MIBio 2017 Programme - click titles for abstracts
08:00 Registration opens
09:00 Opening remarks
09:15 The key roles of formulation and orthogonal analytical methods in the
success of biopharmaceuticals
Prof. Tudor Arvinte | Professor University of Geneva, Chairman & CEO,
Therapeomic Inc, Switzerland
09:45 Formulation development challenges of bi-specific antibodies
Stephanie Davies | MedImmune, UK
10:15 Speed Networking
11:15 Stability challenges with ADCs
Adithya Balasubramanian | Lead Scientist, Lonza Drug Product Services,
11:45 Development of parenteral multidose products – the challenge of
Helen Sjögren | Principal Scientist, Ferring, Denmark
12:15 Lunch Break, Exhibition and Posters
13:30 Discussion panel - Formulation and drug delivery challenges for biopharmaceuticals – Novel vs. traditional approaches for new products
14:30 Exhibitors highlights
15:30 Coffee break, Exhibition and Posters
16:00 Glycocconjugate vaccines against bacterial infections based on
Prof. Peter Seeberger | Max Planck Institute of Colloids
16:30 Formulation and process development considerations for
oligonucleotides intended for intrathecal injection
Rob Simler | Associate Director, Biogen, USA
17:00 Concluding remarks
17:10 Conference ends
The key roles of formulation and orthogonal analytical methods in the success of biopharmaceuticals
Prof. Tudor Arvinte | University of Geneva, Chairman & CEO, Therapeomic Inc, Switzerland
A good formulation is a key factor for the success of a biological drug from beginning to end, at both the research and drug product development stages. A frequent mistake in the biopharmaceutical research and development in industry as well as in academia, is to consider that protein formulation activities are straightforward and a matter of routine. The complexity of physical and chemical properties of proteins in vitro and in vivo, and their interactions with formulation ingredients, strongly influence the stability of the formulation, as well as the biological activity of the biopharmaceutical. Many sensitive, orthogonal analytical methods are required to characterize the molecules and their stability in vitro in the complex formulation environments. Development of analytical methods for formulations and formulation activities should start as early as possible in a project. Using case studies, the formulation approach developed by our team will be presented. It consists of three platforms: i) high-throughput analysis (HTA), ii) high-throughput formulation (HTF) and iii) studies of aggregates formation after mixing of biopharmaceutics with human plasma and human blood. The importance of assessing the compatibility of a therapeutic protein formulation with human plasma during product development will be discussed.
Formulation development challenges of bi-specific antibodies
Stephanie Davies | MedImmune, UK
Currently, there is an increasing number of research and development programmes within the biopharmaceutical industry exploring the use of bispecific antibodies (BsAbs) for the treatment of autoimmune and infectious diseases. The largest number of BsAbs in clinical trials however are for the treatment of various cancers. One advantage BsAbs possess over conventional monoclonal antibodies (mAbs) is their ability to bind simultaneously to two different antigens or two different epitopes on one antigen. The ability of dual specificity allows multiple disease pathways to be targeted with one molecule which is an advantage over combination therapies where two (or more) mAbs may be required for successful treatment. Although BsAbs have the potential to outperform mAbs in the clinic, there are a multitude of challenges faced during their development. Low expression yields and low recoveries and are commonly observed during fermentation and purification processes and challenging stability profiles are often encountered during formulation development. This presentation will discuss the challenges faced with a BsAb currently in development at MedImmune. A brief overview of BsAb formats and the rationale behind format selection for this particular molecule will be discussed, as well as the chemical and physical instabilities which are observed and the characterization work performed to understand and mitigate these degradation pathways.
Stability challenges with ADCs
Adithya Balasubramanian | Lonza Drug Product Services, Switzerland
For the past 25 years, monoclonal antibodies (mAbs) have been widely used for various therapies. In the ever-changing landscape of new biologicals, antibody-drug conjugates (ADCs) are one of the fastest growing classes of drugs for oncology treatments. Complex structure of ADCs, with the mAb, linker and cytotoxin, together with instability of the structure affects the mechanism of action (MOA) and increases drug related toxicity. To achieve desired therapeutic effects of an ADC molecule, the overall structure and the stability of the molecule is very crucial. Apart from ADCs, there are new mAb derived formats, including and not limited to bi-specifics, mAbs with extended regions, fusion proteins comprising Fc, Fab fragments alone, nanobodies and many other formats being introduced to the clinic at very high pace. Due to stability related challenges, newer iterations of these formats are constantly being developed. Maintaining stability of a biological molecule has always been a challenge for Drug Product development. Various challenges faced during development of a stable Drug Product of ADCs and other newer formats will be discussed.
