Advanced Optimization,
Implementation, and Scale Up
of Tangential Flow Filtration
This high level course explores the implementation of cutting-edge tangential flow filtration (TFF) techniques and technologies. This course includes a choice of technically rigorous modules which address high-level scientific concerns within tangential flow filtration design and implementation, including high-viscosity tangential flow filtration (HVTFF), single-pass tangential flow filtration design (SPTFF) and operation, and two-pump microfiltration (MFTFF).
There is an increasing need for high concentration biopharmaceuticals. Tangential flow filtration is typically used to concentrate the drug substance, and this module addresses the many challenges associated with conducting very high-concentration endpoint tangential flow filtration operations. This module evaluates why high-concentration tangential flow filtration processes are difficult to implement and how these challenges can be surmounted during process development.
Single-pass tangential flow filtration has been proposed as an effective unit operation for concentration of product either continuously or for products where multiple pump passes are unacceptable. This module addresses the background and capabilities of SPTFF together with implementation strategies.
Microporous and “open UF” tangential flow filtration operations are commonly used for primary or secondary clarification of products, such as lysates and cell cultures. These highly permeable membranes can lead to very high initial conversions but poor fluxes over the length of the process. This module investigates why this phenomenon occurs and provides novel system design strategies to prevent it.
The courses are modular and can be selected individually or in combination with each other.
- Awareness of new process demands on the tangential flow filtration unit operation
- Fully understanding the theoretical and practical implications of advances in tangential flow filtration
- Implementation and development of tangential flow filtration techniques and processes
The laboratory exercise takes place using a realistic feed stream and typical process conditions. Depending on the advanced modules chosen, the laboratory sessions may include:
- Optimising tangential flow filtration microfiltration and highly permeable ultrafiltration processes using permeate control
- Successfully operating very high-concentration tangential flow filtration processes
- Implementation of single-pass tangential flow filtration
- This course is designed for technically capable engineers, scientists and managers within the biopharmaceutical industry who are responsible for designing, implementing and troubleshooting large-scale TFF systems for possible or current clinical manufacture.
- A copy of the course materials
- Protocol and results of laboratory sessions
- Explain the hydrodynamics and rheology which influences pressure drops in tangential flow filtration processes
- Explain the challenges and strategies employed to successfully process high-viscosity products using tangential flow filtration
- Describe phenomena which can occur at high concentrations, such as the Donnan effect
- Operate and optimize processes with highly concentrated material in the laboratory
- Explain the theory of SPTFF and how it differs from conventional TFF processes
- Explain the applications of SPTFF and where it is appropriate to place in a process
- Explain the optimization of SPTFF and how it differs from conventional TFF optimization
- Carry out SPTFF in the laboratory and analyse the data
- Explain the theory of TFF-MF and how it differs from TFF-UF processes
- Explain the challenges in optimising TFF-MF processes and how to mitigate them
- Operate and optimize a TFF-MF process in the laboratory and analyse the data
- Welcome and course introduction
- HVTFF theory
- Processing challenges
- Practical operative recommendations
- High protein concentration phenomena (Donnan effect)
- Practical session
- Assessment
- Welcome and course introduction
- SPTFF principles
- Value and use
- Process development and implementation
- Case studies
- Practical session
- Welcome and course introduction
- MFTFF theory
- Operating parameter optimization
- Scale-up
- Practical session
- Assessment