Title Promoter Affiliations Abstract "Risk assessment as a lever for sustainable procurement" "Karen Van Bastelaere" "Research Centre for Sustainable Organizations" "Within procurement and risk management, various models exist that can be used to assess suppliers and risks, respectively. In part, these have already been adapted to current concerns, including by adding sustainable criteria or quantifying risks in procurement models. Nevertheless, there remains a large gap in the literature regarding risk models that support a sustainable procurement policy in a quantitative way. There is also a need for such models from a practical perspective: previous research shows that only a minority of companies use quantitative measurement systems to perform risk assessment. The goal of this PhD research is first of all to investigate which risks determine a sustainable procurement process and how these risks are perceived by companies. Moreover, a model and accompanying tool will be developed to allow companies to easily perform a quantitative risk assessment to support a sustainable procurement policy. The model and tool make companies more aware of the internal and external risks associated with procurement and support decision-making processes from a sustainability perspective. The project combines quantitative and qualitative research in three main phases. Phase 1 is a descriptive research and exploratory study aimed at defining a framework and possible criteria for a procurement risk assessment model. An in-depth literature review will precede a quantitative study. The research will probe supplier and risk assessment and the tools used at companies, among others. The exact sampling frame will be determined on the basis of expert interviews. In parallel, a meta-analysis will compare the inventoried supplier and risk models. Phase 2 consists of instrumental research to create a model and also user-friendly tool that can be used by enterprises. Here, the Delphi method is used to define the criteria of the model. Via Multiple-criteria decision analysis (MCDA), complex, mutually conflicting criteria will be presented in a structured way. Using an evaluation survey of Flemish companies, both with and without importer experience, the model will be tested and adjusted. The project ends in phase 3 with an evaluative study that, on the basis of case studies, investigates the use of the model as a lever for a sustainable procurement policy. For this purpose, the tool will be adapted to the specific needs of particular companies. The aim is to further refine the tool, but also to investigate how and to what extent these companies use the tool to support a sustainable procurement policy." "Public administration study of innovative contract and cooperation models as opportunities for more sustainability." "Koen Verhoest" "Public Administration & Management" "This project represents a formal research agreement between UA and on the other hand the Flemish Public Service. UA provides the Flemish Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract. The project aims at strengthening the sustainability of government actions and public procurement in the context of the grand societal challenge to make the economy greener and more sustainable. The project analyses how sustainability aims are inserted into innovative public procurement contracts and cooperation models (including public private partnerships PPPs) and how this is actually applied in real-life cooperation. This is studied in a multi-level context of European legislation and policies." "A multifaceted view on market access of biosimilars" "Isabelle Huys" "Clinical Pharmacology and Pharmacotherapy" "This PhD project aims to study multiple aspects of market access of biosimilars in Europe, with the ultimate goal to formulate recommendations supporting a long-term sustainable biologicals market in the presence of biosimilars. Biosimilars contain an active substance that is proven to be similar, in terms of quality, safety and efficacy, to that of an authorized biological product (reference product) after extensive comparability testing. Following expiry of patent protection and other exclusivity rights on the reference product, these rights may not hinder anymore the market entry of the biosimilar. Once on the market, biosimilars will induce competition leading to cost savings and/or increased patient access to treatment. However, variation in uptake of biosimilars between countries and between active substances for which biosimilars are available, might indicate that countries are not able to fully capture the benefits of competition from biosimilars and urges to study market access of biosimilars in a multifaceted way. Part 1 of this PhD project, provides a general introduction to the topic of market access of biosimilars and explains the rationale and specific objectives of this PhD project (Chapter 1).In Part 2, barriers to the market access of biosimilars and general recommendations to overcome these barriers are described. In Chapter 2, six barriers were reported, as identified in 2015: the manufacturing process, the regulatory process, intellectual property rights, lack of incentive, the impossibility of substitution, and the innovator’s reach. For each of these barriers, recommendations were developed to reduce these market access barriers, i.e., i) invest initially in advanced production processes with the help of single-use technology, experience or outsourcing, ii) limit patent litigation, eliminate evergreening benefits, build out further the unitary patent and unified patent litigation system within the EU, iv) create demand-side policies, disseminate objective information, v) change the attitude towards biosimilar switching/substitution, starting with physician and patient education, and vi) differentiate the biosimilar by service offerings, use an appropriate