4th International Conference and Exhibition on Biologics and Biosimilars October 26-28, 2015 Baltimore, USA

Biography:

Gene M. Ransom, III is CEO of the largest physician organization in Maryland, MedChi, The Maryland State Medical Society. As MedChi executive, Ransom implements MedChi’s mission as an advocate for physicians, patients, and the public health of Maryland. MedChi currently represents over 7,500 Maryland physicians, created several Accountable Care Organizations, and operates one of Maryland’s largest Insurance Agencies. Ransom has worked hard on key public health issues like protecting Medicaid, promoting public health programs, and insurance reform in his role as director. Ransom is a life-long resident of the Delmarva Peninsula and was elected to the Queen Anne's County Commission in November 2002. Ransom was the only incumbent County Commissioner re-elected in the 2006 election. Ransom graduated from The University of Maryland with honors in economics and the University of Baltimore School of Law. When elected, at thirty-one, Ransom made history as the youngest Commissioner ever to serve Queen Anne's County. During his term as Commissioner he fought for fiscal responsibility, managing a budget of over 100 million dollars and voting for a balanced budget every year in office while reducing the Queen Anne’s property tax rate by over twenty cents during his two terms. Ransom was an instrumental part of a bipartisan effort to bring the first full service twenty four hour emergency room to Queen Anne’s County.

Abstract:

Biography:

Gordon T Bolger received his BSc in Biochemistry from McGill University and a PhD degree in Molecular Pharmacology from the State University of New York. He then held key positions at the National Institutes of Health as Assistant Professor at Memorial University of Newfoundland and with Boehringer Ingelheim Research and Development, Canada. He possesses extensive experience in the preclinical drug development area with key expertise in evaluating the pharmacodynamics and pharmacokinetics of candidate drug molecules. He has authored /co-authored 95 publications and 53 scientific communications. Presently, he is a Senior Scientist / Study Director at Nucro- Technics, a pharmaceutical contract research organization.

Abstract:

This study utilized safety, pharmacodynamic and pharmacokinetic data to compare the biosimilarity of the human recombinant erythropoietin (EPO) products ior®EPOCIM and Eprex® following a 28-day repeated intravenous dose administration in male and female Sprague-Dawley rats with a 14-day recovery period. Safety profiling was based on clinical observations, clinical pathology and pathology findings for control rats dosed with vehicle and rats dosed either with 30, 300 and 600 I.U./kg of ior®EPOCIM or 600 I.U. of Eprex®. Adverse findings for both ior®EPOCIM and Eprex® were similar and were a consequence of thrombotic events (ulcerative skin lesions, swollen hock joints/lameness, stomach ulcers) and decreased body weight gains, all known adverse reactions to this class of drug in rats. With the exception of stomach ulcers, all other adverse findings were fully reversible with a similar time course for both products. Neither drug stimulated the production of anti-drug antibodies. As expected, iorEPOCIM® and Eprex® both increased reticulocyte, red blood cell, hemoglobin, and hematocrit levels in rats to a similar extent. The pharmacokinetics of EPO following dosing with either ior®EPOCIM or Eprex was well behaved, displayed bioequivalence and was consistent with the literature. The results of this study imply that ior®EPOCIM and Eprex® had safety profiles, pharmacodynamic responses and toxicokinetic profiles that were consistent with biosimilarity for both products.

Biography:

Dr.Manjunath is a Research Scholar at the Department of Dravyaguna KLEUs BMK Ayurveda medical college Belgaum, India. His research interests include drugs derived from plant and other natural sources and their adverse drug reactions.

