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dc.contributor.advisorForrest, Marcus L
dc.contributor.authorKleindl, Peter Alan
dc.date.accessioned2017-01-02T19:52:36Z
dc.date.available2017-01-02T19:52:36Z
dc.date.issued2016-08-31
dc.date.submitted2016
dc.identifier.otherhttp://dissertations.umi.com/ku:14885
dc.identifier.urihttp://hdl.handle.net/1808/22336
dc.description.abstractRegulatory approval of follow-on biologics and other generic versions of complex pharmaceutics requires that a potential biosimilar (test) product demonstrates similarity to an innovator (reference) product through a stepwise, totality of the evidence approach. Although the best statistical approaches for assessing analytical similarity are still under debate, these investigations rely heavily upon comparability of a given pharmaceutical’s critical quality attributes (CQAs) – physicochemical and biological properties that are most relevant to clinical safety and efficacy. Selection of proper CQAs from the large amounts of physical, chemical, and biological data needed for sufficient characterization of these kinds of pharmaceutics can be difficult due to their inherent complexity and heterogeneity. Crofelemer, a botanically sourced polymeric proanthocyanidin, exhibits significant variation in final drug product resulting from processing and purification of the raw material and the botanical nature of the crude source material. From a single lot of crofelemer, various physically and chemically degraded samples were produced in an effort to create artificial lots with varying “similarity” to the reference starting material. Physical, chemical, and biological variability of the original and artificial lots were investigated using a variety of spectroscopic, chromatographic, mass-spectrometry, and biological techniques. The entirety of the analytical data collected for each crofelemer lot was then utilized in a machine learning approach to identify individual and/or combinations of CQAs which can accurately identify and distinguish subtle variations between the complex drug product (crofelemer) and the artificial lots comprised of its adulterated forms.
dc.format.extent52 pages
dc.language.isoen
dc.publisherUniversity of Kansas
dc.rightsCopyright held by the author.
dc.subjectPharmaceutical sciences
dc.subjectBiomedical engineering
dc.subjectAnalytical chemistry
dc.subjectBiosimilar
dc.subjectComplex therapeutics
dc.subjectCritical quality attributes
dc.subjectCrofelemer
dc.subjectNMR
dc.subjectSecretory diarrhea
dc.titleCharacterization of the oligomeric proanthocyanidin crofelemer toward development of an integrated mathematical model for comparison of complex molecules
dc.typeThesis
dc.contributor.cmtememberMiddaugh, Charles R
dc.contributor.cmtememberYang, Xinmai
dc.thesis.degreeDisciplineBioengineering
dc.thesis.degreeLevelM.S.
dc.identifier.orcid
dc.rights.accessrightsopenAccess


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