comparator in cost-effectiveness analyses.A description of the players in the biopharmaceutical market and different competitive activities can be found in Part 3. The descriptive analysis in Chapter 3 shows that the top 25 pharmaceutical companies are all engaged in the biopharmaceutical market. A snapshot as of December 2016 shows in which way these companies diversify to strengthen their position in the biopharmaceutical market, i.e., via the development of originator biologicals, investment in biotechnology, development of ‘next-generation’ biologicals, development of biosimilars, investment in emerging countries, and collaboration between companies. The latter has been often adopted as a way to, for example, gain access to regions the company has less experience with.In Chapter 4, we investigate competition strategies related to intellectual property rights by mapping patents and patent applications for originator as well as biosimilar monoclonal antibodies in Europe. Via an analysis of case law, it was investigated to what extent patents for the originator product are a hurdle to biosimilar market entry. In addition to the basic patent and supplementary protection certificate, secondary patents (for example on a new indication, new formulation/administration form, or new dosage regime) can in some cases be a substantial hurdle for biosimilar developers to overcome, either via patent litigation cases or by inventing around the patented invention. As many of the studied cases were won by biosimilar developers, these hurdles seem surmountable, but, nonetheless, can delay market access of the biosimilar and create uncertainty on its launch date. Patent protection on biosimilars mainly pertains to new formulations.Part 4 aims to investigate and describe market entry of biosimilars. In Chapter 5, the current European regulatory framework for biosimilars is discussed, including perspectives on this framework from external stakeholders (i.e., healthcare professionals and patients), and ongoing initiatives and future developments to enhance the efficiency of the regulatory process and evolve towards a multi-stakeholder collaboration. The main challenge will be to educate physicians and other healthcare professionals on the biosimilar development pathway. For this, an active communication strategy is needed targeting physicians.In Chapter 6, we zoom in on price setting of a specific product and report for 30 European countries list prices of originator adalimumab (world’s best selling medicine) before and after loss of exclusivity in October 2018, changes in reimbursement status of adalimumab products following the introduction of biosimilars, and relevant national policy measures. When disclosed by the survey participants, actual prices are presented for originator adalimumab after loss of exclusivity (11 of the 30 countries). List prices and actual prices varied widely between countries and in general decreased after loss of exclusivity. However, in some countries, six months after loss of exclusivity, the list price of originator adalimumab was still the same. A limited number of countries has made changes to the reimbursement status of adalimumab products after the entry of biosimilars. Also, only few countries adopted specific polies and practices for (biosimilar) adalimumab, although more general measures regarding biosimilars might already be implemented.In Chapter 7, we explore methodological issues for economic evaluation of biosimilars in the context of reimbursement of biosimilars. When the reference product is reimbursed, it is not deemed necessary to conduct an economic evaluation, but rather a comparison of prices. If the reference product is not reimbursed for a specific population or indication, or is not the standard of care, a full economic evaluation (e.g. cost-effectiveness, cost-utility or cost-benefit analysis) of the biosimilar versus the standard of care is recommended. Also in case of differences in administration form or adherence, or to take into account value-added services, a full economic evaluation might be needed. As only few national guidelines of HTA bodies and reimbursement agencies address these different cases, we recommend that clear guidance is developed on how to assess the value of a biosimilar. It can be argued that even if an economic evaluation can be useful for a biosimilar, this entails an extra cost and time investment, which might challenge pricing of the biosimilar and early competition.In Part 5, the European biosimilar policy landscape is described, and starts with an overview of biosimilar policies in 24 European countries in Chapter 8. In most countries, specific supply-side policies for biosimilars were in place. However, few countries have adopted demand-side policies to stimulate the use of biosimilars. These policies are mainly limited to educational initiatives for physicians, and entail to a lesser extent incentives for other healthcare professionals.In Chapter 9 and 10, regional market dynamics of originator and biosimilar infliximab (hospital setting) and etanercept (outpatient setting) are presented for the 21 counties of Sweden. Furthermore, it is examined how these market dynamics are influenced by local policy measures and practices, in addition to national policy. Market shares of biosimilar infliximab and etanercept varied widely between the Swedish counties. For infliximab, a simple linear regression analysis for the year 2017 showed that 59% of the variability in biosimilar market shares could be explained by the relative difference in discounted price between biosimilar and originator product. For etanercept, prices are coordinated on a national level and any differences in biosimilar uptake suggest that counties react differently to the estimated limited price difference between biosimilar and originator product. In addition to the influence