Full Title:Biopharmaceutical Processing (Downstream)
Module Code:PHAR S8008
 
Credits: 7.5
Valid From:Semester 1 - 2013/14 ( September 2013 )
Module Delivered in 2 programme(s)
Module Description:The aim of this module is to provide students with an in-depth knowledge of the downstream processing of biopharmaceuticals (both theoretical and practical topics pertaining to the isolation/purification and manufacture of biopharmaceuticals).
Learning Outcomes:
On successful completion of this module the learner should be able to
  1. Distinguish processes for initial biopharmaceutical recovery on the basis of whether the product is intracellular or extracellular.
  2. Compare and contrast large scale chromatography techniques for the recovery, purification and concentration of biopharmaceuticals.
  3. Compare and contrast filtration systems for recovery, concentration and risk reduction of biopharmaceuticals.
  4. Evaluate both theoretical and practical aspects of finished product characterisation and have a working knowledge of all associated analytical techniques.
  5. Discuss and convey the validation requirements of regulatory authorities relating to biopharmaceutical processing.
 

Module Content & Assessment

Indicative Content
Initial Biopharmaceutical Recovery
Extracellular biopharmaceutical product recovery - preparative centrifugation (Disk-Stack, Tubular Bowl, Basket centrifuge) or MicroFiltration (Normal Filtration versus Tangenital Flow Filtration; Operation Mode -Batch or Continuous). Intracellular Biopharmaceutical Recovery- Cell disruption (Physicomechanical - Homogenisation, Bead Mill, Rotor-Stator Mill or Chemical - lysozyme, detergents) followed by centrifugation or filtration.
Chromatographic Purification
Selection of a purification regime. Range of available chromatographic systems (Ion-Exchange, Gel Filtration, Affinity Chromatography) at laboratory and industrial levels. Design, operation and maintenance of process-scale chromatography systems. Extraction and precipitation of biopharmaceutical product.
Filtration and membrane processes
Normal versus Tangenital Flow Filtration. Micro, Ultra and Nanofiltration techniques and applications. Membrane module types (Stirred Cell, Flat Sheet Tangential Flow (TF) Module, Spiral Wound, Tubular and Hollow Fibre Membrane Modules. Use of ultrafiltration and nanofiltration for minimisation of destructive influences during downstream processing - removal of virus particles. Other membrane processes -Dialysis, Reverse Osmosis.
QC functions in downstream processing
In-process and final product testing. Detection and determination of yield, purity and biological activity. Detection and quantification of excipients and all other expected components. Physical characterisation of final product and detection of product impurities. Approaches to contaminant removal.
Experimental Work:
The following list is designed to serve as an illustration of possible practical exercises which would illustrate key concepts and techniques. Many of the practical situations are applicable to a range of biopharmaceutical products and so have a broad spectrum of merit. • Fractionation and homogenisation of rabbit liver tissue for isolation of macromolecules using differential centrifugation and sedimentation. Investigation of isolated marcomolecular (mitochondria) activity using specific enzyme assays (lactate dehydrogenase assay) and protein assays. • Separation of proteins from sheep blood using gel filtration chromatography. • Extraction and purification via ion exchange chromatography, activity assay and agarose electrophoresis of a selected enzyme e.g. restriction enzyme ECO R1. • Extraction of Concanavalin A, a carbohydrate-binding lectin protein, from jack bean meal using enzymatic disruption, purification via affinity chromatography. Biological activity determination of the isolated protein using an immunoblot enzyme assay. Assessment of protein purity using SDS-PAGE electrophoresis.
Assessment Breakdown%
Course Work50.00%
End of Module Formal Examination50.00%

Full Time

Course Work
Assessment Type Assessment Description Outcome addressed % of total Marks Out Of Pass Marks Assessment Date Duration
Practical/Skills Evaluation Students will be required to submit regular typed laboratory reports. Marks for reports will be based on a student's ability to record preliminary data, calculate derivatives from these, display data, comment on their meaning in the context of the actual experiment and associated theory, and discuss limitations to the experiment and results obtained. Reports will be maintained according to document control under GMP. 1,2,3,4 30.00 0 0 Every Week 0
Written Report Students will produce a report and numerically evaluate set tasks following a 1 day specialised workshop in the National Institute for Bioprocessing Research and Training (NIBRT) in UCD. During the workshop, students will perform and evaluate 2 different areas of large-scale downstream processing eg large scale chromatography, ultrafiltration. Students will be assessed on their understanding of the prescribed techniques including a comparison of of processes from laboratory to industrial scale. 2,3,4,5 20.00 0 0 Week 26 0
No Project
No Practical
End of Module Formal Examination
Assessment Type Assessment Description Outcome addressed % of total Marks Out Of Pass Marks Assessment Date Duration
Formal Exam End-of-Semester Final Examination 1,2,3,4,5 50.00 0 0 End-of-Semester 0
Reassessment Requirement
A repeat examination
Reassessment of this module will consist of a repeat examination. It is possible that there will also be a requirement to be reassessed in a coursework element.

DKIT reserves the right to alter the nature and timings of assessment

 

Module Workload & Resources

Workload: Full Time
Workload Type Workload Description Hours Frequency Average Weekly Learner Workload
Lecture No Description 2.00 Every Week 2.00
Practical No Description 3.00 Every Week 3.00
Tutorial No Description 1.00 Every Week 1.00
Directed Reading No Description 3.00 Every Week 3.00
Independent Study No Description 3.00 Every Week 3.00
Total Weekly Learner Workload 12.00
Total Weekly Contact Hours 6.00
This course has no Part Time workload.
Resources
Recommended Book Resources
  • Walls and Loughran 2011, Protein Chromatography “Methods and Protocols”, 2011, Humana Press [ISBN: 9781607619123]
  • Michael Gromiha 2010, Protein Bioinformatics (from sequence to function), Academic Press [ISBN: 9788131222973]
  • Walsh, G. 2007, Pharmaceutical biotechnology: Concepts and applications, J. Wiley and Sons [ISBN: 9780470012444]
  • Ghosh 2006, Principles of Bioseparations Engineering, World Scientific Publishing [ISBN: 9812568921]
  • Various 2004, ISPE baseline guide for biotechnology, ISPE
  • Petsko, G.A. and Ringe, D. 2004, Protein structure and function, Blackwell Press
  • Walsh, G. 2003, Biopharmaceuticals: Biochemistry and biotechnology., J. Wiley and Sons
  • Nash, R.A. and Wachter, A.H. 2003, Pharmaceutical process validation, 2nd Ed., Marcel Dekker
  • Roe, S. 2001, Protein purification techniques : A practical approach, Oxford University Press
  • Reinhard Renneberg, Biotechnology for Beginners, Academic Press [ISBN: 9783827418470]
  • Clark and Pazdernik, Biotechnology, Academic Cell [ISBN: 9780123850638]
Recommended Article/Paper Resources
  • Bangaru Balasundaram, Sue Harrison and Daniel G. Bracewell 2009, Advances in product release strategies, Trends in Biotechnology, 27, 477-485
  • Hage et al. 2009, Characterisation of drug protein interactions - Affinity Chromatography, J Sep Sci, 31, 835 - 853
  • Wen-Chien Lee and Kelvin H. Lee 2004, Analytical Biochemistry, Applications of affinity chromatography in proteomics, 324, 1-10
Other Resources

Module Delivered in

Programme Code Programme Semester Delivery
DK_SBIOP_8 Bachelor of Science (Honours) in Biopharmaceutical Science 2 Mandatory
DK_SBIOP_8a Diploma in Biopharmaceutical Processing 2 Mandatory