Speaker Faculty 2018

Oral delivery of biologics including therapeutic peptides and proteins as well as DNA/RNA-based drugs is certainly a great challenge. In order to reach the systemic circulation after oral dosing these hydrophilic macromolecular drugs have to overcome various barriers being encountered with the GI-tract. In particular the enzymatic barrier (I) being represented by secreted and membrane bound enzymes cleaving them in inactive fragments, the sulfhydryl barrier (II) causing unintended thiol/disulphide exchange reactions between thiols being present in the GI-tract and peptide/protein drugs, the mucus gel barrier (III) restricting macromolecules from reaching the absorption membrane and the absorption membrane barrier per se (IV) are responsible for a comparatively very low oral bioavailability. In order to overcome these barriers, various technologies were explored. Among them, self-nano- and micro-emulsifying drug delivery systems (SNEDDS and SMEDDS), collectively named as self-emulsifying drug delivery systems (SEDDS) have received considerable attention within recent years. Due to the complexation with lipophilic excipients biologics can be incorporated in the lipophilic phase of SEDDS. Once emulsified in the GI-tract to lipid droplets in the size of 30-200 nm, SEDDS provide a protective effect towards a presystemic metabolism, efficiently permeate the intestinal mucus gel layer in order to reach the absorption membrane and provide permeation enhancing properties. Moreover, as SEDDS can be produced in a very simple and cost effective manner, they might have the potential of game-changing delivery systems for the oral administration of biologics.

Take Home Message:

SEDDS are not carrier systems in that you can simply incorporate your drug gaining a sufficiently high oral bioavailability. The potential of SEDDS lies in the huge flexibility for the design of appropriate formulations fully addressing the peculiar properties of each biologic. Within this development process formulation IP is generated.

A short interview with you

• Tell us a little-known fact about yourself! In parallel to my academic career I run a pharmacy standing behind the counter and selling drugs.
• What do you foresee as being the biggest game changers in your industry over the next 5-10 years? So-called ‘drug delivery platform technologies’ are not anymore the future. In particular for the delivery of biologics the game will change to drug delivery companies providing individual solutions for each of these drugs based on a high expertise in the particular field.
• What advice would you give a younger you? If certain strategies/concepts do not prove to be a success within an expected time period, to be much earlier open for alternatives.
• What are your three biggest challenges on a day-to-day basis? 3x Doing research in parallel to all these teaching and administrate responsibilities
• What has been the proudest moment of your career to date? Realizing that first drugs being based on a technology (thiomer-technology) I have invented and developed over the years are reaching the global pharmaceutical market.

Grégoire joined F.Hoffmann-La Roche (Basel, Switzerland) beginning of 2015 in Pharmaceutical Technical Development Biologics Europe. In his new role as Head of Drug Delivery, Grégoire is responsible for the implementation of advanced drug delivery products in Roche’s development portfolio. He works with sterile products and his current focus areas are within sustained release products for ophthalmology and parenterals, as well as within nanotechnologies for targeted drug delivery. Before joining Roche, Grégoire worked in several positions in Pharmaceutical Drug Development at Ferring Pharmaceuticals A/S (Copenhagen, Denmark). In his last position, he established and led a successful early stage development group, having CMC responsibility over a diversified portfolio of peptide and biological drugs, and he led also the company’s drug delivery innovation in the areas of sustained parenteral delivery, enhanced (non-parenteral) peptide delivery and long acting formulations of proteins. Grégoire is educated in Chemical Engineering from the Institut National des Sciences Appliquées (INSA) in Rouen, France. He specialized in polymers for therapeutic applications with a doctorate at the University of Montpellier under the supervision of Prof. Michel Vert. After a few years as Head of Polymer Development with Phusis Matériaux Biorésorbables, he moved on to the University of Geneva in Switzerland, working on sustained release formulations of a proprietary peptide drug for prostate cancer, in the group of Prof. Robert Gurny. During his career, Grégoire co-supervised several PhDs and Master students, participated to two EU-funded consortium projects (Brite Euram and FP7), and is the author or co-author of ca. 20 scientific publications and 6 patent families.

ABSTRACT:

The presentation is illustrating some of the challenges with the pharmaceutical development of products based on advanced drug delivery principles. The first example is taken from the field of injectables, show casing the switch from intravenous infusion to subcutaneous injection of biologics that was successfully applied to several Roche products. This switch required the development of a high concentration formulation combined with a co-formulation development together with a novel excipient enabling subcutaneous injection of large volumes. The second example is dealing with one route of localized drug delivery, namely the ocular route, and more specifically current approaches for long acting ocular delivery of biologic drugs. Here again, innovative technologies are facing the reality check of pharmaceutical development, but are nevertheless progressing in the clinics, showing big promise of patient treatment improvement.