of the price difference, the presence of key opinion leaders, local guidelines and how savings will be distributed among stakeholders, appeared to play a role in originator/biosimilar market dynamics for both molecules. To facilitate the implementation of policy measures, enabling factors such as a multi-stakeholder approach, an altruistic attitude and good communication between colleagues could be identified.In Chapter 11, we discuss Belgium as an example of a country with low biosimilar uptake. Although achieving high biosimilar market shares is not necessarily a goal in itself, as cost savings in Belgium are also realised by mandatory price reductions on originator medicines, we believe that biosimilars are essential to ensure the long-term sustainability of the off-patent biologicals market. Several ad hoc measures have been adopted to increase competition in the Belgium’s off-patent biologicals market. However, we suggest that all stakeholders develop a long-term coherent, integrated policy framework that is built on the following four pillars: i) the creation of a proactive and transparent climate supporting a level playing field for both biosimilar and reference product, ii) investment in educational activities, including raising awareness of societal responsibility iii) enforcement of the practical implementation of public procurement law, and iv) development of physician incentives.  Finally, in Part 6, we formulate recommendations supporting a long-term sustainable biologicals market in the presence of biosimilars (Chapter 12). The concluding discussion puts forward eight recommendations: i) Develop a coherent policy framework with multi-stakeholder involvement, ii) Reduce hurdles related to patents to ensure timely biosimilar market entry, iii) Establish an active communication strategy on regulatory aspects targeting healthcare professionals and patients, iv) Look at actual prices rather than list prices when studying price effects, v) Implement pricing and procurement systems that stimulate competition, vi) Implement a tailored approach to economic evaluation of biosimilars, vii) Invest in educational activities, and viii) Create demand-side policies.Future research should focus on new players on the market, shifts from biosimilar and reference product to newer innovative therapies, identification of factors affecting competition and sustainability of the market, and physicians’ behaviour in adopting of new medicines." "Labour Law and the global supply chain" "Christina Hiessl" "Faculty of Law and Criminology" "The proposed research explores mechanisms of achieving compliance with core labour standards along the supply chain. The EU’s recent proposal of a Directive on Corporate Sustainability Due Diligence adds to a nascent body of law and policy initiatives aiming to reach out beyond the boundaries of applicability of national or supranational law, by expecting transnationally operating companies to use the economic leverage they have in their business relations for the enforcement of labour standards. The current piecemeal cluster of promising initiatives indicates the need for and potential of an integral approach, which builds on existing mechanisms and integrates them into a transparent framework. To establish a basis for an informed discussion of the way forward, the project takes stock of experience with mechanisms such as the conclusion and enforcement of International Framework Agreements and sectoral multi-stakeholder initiatives, public procurement conditionality, subcontractor liability mechanisms, transparency requirements, taxonomy (labelling) regimes, and the “outsourcing” of enforcement to international bodies such as the ILO’s supervisory organs or unions and civil society on the ground." "Legal analysis of Belgian legislation in order to facilitate the transition to a circular economy in the construction sector" "Bernard VANHEUSDEN" "Centre for Government and Law" "Today we use a so-called linear approach in our production processes (take – make – waste). Significant amounts of waste are being produced each year without ensuring reuse or adequate recycling. Because of these practices, the extraction of (finite) natural resources continues. The construction sector is a strong economic and resource-consuming sector and, therefore, has a certain responsibility in this matter. Various stakeholders from the construction sector are aware of this and are willing to make a change towards a different and more sustainable approach: a circular economy. This is an economy that tries to retain the value of products, materials and natural resources for as long as possible and wants to minimise the production of waste. Within this research, I will conduct an analysis of two legal themes (waste/materials and public procurement) in order to find out if Belgian legislation hinders the transition to a circular economy and how we could solve some of the obstacles we may encounter." "Improving customer-led agri-food innovations: potential of explicit and implicit behavioral measurements" "Joachim Schouteten" "Department of Agricultural Economics" "This research aims to explore innovative approaches for enhancing customer-led agri-food innovations by leveraging explicit and implicit behavioral measurements. We intend to conduct a systematic literature review to assess existing knowledge and identify research gaps. Additionally, we plan to procure advanced equipment for behavioral measurements.Our proposed research will integrate explicit measures, such as surveys and interviews, with implicit measures, including eye-tracking and facial analysis. This holistic approach seeks to provide profound insights into consumer preferences and decision-making processes.By combining a thorough literature review with cutting-edge research equipment, this study holds the potential to advance our comprehension of