Speakers 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

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