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Team

Prof. Dr. Jan Verwaeren

PRINCIPAL INVESTIGATOR

Ghent University
Faculty of Bioscience Engineering
Department of Data Analysis and Mathematical Modelling
Research unit Knowledge-based Systems (KERMIT)
Campus Coupure
Coupure Links 653
B-9000 Gent, Belgium

Jan.Verwaeren@UGent.be

+32 9 264 59 33

In 2018, Jan Verwaeren became associate professor at Ghent University and member of the research unit on Knowledge-based systems (KERMIT, https://kermit.ugent.be/). As a computer scientist, his research interests lies on the crossroads between machine learning, mathematical optimization and image processing. His expertise include methodological and algorithmic development as well as applied research in these areas.

From a methodological point of view, he likes to combine novel insights from the fields of convex and discrete optimization to develop new data analysis strategies for solving predictive modelling, data-reduction and image processing problems. From an application point of view, through collaborations with research units and companies in pharmaceutical engineering, he is currently active in model driven experimental design (active learning) for pharmaceutical product formulation and model-driven predictive maintenance in pharmaceutical production facilities. In the (broader) field of applied biological sciences, he works on projects related to the use of image processing techniques for plant phenotyping, food processing and precision livestock farming.

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Research groups

BIOMATH

Field of Expertise:
Mathematical Modelling

At BIOMATH, we develop and apply mathematical models and methodologies for the analysis and optimization of (bio)processes. The primary focus is on mechanistic models used to support a variety of priority sectors such as pharmaceutical manufacturing technology.

During the last decade, the focus of the group shifted towards a triangle of modelling frameworks, subsequently extending the conventional bio-kinetic models with Computational Fluid Dynamics (CFD) and Population Balance Models (PBM).

  • CFD extends the level of spatial description of reactor systems and was felt as a need since systemic models, such as tanks-in-series approach, became limiting.
  • PBM was a logical addition since this was the topic of Prof. Nopens’ PhD dissertation. This framework allows to model the dynamics of distributed properties of a population of individuals.

Also, combinations of the frameworks can be used to answer complex problems. In that sense, one of the current strategies of BIOMATH is the development and experimental validation of complex models for process understanding. Such a detailed modeling step can be followed by a model reduction step to create simplified models. In the sense that they are mathematically and computationally easier to solve, more accurate, require less calibration and, therefore, have a higher predictive power as compared to lumped process models. BIOMATH has consequently gained extensive expertise in the fields of computational fluid dynamics, population balance modelling and bio-kinetics.

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Research groups

DySC

Field of Expertise:
Modelling, process control, identification, multi-objective process optimization, multivariable control

The Dynamical Systems and Control (DySC) group has research expertise on modelling and control of dynamical systems in several application fields from biomedical to industrial processes.

In the last years the group of Prof. Ionescu has focused on the application of fractional order control as an intermediate control strategy for industry and manufacturing processes, between basic control (such as PID type) and advanced control (such as MPC). Part of this scope is the industrial relevant implementations of MPC and multi-objective optimization algorithms as a function of changing operating context.

Furthermore, there is an ongoing ERC Consolidator grant focusing on the use of computer based constrained optimization of multi-drug infusion rates for anesthesia with strong effects on hemodynamics.

As current topics, the DySC group focusses on modelling and control of dynamical systems with application fields in:

  • Biomedical
  • Chemical
  • Pharmaceutical
  • Mechanical
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Research groups

Epidemiology of Chronic Diseases

Field of Expertise:
Burden of disease, patient-reported health outcomes, health economic techniques

The Epidemiology of Chronic Diseases Research Unit conducts several research projects relating to disease prevention and burden including risk factors epidemiology, lifestyle changes, risk management, physical activity at work and psychosocial risk factors.

The Unit is in close collaboration with the Belgian institute for health Sciensano (Brussels), the National Research Centre for the Working Environment Copenhagen, Jožef Stefan Institute Ljubljana, Imperial College London, Karolinska Institute Stockholm and University of Galway, with whom it shares several projects on the epidemiology and prevention of major health problems in developed and developing countries.

Within the faculty of Medicine and Health sciences, the department of Public Health and Primary Care is internationally renowned for its research in health economics and epidemiology. The research of Prof. Delphine De Smedt, associate Professor, is mainly focused on the burden of disease, patient-reported health outcomes and health economic techniques. She has experience in developing health economics models in different chronic disease areas.

