Advanced Course

Downstream Processing

Course description

The challenge for biochemical engineers is to design compact and clean processes to efficiently separate instable products, such as recombinant proteins, from dilute complex fermentation broths to the required pharmaceutical degree of purity. Therefore, the quantitative systematic design of integrated downstream processes is the general theme of this Advanced Course. The aim of the course is to provide the tools for the participants to be able to quantitatively and systematically design an integrated downstream process. This course has been organised since 1989.

3 – 7 July 2023

Delft University of Technology, the Netherlands

Note: A limited number of fellowships is available for PhD students (reduced fee).


Advanced Course Downstream Processing

This intensive course consists of theoretical and applied lectures, exercises, case studies and computer simulations. The course will be given in English. A laptop and pocket calculator is required.

The course presents the state of the art in downstream processing of biotechnological products. It provides knowledge of different techniques for solid-liquid separation, product release, refolding, concentration and purification of precious biotechnology products with a focus on the total integrated process. An international group of experts from both industry and academia will lecture to assure an optimal balance of practical knowledge and theoretical insight, which subsequently will be trained by exercises, into the quantitative engineering aspects of bioseparations. At the end of the course, the participants should be able to estimate main equipment dimensions, know qualitative constraints to the integrated bioprocess and have a quantitative insight in process streams, structure and economics.

The course starts with an overview of possibilities and problems typically associated with the recovery of bioproducts. Physico-chemical characteristics of the products, as well as the fermentation broth with its multiple contaminants, are discussed in relation to possibilities for selective separation. Using this information, the general structure of large scale industrial processes will be outlined.

The thermodynamical basics and biochemical engineering principles will be introduced and developed during the course related to bio-separations. Special attention will be paid to the unit operations typically used in this field of industry. Firstly, various solid-liquid separation techniques and cell disruption will be treated. Particular consideration will be given to the application of major concentration techniques such as extraction, adsorption and membrane separation. Furthermore, the scientific and industrial aspects of purification by means of precipitation and chromatography will be discussed. In addition, the release of intracellular products as well as protein folding in industrial protein processes will be discussed.

Process integration is the binding element in the course. During the course, a case study on the design of an integrated purification process for a recombinant protein will offer the participants the opportunity to practice on the individual unit operations as well as on the integrated process. Finally, possibilities of computer-aided, rational design of integrated separation processes will be demonstrated.

Study load

The course (including preparatory materials) is valued 41 hours of work.

Who should attend?

This Advanced Course is aimed at professionals (MSc or PhD level is required) in (bio)chemical engineering, or in microbiology or biochemistry with a basic knowledge in chemical engineering. The course is primarily aimed at those already employed in industry and who are interested in the separation of biotechnological products. In addition, this Advanced Course is an option in the two-year postgraduate programs of Delft University of Technology.


Monday 3 July 2023
Theme: Today’s bioseparation processes.
Mechanical separations: solid-liquid separation
08:45 Registration
09:00 Opening
09:10 Introduction to the separation processes: Pitfalls and challenges in bioseparation processes
  Luuk van der Wielen
10:00 Engineering fundamentals: Mass balances: from batch to continuous counter current processes
  Luuk van der Wielen
11:15 Case study: industrial protein production (I)
  Marcel Ottens and Exercise Assistants
12.30 Lunch
13:30 Solid-liquid separation: filtration and centrifugation
  Marcel Ottens
14:15 Assignment: design of filtration equipment
  Marcel Ottens and Exercise Assistants
15:15 Predicting molecular properties. Molecular properties and selection of separation conditions: Equilibrium calculations
  Luuk van der Wielen
16:15 Case study: industrial protein production (II)
  Marcel Ottens and Exercise Assistants
18:00 Social drink and buffet

Tuesday 4 July 2023
Theme: Mechanical separations: solid liquid separation. Concentration and design
09:00 Centrifugation in the biopharmaceutical industry. Design considerations of sedimentation and centrifugation processes: from biomass removal to centrifugal extraction
  Eduardo Lau
10:30 Assignment: centrifugation
  Marcel Ottens and Exercise Assistants
11:30 L-L Extraction & Aqueous two face extraction
  Raquel Aires Barros
12.45 Lunch
13:45 Assignment: extraction
  Marcel Ottens and Exercise Assistants
14:45 Membrane technology: theory, design & industrial application
  Reinoud Noordman
16:15 Case study: industrial protein production (III)
  Marcel Ottens and Exercise Assistants
18:05 Lab tour: High Throughput Facilities (optional)
19:00 Social Drink & Poster presentation from department

Wednesday 5 July 2023
Theme: Purification processes
09:00 Design of chromatographic separations. Equilibrium theory and column design Non-linear and mass transfer effects
  Marcel Ottens
10:15 Assignment: ultrafiltration
  Marcel Ottens and Exercise Assistants
11:15 Large-scale Continuous Chromatography and Simulated Moving Bed (SMB) technology for biotechnological products Assistants
  Marc Bisschops
12.30 Lunch
13:30 Industrial cases and applications of chromatography: Column design and operation from theory and practice
  Alexander Hanke
14.15 Assignment: chromatography
  Marcel Ottens and Exercise Assistants
15:45 Quality by Design
  Danielle Horneman
17:00 Case study: industrial protein production (IV)
  Marcel Ottens and Exercise Assistants
18:00 End of the day

Thursday 6 July 2023
Theme: Purification & formulation processes
9:00 Bulk crystallization: Unit operation design for the crystallization of small and large biomolecules
  Marcel Ottens
10:15 Assignment: crystallization
  Marcel Ottens and Exercise Assistants
11:15 Industrial crystallization: Real life examples
  Rob Geertman
12.15 Lunch
13:15 Inclusion body processing
  Michel Eppink
14:45 Panel discussion
15:30 Case study: industrial protein production (V)
  Marcel Ottens and Exercise Assistants
19:00 Course dinner