Development of parenteral multidose products – the challenge of preservatives
Helen Sjögren | Ferring, Denmark
A steady increase in biologicals and hence parenterally delivered drugs has led to rise in demand for various drug delivery systems that ensure ease of administration and cost containment. Multidose delivery of parenterals are desired when repeated dosing is required as it offers convenient administration as well as cost effective products. With few exceptions, multidose parenterals incorporates a chemical preservative. Including preservatives often introduce additional challenges in drug development. The most commonly used preservatives in biologicals are metacresol, phenol and benzyl alcohol. It is well-known that these preservatives negatively impact stability of many proteins. Adding preservatives may also cause other issues with product stability. It is shown that presence of preservatives and other excipients like buffers and stabilisers can trigger degradation processes resulting in discoloured solutions. Additionally, in certain concentration ranges, these preservatives trigger phase separation when mixed with nonionic surfactants. It is a regulatory requirement to prove the efficacy of the preservation system in a multidose product. This is done by the efficacy of antimicrobial preservation test method where the product solution is inoculated with microbial suspensions and the fraction of microbes alive is determined. The preservation efficacy is not only depending on the concentration of the preservative, but also on other components in the formulation. It has previously been shown that interaction between peptides and preservatives reduce the preservation efficacy. This has also been proven to be the case for various excipients as surfactants, buffers and stabilisers. The effect varies with both excipient and preservative used.
Glycocconjugate vaccines against bacterial infections based on synthetic glycans
Prof. Peter Seeberger | Max Planck Institut of Colloids and Interfaces, Germany
Most pathogens, including bacteria, fungi, viruses and protozoa, carry unique sugars on their surface. Currently, several glycoconjugate vaccines against bacteria are successfully marketed. Since many pathogens cannot be cultured and the isolation of pure oligosaccharides is difficult, synthetic oligosaccharide antigens are an attractive alternative. In this plenary lecture I will describe a medicinal chemistry approach to the development of semi- and fully synthetic glycoconjugate vaccines against severe bacterial infections, including resistant hospital microorganisms. This approach is fueled by oligosaccharides prepared by automated glycan assembly that has been commercialized. Quality control of synthetic oligosaccharides is ensured by ion mobility mass spectrometry (IM-MS). Vaccine programs aimed at protection from a series of Streptococcus pneumoniae serotypes, Clostridium difficile and Klebsiella pneumoniae have progressed to the late preclinical stages and are now advanced to the clinic by Vaxxilon AG. Synthetic oligosaccharides serve as basis for tools such as glycan microarrays and for the production of monoclonal antibodies.
Formulation and process development considerations for oligonucleotides intended for intrathecal injection
Rob Simler | Biogen, USA
The development of a parenteral therapeutic intended for intrathecal administration must include special considerations unique to this route of administration. Dosage form selection, particularly during early phase clinical studies, needs to accommodate a wide range of dosing scenarios while minimizing pharmacy manipulation during dose preparation. Additionally, intrathecal therapeutics must meet extraordinarily tight endotoxin levels, in some cases with specifications tighter than those used for Water for Injection. This talk will focus on the formulation considerations and process development controls needed to develop a parenteral intrathecal therapeutic. This will include an end-to-end risk assessment approach to establish proper endotoxin controls in a manufacturing process that can be broadly applied to the control of any critical quality attribute for other molecules. The development of antisense oligonucleotide therapies (ASOs) intended for intrathecal injection will be used as case studies to illustrate these considerations. Additionally, as ASOs are synthetically derived small molecules, differences in the approaches to formulation and process development of ASOs as compared to biologic therapeutics will be presented. Specifically, leveraging the inherent stability of this class of molecules to streamline development will be discussed. The establishment of process parameter ranges and the impact to the assessment of their criticality in an ASO drug product manufacturing process will be highlighted.