Abstract:

Drug safety is a very basic and fundamental concept in medical practice. ADRs play an important role in assessing patient safety in any system of medicine. Pharmacovigilance study is thus significant to understand treatment outcomes. Current raised issue with respect to complementary and alternative system medicine (CAM) like Ayurveda is increased in number of safety reports along with report misinterpretation; this generates the negative impact on system. Although, Ayurveda which is holistic system of medicine from India has elaborated the causes and methods of drug induced consequences along with preventive measures the available data in classical texts is scattered. The compilation and analysis along with modern concept drug safety is need of the hour. Present literature review was conducted from various compendium of Ayurveda and electronic data base with search terms of ‘Vyapad’, ‘Viruddha’, ‘Ahita’, ‘herb-herb interaction’, ‘idiosyncrasy’, ‘Prakritiviruddha’ etc. The reported information was analyzed for the possible correlation on concept of ADR and Pharmacovigilance of current science. Overall review demonstrated that drug interaction, iatrogenic, over dose, administration of unsuitable drugs, reprehensive drug administration with respect to disease, complication from five procedural therapies (Panchakarma) and reprehensible preparation of mineral drug are nearer to the modern causes of ADR. Thus, concept of drug safety and ADR is not new to the Ayurveda. The concept “Drug which is not appropriate to be used as medicine”(Abheshaja) of Ayurveda sounds similar as that of modern pharmacovigilance.

Biography:

Adetunji, Olawale is a Ph.D. holder, Medical Microbiologist and Chief Lecturer at the Osun State Polytechnic, Iree. Nigeria. His research activities include; Medical Bacteriology, Environmental Microbiology and Public Health Microbiology. He has made some modest contributions in these major areas of Microbiology with notable publications in peer reviewed learned national and international journals. His current publication include; Olawale, A. K., David, O.M., Oluyege, A.O., Osuntoyinbo, R.T, Laleye, S.A. and Famurewa, O. (2015). Histopathological changes induced in animal model by potentially pathogenic Enterococcus faecalis strains recovered from ready-to-eat food outlets in Osun State, Nigeria. Infection and Drug Resistance, 8: 181-187.

Abstract:

Biocides are an essential part of infection control practices and aid in the prevention of bacterial infections. This work investigates the antibacterial effectiveness of four brands each of disinfectants, antiseptic and ordinary soaps purchased from different supermarkets in Osogbo and Ado-Ekiti, Nigeria against selected Enterococcus faecalis strains, using standard methods. The disinfectants include; Septol, Dettol, Purit and Izal. The soaps assessed were: Medisoft, Robert, Tetmosol, Tura, Lux, Morning fresh, Mama- gold, and Canoe. Two of the disinfectants (Septol and Purit) had the highest growth inhibition of the test isolates (55% and 65% respectively). Antibacterial effectiveness of ordinary soaps; Mama-gold, Morning-fresh, Premier and Lux were recorded as 10%, 15%, 15% and 20% respectively, followed by antiseptic soaps (Medisoft 30%, Tura40%, Robbert 35% and Tetmosol 50%). The effect of holding time on the rate of kill of soaps and disinfectants does not show any significant difference except in Purit with highest at 100 seconds. This research concludes that disinfectants have higher prevention potency on enterococcal pathogens with high records of inhibition (55% and 65%) of Septol and Purit on Enterococcus faecalis strains as against the inhibition of antiseptic soap, Tetmosol (50%) and ordinary soap, Lux (20%). Hence, the use of disinfectants and antiseptic soaps should be encouraged in our food canteens, to prevent the spread of enterococcal infections.

Biography:

Neha Gulati has completed her M.Pharm in 2011 and pursuing PhD from IFTM University in Pharmaceutics. She has been awarded silver medal in B.Pharm and Academic Excellence Award. She has published more than 25 papers in journals of repute and has been serving as an editorial board member of repute.

Abstract:

In the biopharmaceutical market, therapeutic recombinant proteins are the noteworthy and rapidly inflating segment. Molecular types of these recombinant proteins can basically comprises of anticoagulants, blood factors, engineered protein scaffolds, enzymes, growth factors, hormones, interferons and interleukins. These are fabricated in bacteria, yeast, filamentous fungi, insect cells, mammalian cells and transgenic plants. Foremost manufacture of 38 percent recombinant proteins is achieved by E. coli, 36 per cent by CHO cells, 16 per cent by yeasts, 12 per cent by other mammalian systems. In the breakthrough, recombinant protein drugs have upheaval the future for the therapy of several types of cancer and rheumatic conditions. The significant techniques adopted for the manufacture of protein products includes reformulation, pegylation and other forms of modification. Bottom-up and top-down approach are major for the fabrication of recombinant proteins. The potential business of therapeutic proteins have stated a major change with improved efficacy, greater safety, and reduced immunogenicity. The conventional pharmaceutical manufacturers will have to concentrate for these future biologic products. It will be a big assessment to bring about the innovation, to achieve untained, secure, cost effective and high yielding recombinant human therapeutic proteins with superiority.

