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Optimisation of ultrafiltration for human serum albumin at NBI
Thesis (MEng)--Stellenbosch University, 2016.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2016
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| _version_ | 1867614054863863808 |
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| access_status_str | Open Access |
| author | Bhiman, Bradley |
| author2 | Gorgens, Johann F. |
| author_browse | Bhiman, Bradley Gorgens, Johann F. |
| author_facet | Gorgens, Johann F. Bhiman, Bradley |
| author_sort | Bhiman, Bradley |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MEng)--Stellenbosch University, 2016. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/98294 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:45:56.159Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2016 |
| publishDateRange | 2016 |
| publishDateSort | 2016 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/98294 Optimisation of ultrafiltration for human serum albumin at NBI Bhiman, Bradley Gorgens, Johann F. Bubb, Martin Stellenbosch University. Faculty of Engineering. Dept. of Process Engineering. Optimization Ultrafiltration Serum albumin Fractionation Blood proteins -- Separation National Bioproducts Institute -- South Africa UCTD Thesis (MEng)--Stellenbosch University, 2016. ENGLISH ABSTRACT: National Bioproducts Institute (NBI) is a key plasma fractionator within the Southern African countries. Human serum albumin (HSA), is the most abundant plasma protein in human blood and has significant physiological and therapeutic benefits. The global demand for HSA is steadily increasing and this has compelled plasma fractionators to optimize the key processes that are used to manufacture this plasma derived medicinal product (PDMP). A key process in the manufacture of HSA is the use of ultrafiltration (UF), a key membrane separation technology, to remove unwanted salts and solvents from the dissolved active pharmaceutical ingredient (API). UF of protein solutions consists of several key steps including first concentration step, diafiltration steps one to five and second concentration step. Ultrafiltration performance is limited by inherent process characteristics such as concentration polarization (CP) and membrane fouling (MF). During this study, the key factors that influence the UF of HSA namely protein concentration, ethanol concentration, temperature and ionic strength, were optimized within pre-defined ranges to evaluate their impact on permeate flux and membrane performance. Permeate flux is a key determinant of process time, which directly impacts annual production capacity with a particular UF unit (C200 UF rig). A key objective of this study was to maximize production capacity through optimization of the key factors above, using the C200 UF rig. The results of this study show that protein concentration is the key factor that influenced the various steps of UF of HSA and overall production capacity. The optimum protein concentration range for maximum productivity was 60.00g/L to 100.00g/L. The optimum protein concentration for UF of HSA was approximately 100.00g/L, determined using the gel concentration model. Ionic strength diafiltration diluent (1M – 3M) reduced permeate flux during UF of HSA. Ethanol (<10% v/v) also had a reducing effect on, permeate flux during UF of HSA, with the optimum range specified between 0% (v/v) to 7.75% (v/v). Optimum permeate flux is achieved at a temperature of 25°C for UF of HSA. The optimum protein concentration for UF is within the protein concentration range for optimum productivity. Further, the proposed increase in protein concentration during UF results in a greater than 30% increase when compared to the current batch size. AFRIKAANSE OPSOMMING: Die National Bioproducts Institute (NBI) is 'n belangrike bloed-plasma fraksioneerder in Suider-Afrika. Menslike serum albumien (MSA), is die plasma-proteïen in die grootste konsentrasie in menslike bloed, met beduidende fisiologiese en terapeutiese voordele. Die toenemende wêreldwye vraag na MSA het plasma fraksioneerders verplig om sleutel prosesse wat gebruik word om hierdie plasma-afgelei geneesmiddel te vervaardig, te verbeter. 