A short interview with you

• Tell us a little-known fact about yourself! I am originating from a wine maker family in Alsace, Ribeauvillé
• What do you foresee as being the biggest game changers in your industry over the next 5-10 years? Advanced Drug delivery systems to enable more efficient and safer treatment for patients
• What advice would you give a younger you? Medical research needs talented young people able to flexibly adapt to an incredibly fast changing environment
• What are your three biggest challenges on a day-to-day basis? To catch up with knowledge available in open world. To accelerate development timelines. To anticipate the future.
• What has been the proudest moment of your career to date?Being part of the core team obtaining global approval in US and EU of Firmagon a self-depoting peptidic GnRH antagonist against prostate cancer

Nikki possesses 23 years’ experience in the pharmaceutical industry and has previously held technical leadership positions in Quadrant Healthcare, Quadrant Drug Delivery and Elan where she was responsible for the development, transfer and scale up of both early phase and late phase spray-dried inhaled and topical products intended for both European and U.S. markets. In her previous position as a Project Director at Vectura, she led the early phase product development for two inhaled, orphan indication products and the late stage development for a novel sterile topical product. Nikki’s responsibilities at Quotient Sciences involve building the global formulation and manufacturing services business.

Christian Lotz studied Physical Chemistry at the University of Bochum and did his doctorate in Physical Chemistry at the University of Essen. He started his Industry career at Lipoid GmbH, a GMP manufacturer of parenteral grade phospholipids, in the sales department with technical and regulatory support functions. Since April 2015 Christian is working as BD Director EMEA at Pfanstiehl, world’s leading manufacturer of low endotoxin and high purity GMP parenteral grade carbohydrate based excipients, providing commercial and technical support to the EU customer base. Christian has 15 years of experience in GMP relevant sourcing and marketing activities of pharmaceutical raw materials.

Olaf Queckenberg studied pharmacy at the Universities of Berlin, Düsseldorf and Freiburg and did his doctorate at the chair of pharmaceutical chemistry of the Freiburg University. From 1994-1999 he was head of analytical development laboratories at Bayer in Leverkusen, Germany, and West Haven, USA. Since 1999 he has been the responsible manager for analytical development at Bayer Healthcare and since 2011 is the head of global pharmaceutical and chemical development at Bayer Pharmaceuticals Division

I graduated from Southampton University with a Masters of Chemistry degree in the summer of 1998 and started working for Zeneca a couple of months later. I have spent the last 20 years working as an analytical chemist in pharmaceutical development at AstraZeneca in Macclesfield, UK. I specialized as an expert in Electron Paramagnetic Resonance spectroscopy and more recently have spent the last 5 years focusing in Predictive Stability, as an Associate Principal Scientist. I am a member of the IQ Risk-Based Predictive Stability Working Group and became a Charter Chemist with the RSC in 2014.

Prof. Dr. Sven Stegemann is director, pharmaceutical business development at Capsugel, and professor of patient centric drug design and manufacturing at the Graz University of Technology, Austria. Over the course of his 20-year career at Capsugel, Dr. Stegemann has worked as an advisor to major pharmaceutical companies on ways to improve the design, development and manufacture of pharmaceutical products so they better address the individual needs of patients. In his academic role, Dr. Stegemann’s focuses his research on the rational development of patient centric drug products and their associated manufacturing technologies, as well as education and training of students and young scientists. Dr. Stegemann is the founder and chair of the AAPS Focus Group on Patient-Centric Drug Development, Product Design, and Manufacturing as well as the founder and President of the Geriatric Medicine Society.

Assistant Professor at Graz University of Technology, Austria and Principal Scientist / Department Head, Advanced Products and Delivery at Research Center Pharmaceutical Engineering (RCPE), Graz, Austria. Amrit is trained in pharmaceutics, and has a broad interest in physical chemistry of formulations and pharmaceutical material engineering. He has long standing activities and an interest in screening, engineering, stabilization and characterization of pharmaceutical solids intended for oral and inhalation routes. His current work also involves predictive knowledge/model development for physical and chemical stability of pharmaceutical solids utilizing material science principles. Recently, he is working towards advancing the predictive knowledge of in vitro biopharmaceutics methodologies via elucidation of multi-factorial physical and chemical process governing drug dissolution and release from conventional to advanced solid dosage forms.

Mike has over 30 years of experience in the medical device industry in a broad variety of technical and clinical areas. He is the founder of five medical device companies and holds over 100 issued and pending US patents. He earned a BS in Physics and a Master of Science in Mechanical Engineering from the University of Michigan.