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Research groups

INCAT

Field of Expertise:
Heterogeneous catalysis, reaction engineering, adsorption technology, thermodynamics, separation train design, applied multidimensional chromatography

The Industrial Catalysis and Adsorption Technology research group (INCAT) is part of the Materials, Textiles, and Chemical Engineering department (MaTCh, EA11) within the Faculty of Engineering and Architecture at Ghent University. INCAT primarily focuses on the development of catalysts and adsorbents, with a strong emphasis on renewable resources and environmental management. A major objective is the catalytic conversion of biomass-derived streams, encompassing their upgrading and separation into valuable chemicals. INCAT’s research endeavours have a practical, application-oriented approach, addressing the specific needs of industries. To achieve this, the group actively collaborates with consortiums and industrial partners, including small and medium-sized companies in the broader chemical industry.

INCAT encompasses a diverse range of expertise across various chemical engineering domains. INCAT specializes in heterogeneous catalysis and reaction engineering, involving the synthesis, characterization, and performance testing of catalysts, as well as developing intrinsic kinetic and industrial reactor models to optimize reaction conditions and design efficient catalysts.

The research group also has extensive knowledge in adsorption technologies and focusses on developing methods to recover high-value components from waste streams that are present in low concentrations. By designing and implementing efficient adsorbents and recovery techniques, INCAT contributes to sustainable resource management.

Thermodynamics and separation train design also form an essential part of INCAT’s expertise, as the group delves into the thermodynamics of molecules containing multiple functionalities and/or heteroatoms, creating thermodynamic models that aid in the design of effective separation trains for various chemical processes.

Additionally, INCAT explores the development of multidimensional chromatographic analysis techniques, encompassing both liquid and gas phases to enable the analysis of complex mixtures, such as non-volatile aromatics, providing valuable insights for various applications.

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Research groups

LCT

Field of Expertise:
Chemical Technology

The Laboratory for Chemical Technology (LCT) integrates chemical science and engineering in its research on catalysis, polymerization, kinetics, reactor design and process design. LCT is part of the Department of Materials, Textiles and Chemical Engineering within the Faculty of Engineering and Architecture at Ghent University in Belgium. LCT aims at research excellence and bottom-up innovation in the framework of technological, industrial, and societal challenges.

The research within LCT is based around six themes:

  • Polymer design: This research theme specifically aims at the design of new polymeric materials up to industrial scale, considering advanced multi-scale computational tools. Our goal is to take control over the entire microstructure of individual polymer chains, taking into account economic and environmental constraints.
  • Catalyst design: This research theme aims at the full exploitation of existing reactor technologies and the development of new reactor technologies. Main focus is on the study of the delicate interplay between reaction kinetics and mass, energy and momentum exchange phenomena.
  • Reactor engineering: This research theme aims at the full exploitation of existing reactor technologies and the development of new reactor technologies. Main focus is on the study of the delicate interplay between reaction kinetics and mass, energy and momentum exchange phenomena. Given the large scale of most commercial chemical processes, the smallest improvement in reactor design has a huge impact on the use of resources and the operating costs.
  • Circular process design: Today we must consider the whole lifecycle of our resources. Fundamental changes are needed in all these parts of the process industry, in particular in the design of these processes where exergy analysis, resource efficiency and life cycle analysis are fed by fundamental process simulation data that account accurately for the important chemical and physical phenomena on different scales. 
  • Low carbon technology: The transition from a raw material base towards an almost carbon neutral economy is one of the biggest challenges. Catalysis is a key enabling factor to allow the development of new sustainable processes and technologies and thus plays a critical role to realize transition from a linear to a circular economy. Consequently, the development of catalysts and related catalytic technologies for the use of CO2 to produce chemicals and fuels, and renewable energy in chemical production is becoming a key area.
  • Renewable chemicals and technology: In this research theme, emphasis is on the development of fundamental so-called microkinetic models together with dedicated ab initio calculations and elaborate catalyst characterization to enable this extension. The individual phenomena investigated range from the chemical kinetics, over mass and heat transport phenomena and phase/thermodynamic effects, to non-ideal reactor hydrodynamics.
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Research groups

Laboratory of General Biochemistry and Physical Pharmacy

Field of Expertise:
Nanomedicines, biopharmacy

Currently the Laboratory of General Biochemistry & Physical Pharmacy houses 4 closely collaborating research groups: the Biophotonic Research Group, the Ocular Delivery Group, the Lung Delivery Group and the Vaccine Delivery Group. The global research focus of our teams is on the delivery of bio-therapeutics, especially nucleic acids. Our teams offer a multifaceted portfolio of competencies including pharmacology, material knowledge and expertise in drug delivery, nanotechnology, cell biology, immunology, biophysics, optics and bio-photonics.

