Olmesartan medoxomile in pharmaceutical dosage form and identification, characterization of alkaline degradation impurity of Olmesartan medoxomile drug substance as well as drug product

Chemical Industry and Chemical Engineering Quarterly ◽

10.2298/ciceq111204035j ◽

2012 ◽

Vol 18 (4-1) ◽

pp. 595-604 ◽

Cited By ~ 2

Author(s):

P.S. Jain ◽

A.J. Chaudhari ◽

S.J. Surana

Keyword(s):

Degradation Product ◽

Drug Product ◽

Olmesartan Medoxomil ◽

Hplc Method ◽

Drug Substance ◽

Alkaline Degradation ◽

Stability Indicating ◽

Rp Hplc

Olmesartan Medoxomil (OLME) belongs to a group of angiotensin II receptor blockers used as an antihypertensive agent and is currently being used for prevention of Hypertension. This paper describes the Validation and development of stability indicating RP-HPLC method for the determination of OLME in the presence of its degradation products generated from forced degradation study and characterization of degradation product (impurity). The assay involved gradient elution of OLME on An LC GC BDS C18 column (250 ? 4.5mm, 5-?m particle size) was employed for loading the sample. The mobile phase A consists of 7 ml Triethylamine in 1000 ml water (pH adjusted to 3.0 with orthophosphoric acid) and B contains acetonitrile. Quantification was achieved with photodiode array detection at 257 nm. The chromatographic separation was obtained with a retention time of 6.72 min, and the method was linear in the range 50-150 ?g/ml. The method was validated according to the ICH guidelines with respect to linearity, precision, accuracy, limit of detection (LOD), limit of quantification (LOQ), specificity and robustness. Impurity found in stressed and stability studies of Olmesartan Medoxomil in both drug substance and drug product are described. This degradation product is identified as 1-(biphenyl-4-ylmethyl)-1H-imidazole-5-carboxylic acid. An Alkaline degradation pathway of Olmesartan medoxomil, for the formation of this degradation product, has been proposed and degradation product was characterized.

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