7th European Biosimilars Congress May 15-16, 2017 Munich, Germany

Zapata C is a Medical Doctor interested in the evaluation of the relationship between serum levels and therapeutic efficacy in the use of biological drugs as well as the determination of immunogenicity in the clinical setting related to use of these molecules. Currently, he is working in the research group of therapeutic evidence, Faculty of Medicine, Universidad de La Sabana under the coordination of Dr. Rosa Bustos. In addition, he has participated in speeches and conferences regarding the safe and cost effective use of biological drugs in Colombia.

Rheumatoid Arthritis (RA) is an inflammatory disease of the joints that affects a large number of people worldwide. This condition can lead to debilitating joint destruction through the erosion of cartilage and bone. One of the pharmaceutical interventions for the treatment of this pathology are the biological disease-modifying anti-rheumatic drugs (DMARDs) that are directed toward inhibiting the cellular immune response responsible for the inflammation. TNF inhibitors were the first of the biological DMARDs to be approved for the treatment of RA and have become part of the routine treatment of patients with this disease. During the last years, the therapeutic drug monitoring of adalimumab and other biosimilar anti-TNF drugs have been an important tool to optimize the outcomes and costs of treatment, because the wide variations in their serum concentrations cannot be explained by classic pharmacokinetic factors and they are associated with therapeutic failures, anti-drug antibody formation, presence of adverse reactions, over dosage and in many cases treatment drop out. The methods for measurement of these drugs are expensive, with very high analysis time and for some molecules with low sensitivity and specificity. Biosensors is a nano-biosensor technology used for the study of interactions in real time, with advantages in the speed of analysis time, without the use of markers or developers and complying with the harmonization standards for biological analytical methodologies, allowing to customize the therapy and the use of concomitant immunomodulatory treatment. The objective of this study is to develop a real-time methodology through the use of an optic biosensor for the serum quantification of anti-TNF alpha in patients diagnosed with rheumatoid arthritis treated with anti-TNF alpha therapy.

Biologics are an important class of targets in drug discovery that are proven to be effective therapeutics. However, characterization of biologics and the associated workflows from early discovery to final formulation can often be very complex, time-consuming and lack accuracy and precision needed to appropriately monitor drug candidates. Here we demonstrate that the Prometheus NT.Plex by NanoTemper Technologies can be used for long-term stability prediction of biologics using a combination of thermal and chemical unfolding analysis. The resulting unfolding data nicely correlates with sample turbidity and monomer content over a time period of 17 months, showing that the Prometheus NT.Plex can be used to rapidly predict the long-term stability of biologics within one day. Moreover, we evaluate the performance of the Prometheus instrument compared to μDSC measurements in a thermal stability screening analysis. We show that the Tm-values obtained by the Prometheus NT.Plex show a strong correlation with μDSC data, while dramatically reducing sample consumption and time-to-results. The Prometheus NT.Plex combines the easy-to-use and highly precise detection of protein thermal and colloidal stability measured by the Prometheus NT.48 with a flexible and fully automated, interface, the NT.Robotic Autosampler. High-precision capillary chip handling and filling is carried out automatically from 384 well plates, so that the Prometheus NT.Plex can continually run with minimal manual interactions. Hundreds of samples can be measured per day, enabling stability screening with an unprecedented throughput and accuracy. This platform provides robust, efficient and accurate analysis and characterization of biologics.

Katsuyuki Takeuchi is a Manager of Business Development in Pharmaceutical Solutions, Terumo Corporation, Japan. With extensive knowledge in Pharmaceutical Science, he has worked in research and development of injectable drug products such as IV bags and prefilled syringes, and contributed to launch several products into the market. Utilizing his experience, he is now working on introducing polymer based prefillable syringes to the pharmaceutical industry.

Aggregation of therapeutic proteins is one of critical risk factors since it may impact negatively on the drug efficacy and safety due to the protein deactivation and immune responses in patients. In 2014, US FDA published a guidance entitled “Immunogenicity assessment for therapeutic protein products” recommending industry to minimize protein aggregation to the extent possible. Silicone oil has been widely used as a lubricant for prefillable syringes to achieve smooth plunger gliding functionality. However, for biopharmaceuticals, silicone oil can have a serious impact because it can induce protein aggregation. This became one of the topics frequently discussed, particularly for developers of highly sensitive biopharmaceuticals. To mitigate the risks related to silicone oil, the demand for a silicone oil free system is surging, and various technologies are now proposed. i-coatingTM developed by Terumo is a coating on the stopper surface having a strong and flexible layer of silicone resin and is applied through a chemical process, including polymerization of the layer. In this poster, the functionality of a newly developed silicone oil free prefillable syringe system using a cyclo-olefin polymer (COP) based barrel and i-coatingTM plunger stopper is presented and compared to silicone lubricated PFS systems. Silicone oil related particles and particles related to protein aggregation are significantly lower in the silicone oil free syringe system. Furthermore, in contrast to a silicone oil lubricated COP syringe system, the silicone oil free system shows no remarkable changes in break loose peak force and it remains stable over time; tests were conducted under various storage temperatures. These findings suggest that silicone oil free syringe system offer favorable performances for silicone oil sensitive drugs, leading to less risk of immunogenicity as pointed out by the FDA guidance.