  • Biophotonics Research Group: Research of this team is as aimed at the development of biophotonics-based technologies to (i) study the biophysical behavior of nanomedicines in cells and tissues and (ii) enable more efficient drug delivery. With regard to the former, the Biophotonics Research Team has specialized in the development of advanced light microscopy methods and their application to study the interaction of nanomedicines with biological barriers.
  • Ocular Delivery Group: This group is highly experienced in developing (and using) in vitro, ex vivo and in vivo models for the evaluation of non-viral nucleic acid delivery to the retina. This team recently developed an ex vivo retinal explant from bovine eyes which keeps the vitreous and inner limiting membrane (ILM) intact during dissection. This allows to evaluate the potential of intravitreally injected nanoparticles to deliver therapeutics to the retina.
  • Lung Delivery Group: The Lung Delivery Group mainly focuses on exploring novel ‘bio-inspired’ approaches for the delivery of nucleic acids. A major aim of this team is to develop innovative strategies to stimulate cytosolic delivery of nucleic acids in lung-related target cells for the treatment of pulmonary pathologies with a clear unmet medical need, including obstructive lung diseases and respiratory infections. To reach this goal, the team focuses on (i) exploiting endogenous materials for drug delivery, such as pulmonary surfactant, (ii) repurposing of small molecular drugs as adjuvants to promote nucleic acid delivery and (iii) improving nanomedicine design for in vivo use.
  • Vaccine Delivery Group: Research projects of the Vaccine Delivery Group are situated at the interface of drug delivery and immunology. As such, we explore the potential of nanotechnology or physical approaches (ultrasound) to manipulate the immune system.
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Research groups

LPPAT

Field of Expertise:
Process Analytical Technology

The Laboratory of Pharmaceutical Process Analytical Technology (LPPAT) focuses on the implementation of PAT systems in innovative pharmaceutical production processes and therefore has always worked in close collaboration with the Laboratory of Pharmaceutical Technology of Prof. Dr. C. Vervaet and is part of the QbD and PAT Sciences Network. 

Manufacturing processes of interest:

  • Freeze-drying
  • Continuous wet granulation
  • Production of solid oral dosage forms
  • Continuous melt granulation

Implementation of PAT systems:

  • The development and implementation of process analyzers in the process stream allowing real-time collection of critical process and (intermediate) product information.
  • Data-analysis methods (chemometrics) allowing to extract useful information from the large datasets that process analyzers supply. Process analyzers are only valuable if they provide the desired information with sufficient accuracy. Being able to build accurate and robust models to reliably translate the data (e.g., obtained spectra) into process or product knowledge is crucial.
  • Design of Experiments (DoE) to maximize the information content from experimental series while keeping the number of experiments low. As the process (step) endpoints and the intermediate or end product properties (e.g., product solid state, chemical properties, physical properties,…) are influenced by numerous process and formulation variables, appropriate experimental design approaches must be applied to find out which variables and variable interactions significantly influence processes and product properties.
  • Statistical process control and visualization: a final aim of implementing PAT systems in pharmaceutical production processes is complete process control. Based on process knowledge and process models, the information obtained in real-time should be used for guiding the process to its desired state, possibly allowing real-time release. Early warnings should be given when a process is moving into an unwanted direction and the process models should allow to determine how process settings must be adapted by operators to lead the process to its desired state, thereby reducing batch rejection.
  • Mechanistic modelling: empirical modelling is based on historical data and as such they are of limited use in new applications outside the experimental space studied. Apart from cause-and-effect between variables, not much else is required in terms of process knowledge. Mechanistic modelling is based on the fundamental understanding of the underlying physics and chemistry governing the behaviour of the process. Hence, mechanistic modelling does not require much data for model development, and hence is not subject to the idiosyncrasies in data. Mechanistic modelling forces to fundamentally and completely understand processes. The different steps of mechanistic modelling are mentioned in appendix. This new approach of modelling of pharmaceutical processes should allow making useful process simulations and process predictions.
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Research groups

Laboratory of Pharmaceutical Technology

Field of Expertise:
Pharmaceutical technology

The research at the Laboratory of Pharmaceutical Technology (Ghent University) focuses on the development of innovative drug dosage forms (mainly solid dosage forms) for human application as well as for veterinary use. These dosage forms are based on pharmaceutical accepted excipients used as such or as mixtures to impart specific drug release properties (immediate, controlled or sustained release) to the formulation. The lab has a strong research focus on continuous manufacturing techniques.