consumer behavior. Furthermore, it has the capacity to transform the strategies employed by agri-food businesses in innovation, ultimately leading to the development of more sustainable agri-food products." "Differential scanning calorimetry (DSC) to study interactions in complex food systems" "Koen Dewettinck" "Department of Food Technology, Safety and Health, Department of Green Chemistry and Technology" "Food products are structured composites of lipids, proteins and carbohydrates. Understanding the complex interactions between these components and their behavior during processing, storage and consumption, is a prerequisite to design more nutritious, sustainable and tasty foods. To achieve this, differential scanning calorimetry (DSC) is an indispensable tool allowing the study of phase or state transitions involved in food ingredients and end products, including glass transition, melting and crystallization properties, protein denaturation and starch gelatinization. This project intends the procurement of a state of the art DSC with autosampler to replace the current outdated equipment. As DSC is an essential and basic tool within food structure research, the new equipment, showing better resolution and sensitivity, will allow continuation and expansion of the research portfolio in a global context of protein shift and reformulation towards innovative plant-based foods." "Support Centre - Circular Economy" "Centre for Government and Law" "As part of the CE center, UHasselt provides public law expertise. UHasselt will do research on public law related matters of circular economy such as public procurement law, tax law, public contract law etc. CE Center conducts policy-relevant research in the context of the circular economy and brings together researchers from KU Leuven, UGent, UAntwerpen, UHasselt and VITO." "Impact of external factors on band alignment of TMDs with SiO2: WS2 versus WSe2 and MoS2" "Valeri Afanasiev" "Semiconductor Physics" "Over the past 50 years Si based integrated circuits have been downscaling tremendously to create faster logic chips and high-volume memory circuits. Such scaling required significant technological advances and innovative designs. Unfortunately, as transistor channel lengths have been approaching 10 nm, it became clear that such aggressive scaling would not be sustainable for Si based transistors. In looking for solutions one addresses more exotic materials namely two dimensional (2D) crystals, such as graphene and transition metal dichalcogenides (TMDs). These TMD structures are particularly auspicious as all atomic bonds are saturated within a monolayer which consists of a transition metal atoms sandwiched in between two chalcogen atom layers. As a result, in an ideal TMD crystal no dangling bonds are expected to be present at its surfaces or interface with other solids. Therefore, single or few-monolayer TMD films have been suggested as potential semiconductor channel materials enabling further transistor downscaling.A fundamental factor of such 2D based devices that can’t be overlooked are the semiconductor/insulator band offsets, as they control the leakage currents and built-in potentials. The most straightforward way to determine these interface band offsets is by internal photoemission (IPE) of electrons and will be employed here to investigate the band offsets for synthetic MX2 TMD layers with the industry accepted insulator (SiO2) where M=Mo, W and X=S, Se. We shall focus on the WS2/SiO2 interface as it is projected as the most promising candidate for field-effect transistor (FET) applications. The main goal of this dissertation is to trace parameters possibly influencing reproducibility, stability, and variability of the MX2/SiO2 interface band alignment.In this work, a novel technique is introduced to characterize excitonic features of the 2D films using transient photoconductivity observations. An expansion of the technique is developed, that allows for the observation of excitonic features through a semi-transparent top contact layer, allowing for 2D film monitoring upon processing. A demonstration of the film quality assessment after such processing steps or extended storage is given. Furthermore, the transient photoconductivity method can be used to evaluate the built-in potentials at the interfaces of 2D semiconductors. As interface band alignment schemes are procured in this dissertation, an accurate determination of the WS2 band gap is achieved through transient photoconductivity spectroscopy using electric field-dependent measurements.IPE measurements are used to determine the barrier height between the WS2 valence band (VB) top edge position and the SiO2 conduction band (CB) bottom for several WS2 synthesis techniques, this in an attempt to trace parameters causing interface variability. Analysis of WS2/SiO2 interface barriers indicates that the band alignment is not only sensitive to the number of monolayers in the semiconductor film but, also, to the WS2 synthesis technique. In particular, for a certain novel low temperature deposition method it is found over various film depositions that despite similar intrinsic properties of WS2 films are achieved, the band alignment may change up to ≈ 0.5 eV, pointing to a crucial impact of the SiO2 surface or the interlayers present. This kind of ""electrostatic"" instabilities emerges as the major extrinsic factor affecting TMD/SiO2 band alignment. At the same time, for monolayer WS2 films the band offsets with SiO2 are found to be less affected by processing steps compared to the earlier results on MoS2. The resilience against oxidation is found to be highly dependent on the film deposition conditions.Although, WS2 is considered as the most promising candidate to replace Si in FETs WSe2 exhibits a higher electron mobility, yet its band offsets with SiO2 remain unexplored. Compared to WS2, IPE analysis of the