'n Belangrike proses-stap in die vervaardiging van MSA is ultrafiltrasie (UF), 'n membraan-skeidingstegnologie wat gebruik word om ongewenste soute en oplosmiddels van die aktiewe farmaseutiese bestanddeel te verwyder. UF van proteïenoplossings bestaan uit verskeie opeenvolgende stappe, naamlik die eerste konsentrasie stap, diafiltrasie stappe 1 tot 5, en die tweede konsentrasie stap. Die werkverrigting van UF word tipies beperk deur meganismes soos konsentrasie polarisasie (KP) en membraan aankorsing (MA), inherent aan die membraan-filtrasie proses. In hierdie studie word die impak van die belangrikste proses-parameters op die UF van MSA proses ondersoek, naamlik proteïen-konsentrasie, etanol-konsentrasie, temperatuur en ioniese sterkte, binne ‘n vooraf-gedefinieerde operasionele gebied. Die impak hiervan op permeaat-deurvloei produksie-tempo en membraan prestasie is ëvalueer, met in agneming van KP en MA meganismes. Permeaat-deurvloei-tempo het ‘n kritiese invloed op die totale prosesseringstyd, wat 'n direkte impak jaarlikse produksie kapasiteit met 'n bepaalde UF eenheid het, in hierdie geval die C200 UF opstelling. 'n Belangrike doelwit van die huidige studie was om jaarlikse produksie kapasiteit te maksimeer, deur optimering van proseskondisies vir hierdie opstelling. Die eksperimentele resultate het getoon dat proteïenkonsentrasie is grootste invloed op die verskillende stappe in die UF van MSA, sowel as die jaarlikse produksie kapasiteit gehad het. Die voorkeur proteïen-konsentrasie vir 'n maksimum jaarlikse produksie kapasiteit was tussen 60 g/L en 100 g/L. ‘n Optimum proteïen-konsentrasie in hierdie gebied van 90 g/L tot 100 g/L, is bepaal deur toepassing van die konsentrasie polarisasie (gel konsentrasie) model. Aanpassing van die ioniese sterkte van die diafiltrasie verdunningsmiddel tot 1M-3M hetdie permeaat-deurvloei-temp verminder. Op soortgelyke wyse het toenames in die etanol tot by 10% (v/v) ook die deurvloei-tempo verminder, met ‘n verminderde effek in die voorkeur gebied van etanol konsentrasies tussen 0% (v/v) en 7.75% (v/v). Die voorkeur temperatuur vir maksimering van die permeaat-deurvloei-tempo was 25 °C, terwyl verdere toenames in temperatuur MSA-proteïen-onstabiliteit sal veroorsaak. Implementering van die voorgestelde verhoging in proteïen-konsentrasie tydens UF van MSA sal ‘n toename van meer as 30% in die grootte van ‘n enkellading deur die proses bewerkstellig, met dienooreenkomstige toenames in die jaarlikse produksie-kapasiteit. Masters 2016-03-09T14:01:56Z 2019-02-19T03:00:11Z 2016-03 Thesis http://hdl.handle.net/10019.1/98294 en_ZA Stellenbosch University 238 pages ; illustrations application/pdf application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Optimization Ultrafiltration Serum albumin Fractionation Blood proteins -- Separation National Bioproducts Institute -- South Africa UCTD Bhiman, Bradley Optimisation of ultrafiltration for human serum albumin at NBI |
| title | Optimisation of ultrafiltration for human serum albumin at NBI |
| title_full | Optimisation of ultrafiltration for human serum albumin at NBI |
| title_fullStr | Optimisation of ultrafiltration for human serum albumin at NBI |
| title_full_unstemmed | Optimisation of ultrafiltration for human serum albumin at NBI |
| title_short | Optimisation of ultrafiltration for human serum albumin at NBI |
| title_sort | optimisation of ultrafiltration for human serum albumin at nbi |
| topic | Optimization Ultrafiltration Serum albumin Fractionation Blood proteins -- Separation National Bioproducts Institute -- South Africa UCTD |
| url | http://hdl.handle.net/10019.1/98294 |
| work_keys_str_mv | AT bhimanbradley optimisationofultrafiltrationforhumanserumalbuminatnbi |