The projects at the Laboratory of Pharmaceutical Technology are focused on the following topics:

  • Granulation: Current research mainly focusses on process and formulation development for twin screw wet and melt granulation as well as their downstream processes. Therefore, evaluating the interplay between raw material properties and process settings is of high interest. This approach is used to (i) derive preferred excipients platforms for novel APIs, (ii), evaluate the impact of batch-to-batch variability and (iii) evaluate the applicability of botch conventional and non-conventional excipients for continuous processing.
  • Tabletting: Ongoing work investigates the influence of raw material and blend properties on the die-filling and tabletability during continuous manufacturing. Residence time distributions in the feedframe and influence of different process parameters are being studied. In addition, the influence of feeding and blending during continuous direct compression on the tablet content uniformity is evaluated.
  • Compaction simulation: Currently, our team is working on the evaluation of the external lubrication system on the compaction simulator (Styl’One Evolution). In addition, the correlation between the tableting process and tablet quality of tablets produced on the Styl’One Evolution tableting instrument and Modul™ P rotary tablet press is studied.
  • Hot-melt extrusion and 3D-printing: Hot melt extrusion is used for designing sustained release dosage forms using conventional and non-conventional polymeric materials for controlled drug release. On the other hand, the extrusion process is used to enhance the bioavailability of poorly soluble drugs by preparing molecular dispersions for immediate release dosage forms. The development of personalized 3D dosage forms with versatile release profiles is also one of our research interests. Recently, FDM 3D printing was used as an alternative HME downstream processing technique to produce personalised medicines for the manufacturing of high drug loaded dosage forms, hence offering a lot of formulation freedom for the on-demand production of personalized dosage forms at the point-of-care.
  • Spray-drying: Research on the spray dryers is focussed on formulation of particles for dry powder inhalation, co-processing to obtain particles with the desired properties (e.g. improved compressibility, flowability) and creation of micro-particles for oral antigen delivery.
  • Freeze-drying: Our lab developed a continuous freeze-drying process in collaboration with the Laboratory of Pharmaceutical Process Analytical Technology. This continuous freeze-drying concept is based on spinning the vials during freezing (I.e. spin-freezing) and on non-contact energy transfer via infrared radiation during drying. This improves process efficiency and product uniformity compared to conventional batch drying. Our research focus is development of a formulation strategy and optimisation of the models used in the different steps of continuous freeze-drying.
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Research groups

Supramolecular Chemistry Group

Field of Expertise:
Polymer chemistry and polymer materials

The research of the Supramolecular Chemistry Group (Ghent University) focuses on the molecular design of polymer materials for a broad range of applications, including drug delivery, biomaterials and excipients. The group has a strong expertise in the synthesis of defined (functional) polymer structures with a special emphasis on poly(2-oxazoline)s, responsive polymers and supramolecular materials.

Some illustrative examples of relevant projects are listed below:

  • Poly(2-oxazoline) matrix excipients for oral dosage forms enabling high drug loading (up to 70%-80) amorphous solid dispersions of poorly water-soluble drugs, such as flubendazole, mebendazole and fenofibrate
  • Poly(2-oxazoline) matrix excipients for oral dosage forms enabling high drug loading (up to 70%) sustained release formulations of drugs with good water solubility, such as metoprolol tartrate and metformin
  • Cationic polymers for transfection of pDNA, siRNA, mRNA and saRNA enabling better in vitro transfection than lipofectamine and similar in vivo transfection as lipid nanoparticles
  • Polymer-drug conjugates to reduce systemic toxicity and enhance blood circulation time, possibly in combination with targeting ligands, including antibody-drug conjugates
  • Polymer-protein conjugates to enhance blood circulation time and enhance protein stability
  • Responsive polymers that are insoluble in the blood stream but rapidly solubilize upon cell internalization, through either protonation or degradation of side chains under mild acidic conditions
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Research groups

SynBioC

Field of Expertise:
(Bio) Organic Chemistry

The Synthesis, Bioresources and Bioorganic Chemistry (SynBioC) Research Group is active in the broad field of organic synthesis with projects ranging from the synthesis of new bioactive compounds for applications in the medicinal and the agrochemical field, the isolation and study of natural products, the use and chemical modification of renewable resources, to the implementation of green chemistry, microreactor technology and photo chemistry.