Biography:

Dr Manjeeta Gupta, is currently a third year postgraduate student pursuing MD Pharmacology at MIMER Medical College Talegaon Dabhade Pune, Maharashtra, India. She has completed her Bachelor in Medicine Bachelor in Surgery (MBBS) in 2010 from BVP Deemed University, Pune, Maharashtra, India. She has also done a one month internship (February 2015 - March 2015) at National AIDS Research Institute, Pune, India. She was awarded third prize in Oral Presentation on “Newer drug delivery systems in geriatric age group” in GERICON 2014, Lonavala, Maharashtra, India.

Abstract:

Background: Drug-drug interaction (DDI) is a specific type of adverse event, which develops due to multiple drug therapy, especially in critically ill-patients. Aim: To study the prevalence of potential DDI, their severity, clinical significance, and their association with patient characteristics in Intensive Care Unit (ICU) patients in a tertiary care hospital. Material and Methods: A prospective, observational study was conducted for a period of 3 months (July 2014 -September 2014) to assess the potential DDIs using Medscape Drug Checker Software and Lexi-Comp, Inc. Version: 2.7.5. drug interact android mobile application. Results: A total of 180 patients, majority of which were suffering from cardiovascular conditions (30%) were included in the study with a prevalence of 77.78% potential DDIs. In those with hospital admission more than five days, 65.73% had potential DDIs. There were 229 potentially interacting drug pairs with corticosteroids, aspirin, beta blockers, and diuretics being commonly involved in potential drug interactions. A total of 2336 interactions were observed with an occurrence rate of 3.08 DDI per patient. Severity was moderate in 64.63%, pharmacodynamics mechanism in 72.49%, and 60.26% had risk rating category C. Conclusions: The present study showed high concomitant drug administration of potentially interacting drugs. The prevalence confirmed the association of polypharmacy and duration of hospital stay. Vigilant prescribing approach is needed to prevent hazardous outcomes of DDIs.

Biography:

Afshin Safavi, PhD, Founder and CSO at BioAgilytix, is a veteran biochemist with extensive experience in establishing and leading bioanalytical teams in support of the development of biological products in preclinical and clinical-trial laboratories. Prior to founding BioAgilytix Labs, he was the Director of Ligand Binding and Immunoassay. At Grifols, he led the Preclinical and Clinical Assay Development team, building on his experience as a senior scientist at Nobex Corporation, GlaxoSmithKline and IGEN International. He is considered an expert in the area of immunoassay with a wide working knowledge of various platforms.

Abstract:

Biosimilars are entering the landscape as patents for major branded large molecule products start to expire over the next few years. This rapid drive is fueled by the potential to reduce treatment costs and increase the accessibility of treatments for everyone around the world. However, generation and approval of biosimilars are not trivial as a biosimilar medicine is essentially a new biological product that is similar (not identical) to a medicine that has already been authorized to be marketed. In this presentation, I will review the bioanalytical challenges and solutions that apply specifically to the analysis of biosimilars in biological samples with a focus on the PK, immunogenicity, biomarker and cell-based assays.

Biography:

Mariana Babayeva MD, PhD is an Associate Professor at Touro College of Pharmacy, New York, NY. In addition to her role at Touro, Dr. Babayeva is also an Adjunct Professor at RockefellerUniversity and Visiting Scientist at Arnold and Marie Schwartz School of Pharmacy of LIU.Dr. Babayeva has over 10 years of experience in clinical practice. She is recognized for her expertise in the pharmacokinetics and the use of animal and organ models. Dr. Babayeva has conducted several international research projects. Dr. Babayeva has been published in peer-reviewed journals and serving as an editorial board member of repute.