Friday 7 July 2023
Theme: Process development & process integration
9:00 Rational methodology for vaccine purification process development
  Beckley Nfor
10:15 Design of an industrial process for purification of biologicals
  Michel Eppink
11:30 Process integration in industry
  Matthias Wiendahl
12.30 Lunch
13:30 Case study: industrial protein production (VI) Presentations of the three winning teams:
the strategy DSP award ceremony
  Marcel Ottens and Exercise Assistants
14:00 Evaluation of the course
  Marcel Ottens
14:30 Farewell drink


The course will be held at:

Faculty of Applied Sciences (building 58)
Department of Biotechnology
Delft University of Technology
Van der Maasweg 9
2629 HZ Delft
The Netherlands
P +31 (0)15 278 1922
F +31 (0)15 278 2355


The course fee is:

Early Bird €2.750,-*
Regular Fee €3.000,-
Small and medium-sized enterprises (SME/Startups/scaleups) €1.925,-**
Small and medium-sized enterprises (SME/Startups/scaleups) of Biotech Campus Delft €1.375,-**
PhD Students €1.375,-**

*To be eligible for the reduced early bird fee you need to register before 26 April 2023. If this date is exceeded, the regular fee applies.

**A limited number of fellowships is available for PhD students and SME’s (small/medium enterprise). Fellowships will be available on a first-come-first-serve basis. To apply as to one of these fellowships, please include a copy either of your registration as a PhD student from your university or a proof of the SME-status of the company you work at.

The fee includes course materials, lunches and the buffets and the course dinners as indicated on the program. The fee does not cover other meals or lodging. Hotel accommodation can be arranged at your request.

The course fee is preferably paid by bank transfer. Payment by PayPal is possible. TU Delft employees can use their internal (project) code.

Preparatory texts will be sent one month before start of the course and after receipt of the course fee. The complete set of course books will be supplied at the start of the course.

In the event of your cancellation before 10 May 2023, a full refund will be granted. After this date, a 25% fee charge can be made.

Delay of payment past the final deadline as indicated on the invoice may result in cancellation of entry to the course. Re-entry is only possible in case of vacancies and the regular fee will be applied. Payment terms and deadlines will be indicated on the invoice and/or provided in an e-mail after registration, but the course fee should always be paid before the start of the course.

When the number of participants is too low to have a fruitful course, the Institute BioTech Delft will cancel the event no later than six weeks before the start of the course. The course fee will be reimbursed within three weeks after cancellation. In case a speaker will not be able to present his/her lecture, due to unforeseen circumstances, BioTech Delft will arrange an equivalent replacement.


Course board

Luuk van der Wielen – Full professor

Luuk van der Wielen is distinguished Professor for Biobased Economy as well as full professor and group leader Bioprocess Engineering at the Department of Biotechnology of TU Delft. The activities of the section resulted in several spin-off companies. His research interests include thermodynamics for bioprocesses, bioseparation/-conversion technologies, multifunctional bioreactors and miniaturized (‘on-chip’), high throughput technology for rapid process development, as well as analysis and development of large scale and distributed, low carbon biorenewables production systems, and their societal impacts. Since 2004 he is director of BE-BASIC (, the globally operating private-public research organisation for Biobased Sustainable Industrial Chemistry & Energy, which is based in The Netherlands with hubs in South East Asia and Brazil. He was and is coordinator of several leading (inter)national programs on biobased innovation and member of many committees in this field, including on green technology investments. He is one of the initiators of the successful academic program on Life Science & Technology of Leiden University and TU Delft, and director of the postgraduate program Bioprocess Design.

Marcel Ottens

Bioprocess Engineering, Department of Biotechnology, Delft University of Technology, the Netherlands


Marc Bisschops

Pall Europe, Medemblik, the Netherlands

Michel Eppink

Synthon BV, Nijmegen, the Netherlands

Rob Geertman

DSM Fibre Intermediates BV, Geleen, the Netherlands

Danielle Horneman

Bataviabiosciences, Leiden, the Netherlands

Alex Hanke

Novartis Pharma AG, Basel, Switzerland

Beckley Kungah Nfor

Beckley Kungah Nfor finished his BSc in Biochemistry at the University of Buea (Cameroon). After that, he moved to Delft University of Technology, where he completed his MSc, PDEng and PhD degrees, and subsequently did a postdoc. Dr. Kungah Nfor has published several peer-reviewed journal papers and a book chapter on protein purification process development. In his current role as Scientist at Crucell Holland B.V., he focuses on a variety of activities including Early Stage Vaccine Process Development, Technology Transfer and Process Characterization. His main research interests are biopharmaceutical process development, downstream processing, process modeling, quality by design.

Reinoud Noordman

Pentiar X-Flow, Enschede, the Netherlands

Matthias Wiendahl

NOVO Nordisk A/S, Gentofte, Denmark

Eduardo Lau

Janssen Pharmaceutica, Leiden, the Netherlands

Raquel Aires Barros

Universidade Lisboa, Portugal



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    Hall of Fame

    Winners of the Best Downstream Process

    During the course you will work in a team in a case study, designing a downstream process. At the end of the week, the team with the best designed process wins. We proudly present the winners of the last years below:


    Daniel Potthoff and Katya Harkovski


    Diana Godinho and Tuur Vermunt


    Karine Kiragosyan and Bjorn Hendriksen


    Henrik Marke and Christelle Sihabout


    Emmanouela Gratsia and Gerard van Bochove


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