BIOPHAM Mobility

At the beginning of the Master programme, all students will be welcomed in Pisa and will participate to a joint one-week event including a summer school and integration events. During this joint one-week event, all students and teachers will have direct opportunities to meet each other at the very beginning which will reinforce the links. Special events will be organized in order to promote the interactions between students, professors, invited scholars and invited lecturers from industry who will be specially invited to provide courses/lectures in their expertise domains. This event will be the perfect opportunity for students to start building their network.

During the first term in the University of Pisa, all students will have to complete a set of common courses devoted to a broad spectrum of physics, chemistry and materials science topics. It includes quantum physics of matter, solid state physics,  disordered & off-equilibrium systems, mechanical behaviour of materials, polymer science and engineering and transport phenomena in materials.
Depending on their bachelor background and the track they intend to registered to in the following, courses on specific topics will be also proposed as optional courses: polymer science and engineering, transport phenomena in materials, introduction to optical spectroscopy, biofluids and materials interactions, manufacturing of polymers and nanocomposites for biomedical application, rheology, green chemistry for materials and processes and computational materials science.
The goal of this first term is to homogenize and strengthen students background to the level required by the different tracks they are involved in.

During the second term, all students will move to Barcelona. The second term actually marks the first differentiation from teaching general knowledge in the materials science fields towards more specialized courses. It will offer the possibility to students to discover new concepts and approaches topics in a very flexible way based on a selection of optional courses. Students will continue to improve their fundamental skills (physicochemical properties & characterization) and they will start training on drugs (thermodynamics and solid state physics of drugs), biological materials and soft condensed matter (molecular and soft condensed matter, complexity in biological systems), advanced characterization techniques such as offered at synchrotron & neutron sources (large scale facilities) and numerical approaches (computational biophysics, stochastic methods, machine learning with neural networks).

During the third term, students engaged in the “Track 1: soft-matter and biopharmaceuticals” track will move to Katowice to develop their skills on soft-matter (polymers, colloids, gels) as well as biological materials (peptides, proteins, biomaterials) of therapeutical interest and their specificities. In the meantime, students of the “Track 2: condensed-matter and pharmaceuticals” track will go to Lille.
The courses will provide students development skills on the specialized materials science underlying the research pharmaceutical formulation. It will focus on the different materials used in the field of pharmacy, their physical states, their specific modes of preparation and transformation induced by the typical constraints imposed by pharmaceutical industrial processes.
For both tracks, students will get the opportunity to specialize either on numerical techniques applied to drugs (atomistic modelling, mathematical diffusion models for controlled drug delivery) or on dedicated advanced characterization experimental techniques.

The fourth and last term covers the Master thesis of the students. The location where the student will perform her/his thesis is a free choice and can be performed in a research laboratory of a partner University, in an associated academic/industry partner organization or in any other company offering oriented topic for the Master thesis. The students will be strongly encouraged to take advantage of the large network of associated academic and industrial organizations and external associated universities. In any case, an agreement will be signed between the student, the company/laboratory/organization where the work placement takes place and the host University chosen by the student for the fourth term. All defences will be made public and followed by all students (compulsory) thanks to video-conference systems.

The “soft-matter and biopharmaceuticals track” (track 1) (Pisa-Barcelona-Katowice) will provide a training focusing on understanding at the molecular level of the physicochemical and biological properties of small and macromolecules, lipid membrane systems and macromolecular drugs. Biopharmaceuticals are among the most sophisticated medicines and are becoming increasingly prominent in the pharmaceutical industry. Some companies are already spending 40% or more of their R&D budget on biopharmaceuticals and they are expected to dominate product use and sales of the future. However, compared to conventional chemical drugs, therapeutic proteins suffer from intrinsic instability. Changes due to chemical or physical instability can alter protein folding and the protein 3-dimensional structure. It is a major problem because denatured or aggregated protein species will not only be therapeutically inactive, but also may cause unpredictable side effects, such as immunogenicity or toxicity. A strong awareness to attempt for highly stable biopharmaceutical products has thus emerged. Because of their highly limited stability in liquid form, many of these protein-based therapeutics would be unusable within a few days. Solid dosage forms are thus usually preferred. Industries are particularly highly demanding of training with a high fundamental knowledge in biophysics science to face many challenges of protein-based therapeutics because of their intrinsic physical and chemical instability and specific mode of formulation in the solid forms using different techniques of drying (freeze drying, spray drying, supercritical fluid drying). This problematic includes very important fundamental knowledge of materials science such as freezing, thawing, interfacial stress, interaction with specific solvents (water, sugars), mechanism of stabilization (glassy state, water replacement, interfacial adsorption) and know-how of very specific experimental techniques (microcalorimetry, Infra-Red, Raman scattering, Scanning electron micrographs).