Abstract:

The effect of protein binding interaction may result in clinically significant changes in the pharmacokinetics and pharmacodynamics of a drug.A goal of this investigation was to evaluate the potential for inhibition of warfarin plasma protein binding by tizoxanide.Warfarin is a widely used anticoagulant and has a narrow therapeutic index. Tizoxanide is an active metabolite of a rapidly hydrolyzedanti-infectiveprodrug nitazoxanide. Warfarin and tizoxanideare highly bound to plasma albumins. Nitazoxanide is a compound that expected to be co-administered with warfarin and have the potential to alter warfarin protein binding. Such protein binding interaction can result in displacement of warfarin from the protein binding site, increase free plasma concentrations and raise the risk of bleeding. Plasma protein binding of warfarin was evaluated using ultrafiltration. The studies were divided into two phases. Phase I studies generated baseline protein binding values for warfarin. Phase II studies was conducted to assess the effect of tizoxanide on warfarin protein binding. Experiments were conducted over a range of warfarin concentrations. Studies were carried out at physiologic temperature and pH.Samples were analyzed by HPLC. The warfarin fractions unbound were significantly higher in the interaction studies (Phase II) compared to the values of the warfarin alone studies (Phase I). Mean fraction unbound of warfarin in Phase I studies was 0.012, in Phase II studies 0.31. Coadministration of tizoxanide significantly increased free fraction of warfarin for all concentrations tested. This interaction might increase the risk of side effects associated with warfarin administration.

Biography:

Andy was a founding member of BioOutsource having a fundamental role in the concept of the business, Andy has developed since 2003 an in-depth knowledge of Bioassays gained from his current position at BioOutsource as Head of the Research and Development and also Custom projects and from his previous position as Study Director with Covance Laboratories in Harrogate Yorkshire where he had a leading role in the Bioassay group. Andy holds a BSc (Hons) degree in Biochemistry and an MSc in Neuroscience. His vast experience of different molecules has given him an expert knowledge on the analysis of Biological potency assays for batch release and the detection of Anti-drug Antibodies. Andy also plays a key role in the marketing strategy for the company.

Abstract:

The model for bringing a biosimilar drug to market is evolving; the regulations have required manufacturers to establish similarity based on multiple analytical methods - comparing this to the Reference Medicinal Product (RMP). However looking forward the FDA have introduced the concept; "highly similar with finger-print like similarity”, as the “gold standard” for similarity and will be viewed in a crowded market of many different biosimilars, as key to successful uptake of the drug by clinicians and patients. For manufacturers of biosimilar monoclonal antibodies, one of the greatest obstacles to meeting fingerprint like similarity is the creation of a product with the desired ADCC (Antibody-Dependent Cell–Mediated Cytotoxicity) profile, the recent approvals for Remsima demonstrates this is a continuing issue. Measuring ADCC activity relies on mimicking in vitro, the activation of innate constituents of the immune system, this is a complex stepwise series of events that can be influenced by a multitude of factors. The importance of these constituents of these steps in the immune system are slowly becoming more understood and with recent improvements in analytical methodologies we are now able to tease apart the individual interactions and better understand the ADCC potential of biosimilar monoclonal antibodies. Using ADCC data obtained from a comparison of Remicade and Remsima, this presentation will highlight the requirement for a suite of highly sensitive, orthogonal methods that can be applied at varying stages of development that allow identification of potential differences between biosimilar and RMP, prior to the application of methods with increased biological relevance to determine the potential impact on clinical efficacy or safety.

Biography:

Dr Samantha Little is a Lead Scientist within the BioPharmaceutical CMC Solutions Division at Covance, a global drug development company, where she has worked since 2009. She has experience in CMC methodologies to support drug development of Biologics including ADCs and Biosimilars and has been a member of the Global Bioanalysis Consortium Harmonisation Team for Large Molecule Run Acceptance. Previous to Covance, Samantha worked as a Senior Scientist for a biodefense company and a post-doctoral fellow at the Hull York Medical School researching proteomics and angiogenesis. Samantha has a PhD in analytical chemistry.