Jean-René Authelin has an Engineer degree in chemical Engineering from ENSIC (Nancy France), and a PhD from The Institut National Polytechnique de Lorraine (France). He joined Rhone Poulenc in 1988 as a Chemical Engineer. In the 90’s he founded the Physical Quality function, dedicated to the API crystallization, drying, polymorphism where he was the Global head in Rhone Poulenc Rorer, Aventis and finally Sanofi . In 1988, JR Authelin was nominated Global Head of Pharmaceutical Engineering. Domains of interest of JRA include: thermodynamics of hydrates, drug polymorphism, amorphous solids physics, drug stability, crystallization, nanoparticles engineering and processing, drying , milling; spray drying, fluid bed granulation, roller compaction, freeze drying. JR Authelin cooperated with very famous scientists like Prof J.Villermaux, P de Gennes (Nobel price of Physics 1991). Jean René Authelin is the author or co-author of 14 publications or book chapters and the co-inventor of 9 patents

Dr. Kristof Kimpe obtained a master degree in chemistry at the university of Leuven in 1999 and received his Ph.D. in chemistry in 2003 at the same university. He joined Janssen Pharmaceutica in 2005 and assumed global, end-to-end responsibility for excipients. In 2016 Dr. Kimpe joined the preformulation group of the pharmaceutical sciences department, supporting drug product development all the way from pre-clinical to commercial formulations.

Márcio Temtem joined the Hovione in 2008 and has been since involved in the development of the Particle Design and Drug Product Business of the company. In the role of a scientist, group Leader or manager, Marciohas been involved in the development of multiple commercial and latest age programs in the field of solubility enhancement, particularly in the area of amorphous solid dispersions by spray drying, taste masking by spray congealing, microfluidization assisted processes and jetmilling.

Marcio is currently Associate Director for Drug Product Development at Hovione leading the R&D efforts in the field of particle engineering, oral solids dosage forms and inhalation.

Márcio is a PhD in Chemical Engineering with several papers and patents published in topics such as Green Chemistry, Controlled Release, Inhalation, Drug Product, Particle Engineering and Solubility enhancement.

Dr Bastiaan Dickhoff joined the T&I department team at DFE Pharma in 2014 in the capacity of Application Specialist OSD. Bastiaan has been working on assisting in application development of excipients in area of Oral Solid Dose Forms based upon fundamental knowledge of DFE Pharma’s excipients and advances in powder technology. In addition, he is from a Technology and Innovation point of view responsible for the outcome of external collaborations. Prior to working at DFE Pharma Bastiaan held two (2) roles concerning the effect of powders in food and pharma at RSSL (which is part for Mondelez International (UK)) and prior to that Bastiaan has worked between 2005-2012 for GlaxoSmithKline (UK) in various roles.

Bastiaan holds a PhD from the department Pharmaceutical Technology and Biopharmacy at Groningen University, The Netherlands where he specialized in the relationship between the role of lactose (excipient) and API for inhalation purposes.

Mechanic and Automation Bachelor degree in Rennes University, France.

25 years in BD Medical Pharmaceutical System.

I’m engineering project manager for manufacturing process industrialization of glass prefilable syringes for the pharmaceutical industry.

After spending more than 2 decades in several posts in BDM-PS Engineering, R&D and manufacturing department -where I accumulated skills and recognized expertize on the full glass syringes process until Sterilization-, I decided 2 years ago to go back to the sterilization world.

Today I’m leading the WW engineering sterilization roadmap for BD Medical Pharmaceutical system to support capacity requirement, to harmonize practices and processes, to innovate, and to conduct and/or support continuous improvement initiatives.

Bio coming soon

Chemist by education; since 1992 in the pharmaceutical industry; 10 years in pharmaceutical industry in development; 10 years in Biotec (development, production, quality); since 2011 working for Losan Pharma GmbH; responsible for the strategic development and new development platforms in the drug delivery formulation and application field

Sofiya Yashchuk recently joined Roquette as Technical Applications Specialist within Roquette’s Customer Technical Services function. In her role, Sofiya supports BioPharmaceutical suite of ingredients & solutions Roquette brings to customers for use in upstream/downstream bioprocessing, and formulation of biopharmaceuticals. Roquette has a well-established history in naturally derived carbohydrates, polyols, and cyclodextrins; Sofiya supports technical developments of these existing tools in biopharma space, and drives the development of novel solutions to meet the challenges and rigor of biologic-medicines production.

Previous to joining Roquette, Sofiya worked for BASF (USA) in several divisions and functions, including her contribution as Business Development Manager for BASF Pharma Ingredients & Services, where she also focused on delivery and development of solutions for the BioPharmaceutical segment. Sofiya holds a Bachelor's Degree in Biochemistry from the University of Illinois and a PhD in Organic Medicinal Chemistry from Purdue University.

Kaspar van den Dries, MSc, PhD. Dr. van den Dries leads the European R&D team in the development of innovative softgel formulations, processes and technologies. He is an expert in the formulation of poorly soluble compounds and self-emulsifying drug delivery systems with experience spanning the entire solid dosage form development cycle.