The “condensed-matter and pharmaceuticals” (track 2) (Pisa-Barcelona-Lille) will be the counterpart of the previous track and will offer a training very orientated on the heart of “materials science” focusing on the different physical states (perfect and imperfect crystals, nanocrystals, glassy states) of small molecules as well as their surface and interface properties. The development of novel drug products with significant solubility issues have recently focused on alternative solid-state forms such as ill-ordered, disordered or fully amorphous materials and their molecular complexations. These new solid-state forms have attracted a considerable interest from pharmaceutical companies due to superior capabilities but only a few formulations actually led to marketed products because of intrinsic difficulties with these disordered, unstable and complex physical states. Companies are particularly looking for profiles with a strong background on the solid state physical characterization of small molecules (e.g., Dielectric relaxation, Raman and Infra-Red spectroscopies, NMR, X-ray powder diffraction, DSC and TGA thermal analysis), the optimization of performance (e.g., solubility, stability, controlled release) of single component crystalline and amorphous drug substance samples, and on the design by many different techniques (e.g., mechanosynthesis, atomization, solvent evaporation) of multicomponent materials (cocrystalline and coamorphous forms).

For both tracks, two options will be proposed :

• Option A: The “modelling and simulation” option will specifically target students attracted by computer-based simulation and modelling techniques that can be used: i) to process enormous quantity of physical/chemical data to create outcomes that help us in drug development and ii) to characterize interactions of pharmaceutical materials at the molecular scale for studying for example highly complex transformations processes. Nowadays, modelling and simulation have become indispensable in drug development. Data can be leveraged to provide important insights on drugs material properties and predictions in order to enable key drug discovery decisions from early discovery stages. Industries are eager of profiles – which they are particularly lacking – that possess an excellent understanding of theory, principles and aspects of advanced modelling and simulation and in depth hands-on knowledge of state-of-the-art modelling and simulation software.
   
• Option B: The “advanced experimental characterization techniques” option will provide training on the use of large facilities (synchrotron & neutron sources) and advanced spectroscopic techniques to probe structural, microstructural and dynamical properties of pharmaceutical materials. For this purpose, large scale facilities are involved as associated partners in BIOPHAM (see associated partners). Synchrotron light is considered essential in modern pharmaceutical research illustrated by recent reports published by big pharmaceutical companies’ scientists at different larger scale facilities such as ESRF in France or Elettra Synchrotron in Italy (see associated partners). Because synchrotron light possesses brilliance more than a billion times higher than a simple laboratory X-ray source, it offers the possibility to “see” in much more details the material under study. Popular “materials science” techniques for investigating structure in pharmaceutical formulations include X-ray diffraction and crystallography that are able to provide nanoscale structural information, small angle X-ray scattering which can provide information about phase behaviour and microstructure in soft systems (solutions, suspensions, gels and emulsions) or X-ray imaging by tomographic studies that can provide direct complex internal structures in tablets or capsules. Structural information often required to be complemented by dynamical information as obtained by advanced spectroscopic techniques such as broadband dielectric relaxation. It is especially important for partially or completely amorphous materials that are often created during drugs processing and that have become increasingly important in the last decade in the pharmaceutical developments. The use of such complex instruments and analyses of the obtained data requires very specific and rare training in material sciences (crystallography, imaging, data treatment and spectroscopy) very sought by companies in particular to their emerging research fields and their “Quality by Design” approaches.