Abstract:

To support a claim of Biosimilarity, the EMA and FDA are interested in the ‘totality of evidence’ where the molecule and its physicochemical and biological attributes are assessed from the perspective of clinical relevance. The assays used in these assessments need to have the ability to identify where changes in the molecule are key to clinical efficacy. There is no type of assessment which alone is capable of verifying biosimilarity. As such an orthogonal approach combining physicochemical and functional analysis is required. Results from this approach should be reflective of a molecules critical quality attributes and should hopefully minimize the extent of any clinical studies required for verification of biosimilarity, safety and efficacy. A large challenge for Biosimilars is understanding the structural function association as it relates to the activity of the antibody. Characterisation of IgG1 glycosylation has been shown to be of utmost importance, as it can impact the mode of action. We present a case study which exemplifies how identification of critical quality attributes linked to the known mode of action could have mitigated risk to a Biosimilar development program at the CMC characterisation stage. A CMC strategy has been employed to link quantitification of glycosylation with the mode of action.

Biography:

Mario DiPaola is CSO and co-founder of Blue Stream Laboratories, Inc. He holds a PhD in chemistry and also an MBA and has been in the biopharmaceutical industry for 20 + years in various roles from scientist to company executive.

Abstract:

Glatiramer acetate, the active ingredient in the multiple sclerosis drug, CopaxoneTM, developed by Teva is a complex mixture of synthetically produced polypeptides composed of four amino acids, which include glutamic acid, alanine, tyrosine and lysine at a molar ratio of 0.141, 0.427, 0.095, 0.338. Initiation of the synthesis of the polypeptides requires the addition of diethylamine which results in the partial capping of the carboxy-termini. Blue Stream Laboratories has developed a series of analytical and mass spectrometric approaches to analyze the heterogeneity of the carboxy-termini of glatiramer acetate. Such methods and the analysis of several lots of glatiramer acetate to assess comparability between originator and biosimilar lots by these methods will be discussed.

Biography:

Dr Brijesh Kumar has completed his Ph.D from Central Drug Research Institute, Lucknow (Dr RML Avadh University Faizabad, UP. He is the Senior Principal Scientist and Facility In-charge of sophisticated analytical Instruments facility CSIR-CDRI, Lucknow, a premier drug research organization. He has published more than 81 papers in reputed journals. His current area of research is application of Mass Spectrometry tools (DARTMS/Q-TOF LCMS/4000 Q Trap LCMS/Orbitral LCMS) for qualitative and quantitative evaluation of known and unknown small molecules for quality control and authentication of Indian Medicinal Plant/parts. He is also involved in identification of marker compounds using statistical software.

Abstract:

Herbal medicines, also known as botanical medicines or phytomedicines, refer to the medicinal products of plant roots, leaves, barks, seeds, berries or flowers that can be used to promote health and treat diseases. Today, a vast range of drugs are either natural products or have been derived from them. Moreover increasing sales of herbal products indicate a worldwide concurrent surge of natural product use. Chemical fingerprinting has been demonstrated to be a powerful technique for the quality control of herbal medicines. A chemical fingerprint is a unique pattern that indicates the presence of multiple chemical markers within a sample. Similarly Natural products containing inherently large structural diversity are still a major source of bioactive agents. However many bioactive compounds have been re-discovered from new sources of natural products. To avoid it the identification of known leads at the early discovery step is highly desirable, a process known as dereplication. This method provides an efficient tool for rapid and precise identification of molecular formula of small molecules, with some characterization of sub structures, without a cumbersome process of compound isolation. Application of HRMS and hyphenated LCMS techniques for qualitative and quantitative study of bioactive phyto constituents in Indian Medicinal Plants/parts/products ( P.betle, A.paniculata, Ocimum and Rauvolfia ), with their variations and identification of makers will be discussed during the seminar.

