Separations, Downstream Processing and Bioanalytical Science

Overview

Summary of Lecture Content:

This module contains the methods and principles behind separations, the fundamental theories behind separating substances based on polarities and chemical properties. Filtration when applied to a biopharmaceutical process and the subsequent purification of the crude product via downstream processing. Finally the analysis when applied to biopharmaceuticals in terms of spectroscopic techniques and assays will be discussed and examples given.

Series 1: Separations
This block looks at the different methods which are employed for the separations of compounds based on their physical properties in terms of size, polarity, charge etc. Analytical and preparative chromatography using various different techniques will be discussed and students will be expected to recall these methods including the pros and cons. The use of electrophoresis for the separation of proteins is also discussed.
Series 1 Lectures:
• Lecture 1: Analytical Chromatography
• Lecture 2: Preparative Chromatography
• Lecture 3: Interactions and Polarity
• Lecture 4: Electrophoresis

Series 2: Filtration
This block looks at and discusses the importance of filtration in the biopharmaceutical process in terms of the methods employed including ultrafiltration and also the mathematical models involved in maximising the efficiency of a filtration system. The materials and types of filter used in the filtration process will also be discussed and why these different materials are key for obtaining a maximal filtration system.
Series 2 Lectures:
• Lecture 5: Principles of Filtration
• Lecture 6: Types and Materials of a Filter
• Lecture 7: Microfiltration vs. Ultrafiltration
• Lecture 8: Modelling Filtration Mathematically

Series 3: Downstream Processing
This block examines the different methods employed for the chromatographic separation of proteins, how this is done and also what the properties and classification behind the stationary phase are. Design of chromatographic columns will be discussed in detail and the methods for which a column should be packed and which combination of stationary phases are best for obtaining a high purity biopharmaceutical product.
Series 3 lectures:
• Lecture 9: Preparative Protein Chromatography (PPC)
• Lecture 10: Stationary Phase- Properties, Classification and Concepts
• Lecture 11: Types of Chromatography in PPC
• Lecture 12: Design of Chromatography Columns

Series 4: Bioanalytical Science
The discussion in this block centres around the analysis of the purified protein following the production and downstream processing, the analytical techniques employed and how the techniques used can provide information on the purity of the product. How these methods of analysis are used in an industrial plant and why it is important to ensure there is no chance of variation between batches of the biopharmaceutical produced.
Series 4 lectures:
• Lecture 13: Protein and Peptide Analysis
• Lecture 14: Hyphenated and Non-hyphenated Techniques
• Lecture 15: Ligand Binding Assays
• Lecture 16: NMR
Summary of Workshops
• Workshop 1: This workshop will focus mainly on the interactions an analyte would have and why this is important on the chromatographic separation, the methods of separation for preparative and analytical chromatography are discussed and some examples of which would be appropriate for a certain scenario
• Workshop 2: This workshop will mainly focus on the mathematical modelling when applied to a filtration system and why it is important to model it in this way to maximise the amount of filtration while remaining productive at the same time
• Workshop 3: This workshop will centre around the design of chromatography columns which would be used in an industrial setting and also the appropriate choice of stationary phase based o they types of interactions which would best separate the pure product from any present impurities
• Workshop 4: This workshop will align with Workshop 1 whereby the use of analytical procedures in particular the hyphenated and non-hyphenated techniques can be discussed and demonstrated using the Pharmaceutical Analysis suite

Summary of Module Delivery:
This block will be delivered in-person and also via recorded workshops which students can use in their own revision and study time to refer to. As there is an element of mathematics and advanced analytical techniques which will be complex to students with no background in the field workshops will be provided to allow time for discussion and work through examples in groups. It is envisioned that these workshops will be held in person and also online and be recorded and uploaded to Teams so students can refer to during their own studies.

Learning Objectives

At the end of the module students will be able to:
• Recognise and describe the process behind separations both on an analytical and preparative scale
• List the physical properties which determine the effectiveness of a separation technique
• Describe the methods of downstream processing in terms of the chromatography stationary phases and types of column
• Understand thee processes behind protein and peptide analysis, why this is important and why it is key to eliminate the possibility of major variation
• Understand the operation and interpretation of analytical results of protein analysis in terms of hyphenated and non-hyphenated techniques including HPLC, GC, LC-MS, GC-MS, ICP-MS, CE-MS
• Model mathematically the most effective form of filtration for the separation of a protein from the living cell

Skills

Skills Associated with Module:
• Core skills in underlying physical sciences, in particular physics and chemistry as applied to solving problems
• Logical thinking
• STEM skills
• Communication and reporting writing skills
• Mathematical problem solving ability

Assessment

Course Requirements:
Coursework submission: 100%
Total Coursework elements must be passed at: 50%