Within the framework of organic and bioorganic chemistry, the following research lines are elaborated:

  • The chemistry of small-ring azaheterocycles: This research involves the study of regio- and stereoselective ring transformations of constrained (phosphonylated) azaheterocycles such as aziridines, azetidines and beta-lactams. Next to the fundamental aspect of designing and evaluating new synthetic methods, the application of these techniques is also employed for the construction of a broad variety of heterocyclic target compounds with biological interest (diversity-oriented approach).
  • Synthesis of bioactive substances: Several projects are focused on the synthesis of specific classes of natural product analogues (e.g. curcuminoids, quorum sensing signaling compounds) and other new compounds associated with certain biological activities (target-directed approach). Examples include the synthesis of anticancer agents, antibiotics, antimalarials, analgetics, HDAC-inhibitors, crop protection products,…
  • Green chemistry and renewable resources: Renewable chemicals and materials are currently a hot topic in research and industry. The depletion of fossil resources and the exhaust of greenhouse gases force us to think about alternative sources for the chemical industry and the energy sector..Our research group focuses on the modification of non-fossil resources towards renewable chemicals, such as the modicification of biopolymers (inulin, chitosan), the use of 10-undecenoic acid (derived from castor oil) and the production of biofuels and renewable fuel additives.
  • Microreactor technology: Microreactor technology (MRT) provides a number of specific advantages compared to batch processes: it is often more selective and efficient, has a better mass and heat transfer capacity, consumes often less reagents and solvents, has good safety features and allows to work with very reactive and/or toxic reagents. The SynBioC research group is active in the application of microreactor technology for multicomponent reactions, reactions using dangerous reagents, fotochemical and low temperature reactions.

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News

PHD position open in pharmaceutical technology!

Fascinated by pharmaceutical process development and how novel drug manufacturing techniques contribute to that? Eager to pursue a PhD in Pharmaceutical Sciences on the industrial implementation of continuous tablet manufacturing via direct compression?

This could be your opportunity! A collaboration between Ghent University CESPE and Johnson and Johnson Belgium!

More information on the topic and how to apply on the UGent Job portal!

Short project description

The pharmaceutical industry is switching from batch-wise to continuous manufacturing of tablets. The aim of current project is to address crucial gaps of knowledge for industrial implementation of continuous tablet manufacturing via direct compression.

During drug product development limited amounts of new chemical entities are available to investigate the effect of formulation and process variables on the final drug product. The first aim is therefore to develop a strategy for identification of a surrogate component, i.e. a component with similar characteristics as the new chemical entity, to use during early process and formulation development trials. Furthermore, continuous feeding of very cohesive raw materials is often challenging and affects further downstream processing. Therefore, various formulation strategies to overcome feeding issues of very cohesive raw materials in function of process parameters will be developed. Finally, a control strategy based on residence time distributions is of utmost importance to ensure the final product quality and traceability along the manufacturing line. Therefore, the critical formulation and process parameters affecting residence time distributions on a continuous direct compression line will be investigated and predictive models will be built for each unit operation and for the integrated line.

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News

HANDS-ON WORKSHOP ON BATCH VERSUS CONTINUOUS PHARMACEUTICAL FREEZE-DRYING, OCTOBER 16-18, GHENT

Interested in the capabilities of continuous freeze-drying? What is the impact on stability, supply chain, manufacturing operations, quality control, etc.?

Subscribe to the hands-on workshop on batch versus continuous freeze-drying of pharmaceuticals!

  • Demonstration of continuous freeze-drying prototypeF
  • Formulation characterization for batch and continuous freeze-drying hands-on training
  • DEMO PAT for continuous freeze-drying
  • Dynamic design space determination
  • Execution of batch and continuous freeze-drying processes for selected formulations
  • Evaluation performed batch and continuous freeze drying runs
  • Determination CQAs freeze-dried products: batch versus continuous
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News

CESPE PRESENTS AT KNOWLEDGE FOR GROWTH 2018

CESPE will present to you at Knowledge for Growth 2018 this week Thursday 17th in Ghent #KfG2018! Visit us at exhibition booth 75, first floor of TTO Flanders Ghent University Tech Transfer to get to know more about the Centre of Excellence in Sustainable Pharmaceutical Engineering. #KfG2018 with flanders.bio. https://www.knowledgeforgrowth.be/