Özgenur Erdokur. I was born in Bursa on 2 Nisan 1993. I studied at Ege University, Faculty of Science, Department of Chemistry between 2011 to 2016. I have participated in various congresses such as participating the organizing committee of the 6th National Chemistry Students Congress and the in vivo cancer imaging course which organized in 2015 in Ege University, Center for Drug Research & Development and Pharmacokinetic Applications (ARGEFAR). I have started postgraduate since 2016 in Ege University, Division of Physical Chemistry and also worked in ARGEFAR. I am charge of the In Vivo Imaging Sistem (IVIS) device with my supervisor Assoc.Prof.Dr.Yeliz Yıldırım who is consultant of devise which is located in Prephase research unit of ARGEFAR. IVIS has many uses, and our laboratory has a wide range of applications. There are a lot of project continue in our laboratory especially cancer disease, so I have worked on these issues many times. The Prephase imaging and bio-similarity researches are of great importance for the drug development process. I want to improve on this subject myself with great enthusiasm to become a good academician.

Cancer disease causing uncontrolled cell division is one of the crucial research areas. Cancer types such as lung, prostate, stomach, colon, and over are most common. Chemoprevention as the use of natural or synthetic chemicals to prevent from cancer disease has been investigated by several groups in the literature. There are a lot of scientific discovery about natural product agents such as vegetables, fruits, mushrooms, yeast, fungi, algae for potential new anticancer drugs. Algae survive in a large scale in the earth: in the sea, rivers, and lakes, on the land, on the other organism. Some bioactive compounds obtained from seaweeds have the ability to inhibit the growth of different cancer cells. They can be employed as cancer chemopreventive and/or chemotherapeutic agents. In this study, in vivo anticancer effects of Halopteris scoparia Sauvageau (brown algae) as an anti-cancer drug has been evaluated against A549 human lung cancer cells. H.scoparia was collected at a depth of 1-2 m, from the coastline of Urla, Izmir, in April 2012. The samples were washed three times with tap water and maintained in a refrigerator at -20°C. Five-week-old male nude mice were divided into three groups: control, 900 mg/kg algae treatment (everey day, p.o.) and 2 mg/kg cisplatin treatment (twice a week, i.p). A549- luciferase human lung cells (1-2 x 106 cells/site) were injected subcutaneously into the left or right side of the mice legs. Anti-cancer properties of H. scoparia algae were examined by using bioluminescence imaging (IVIS spectrum) during four weeks with tumor volume and animal weight measurements. In vivo bioluminescence imaging uses luciferase enzymes as reporters to generate light emission during the catalytic oxidation of their substrates for noninvasive imaging of biological targets and processes in living animals. Consequently, the results show that anti-cancer activity of H. scoparia is similar to cisplatin which is used commonly chemotropic agent.

Rodica Olteanu is a Dermatologist and Medical Director of Colentina Clinical Hospital, Bucharest, Romania. She received her PhD in 2007 from Hamburg University. She is involved in autoimmunity and immunogenicity of biologics and biosimilars. She has published more than 100 papers related to lupus and psoriasis. She is the winner of many international grants, member in EADV Project Committee, AAD, GRAPPA, EuSCLE, SRD and ILDS. She completed her educational training from Barcelona and has also visited many institutes as an Invited Speaker.

Biosimilars represent a new tendency in the treatment of many immune-mediated inflammatory diseases, including psoriasis. Regulatory requirements for approval of biosimilars are different from those of originators and rely mostly upon the evidence generated from bioequivalence studies and in particular from RCT, as an important part of it. In our study, case series, we tried to correlate the immunogenicity (measured with ELISA method: Antidrug antibodies and drug level) on 8 patients on Inflectra (infliximab biosimilar), treated more than 8 months in our Dermatology Clinic. Our goal was to determine the evolution of the inflammatory markers (ESR, PCR) together with the evolution of PASI, PASI50 and PASI 90 in a case series of 8 patients for 8 month. We were also capable of evaluating the possible correlations between these indices and immunogenicity. We found an interesting fact that from these 8 patients, 2 had sub-therapeutically drugged level but not anti-infliximab antibodies. One of these 2 patients had also elevated inflammatory markers and the other one has gained more than 10 kg. It was also observed that the third patient developed anti-infliximab-antibodies as well as sub-therapeutically trough level of infliximab. Two months later we evaluated the same parameters and we found no anti-infliximab antibodies. There are some discussions in the literature regarding the transient anti-drug antibodies and therefore the need to repeat them when positive and mainly when the clinical appearance does not explain the paraclinical findings. Our study concluded that, even on small clinical trial you can find valuable information that can help to tailor the treatment for the patient.