WSe2/SiO2 interface reveals a ≈ 0.4 eV upwards shift in energy of the VB with respect to the SiO2 CB.Seed promoters have been found to enhance the MoS2 film quality significantly, however, the effect of introducing additional atomic species into the interface with the underlying oxide are often ignored and its effect on the VB position remains unknown. Therefore, IPE is used to study the effect of seed promoters on the VB position of MoS2 films. These reveal that films grown without seed promoter suffer from lateral non-uniformities in the band offsets with SiO2 and electrostatic potential, related to the film discontinuities. However, despite the fact that closed MoS2 films can be grown with a seed promoter, the latter is not only found to change the band offsets by up to ≈ 0.4 eV but, also, introduce lateral band alignment non-uniformities." "Research at the interface between human genetics and reproduction." "Karen Sermon" "Biology of the Testis, Department of Embryology and Genetics" "Today, numerous mitochondrial and nuclear pathogenic gene defects causing mitochondrial disease have already been identified. More recently, our attention has turned towards protein synthesis in mitochondria. Malformations of cortical development (MCD) represent a major cause of developmental disabilities and severe epilepsy. Polymicrogyria (PMG) is a heterogeneous condition, with respect to both phenotype and genotype. In the first part of the project the genetic basis of PMG is addressed. The second part of the study aims at improving the phenotypic characterization of MCD in order to facilitate further genetic research. The research carried out under Inge Liebaers has traditionally had a strong focus on all aspects of reproductive genetics.. Within reproductive genetics, the genetic causes of male infertility is a first topic of interest. To elucidate genetic causes of male infertility, genes with a testis-specific expression pattern will be examined and the whole genome will be investigated for the presence of deletions/duplications. Treatment of male infertility is a logical complement of the former topic. A specific subpopulation of male infertile patients are survivors of childhood cancers who underwent aggressive treatment including chemo- and radiotherapy and bone marrow transplantation. Studies to investigate the genetic and epigenetic aspects of spermatogonial stem cell (SSC) transplantation as well as cryopreservation and tissue expansion are mandatory before a clinical application becomes feasible. Another route to mature sperm would be by differentiation of human embryonic stem cells (hESC) into spermatozoa. As a way to elucidating the pathways controlling differentiation into SSC, dedifferentiation of SSC into pluripotent cells (PC) will be attempted. Safety of assisted reproductive technology (ART), and more specifically at the level of epigenetics and genomic imprinting, is another firm link between reproduction and genetics. We have developed in-house methods for the analysis of DNA methylation on small samples, typically one embryo. Although the majority of children born after assisted reproductive technology (ART) are healthy, recent years have seen the publication of several papers that report on the association of ART and imprinting disorders. Data obtained will subsequently be linked in an anonymous way to the neonatal data obtained from the follow-up study of IVF/ICSI children. Understanding totipotency at the cellular and molecular level will have a great impact on the knowledge of preimplantation development and may have important implications for the current practice in the IVF lab. Although PGD has been part of everyday clinical routine at UZ Brussel since the mid-nineties, we still aim to improve the technology. The combination of several emerging technologies will be evaluated and clinically implemented. Concurrently, data mining of the past 15 years of clinical PGD, will allow for retrospective analysis of PGD data. Clinical research on children born after different ART techniques was started since the introduction of IVF at the UZ Brussel (1983). In the future, studies on (inherited) male infertility in boys born after ICSI will be performed once they reach 18 years in the next few years and the safety of many new techniques (PGD, cryopreservation and vitrification) will be evaluated through the health of the offspring. Other possible risks of ART techniques for the offspring will be examined on the older children of the cohort. Human embryonic stem cell research (HESC) has been established in our group in 2002 and has already led to interesting results and publications. We have currently derived 26 different HESC lines, of which 16 carry a SGD. The great value of these cells for research into fundamental embryology and the molecular basis of the SGD they carry is beyond doubt. We wish to further expand our possibilities for the procurement of pluripotent cells, such as induced pluripotent cells, from different sources. Preliminary results have shown that our hESCs accumulate different types of chromosomal abnormalities, ranging from the amplification of known ""stemness genes"", ie genes involved in pluripotency, to large deletions and duplications. We will explore the causes of these abnormalities by the study of the gene expression. Differentiation into endodermal and mesodermal derivatives will for a large part be carried out in collaboration with other groups. In our own lab, we will attempt to differentiate hESC into mature lung cells, using a liquid-air interface culture system that we have previously developed. Differentiation in normal hESC will be compared with differentiation in hESC carrying a SGD affecting primarily muscle (DM1, FSHD, DMD) or lung (CF). The CRM vitrification project will encompass three fields of application: embryos, oocytes and in extension, pluripotent cells."