Biography:

Dr.Dineshkumar has completed his Ph.D at the age of 31 from Vellore Institute of Technology, also he was a Junior Research Fellow (DST-Funded). His Ph.D thesis on Studies on snake venom of Indian cobra and Drug Discovery and JRF topic was Exploring the structure and functional relationship of basic poly peptides from Elapidae venom. He has handled all chromatography techniques, Circular Dichrosim etc. After his Ph.D, he had joined as Senior Scientist in Virchow Biotech Pvt Ltd in India and involved in Research& Development for process development and technology transfer for the production of recombinant Urate Oxidase for Gout disorder. Later he Joined Micro therapeutic Research Lab Pvt, India and he developed recombinant human parathyroid peptide for osteoporosis disorder. Finally he worked and developed technology transfer for the production of recombinant Streptokinase for Myocardial Infarction.

Abstract:

Native streptokinase is usually prepared from culture of Streptococcus equisimilisfor therapeutic purpose of intravenous thrombolytic agent for the treatment of myocardial infarction. The N-terminal amino acid of native streptokinase starts with Isoleucine (I), Alanine (A), Glycine (G) and followed by Proline (P) etc. The first of amino acid of Isoleucine is playing an important role for the catalytic activity of streptokinase is binding towards inactive plasminogen to activate plasminogen. The specific activity of native streptokinase is 100000 IU/mg with the initial N- terminal isoleucine amino acid. Despite the recombinant streptokinase of N-terminal amino acid begins with methionine and it is a proteinogenic for E.Coli expression. Comparison for specific activity of recombinant streptokinase shows only 85000IU/mg than 100000IU/mg native streptokinase. The reason behind this objective is that there are two forms (Isomers) of streptokinase are expressed in E.Coli which was analysed by RP-HPLC and chromogenic assay. We have found that this variation is formed by isomer-1 has 85% of Streptokinase expressed without methionine (85000IU/mg) and Isomer-2 has 15% of streptokinase expressed with methionine (nil activity) in E.Coli. This Phenomena is clearly demonstrating that the presence and absence of methionine in isomers are varying the streptokinase activity. Hence the methionine alters the streptokinase catalytic activity and is an important role for both activity and immunogenic. This is the first attempt to explore the methionine variation by our method development on RP-HPLC and chromogenic assay for improving the suppression of risk management of myocardial infarction.

Biography:

Francesco Marchesi is a renowned scientist at the Regina Elena National Cancer Institute , Italy. His research interests are as that of biosimilars and follow-on-biologics.

Abstract:

Only limited data have been so far published about the use of biosimilar filgrastim in hematologic recovery after ASCT. The aim of this study was to compare the biosimilar filgrastim Zarzio® with the other available formulations of G-CSF in terms of efficacy and safety. From March 2013 to June 2014 we used in our Institution biosimilar filgrastim (Zarzio®, Sandoz Industrial Products Spa, Rovereto, Italy) at dosage of 5 mcg/Kg daily given from day 3 after stem cell infusion for febrile neutropenia prophylaxis and haematologic recovery in 64 consecutive adult patients who underwent ASCT. These patients were retrospectively compared with three historical cohorts: a) 99 consecutive adult patients treated with lenograstim (Myelostim®, Italfarmaco Spa, Milano, Italy) at same dosage and timing in our Institution from January 2009 to February 2013; b) 60 consecutive adult patients treated with peg-filgrastim (Neulasta®, Amgen Spa, Milano, Italy) at dosage of 6 mg single dose at day 3 after stem cell infusion in our Institution from March 2006 to December 2008; c) 79 consecutive adult patients treated with originator filgrastim (Granulokine®, Amgen Spa, Milano, Italy) at dosage of 5 mcg/Kg daily given from day 3 after stem cell infusion in Haematology Unit of Campus Bio-Medico University from May 2008 to June 2014. There is not any statistically significant difference among the four patient cohorts. We analyzed the time of hematologic recovery after stem cell infusion (defined as an absolute neutrophilis count upper than 0.5 x 109/L and a platelets count upper than 20 x 109/L), the occurrence of fever of unknown origin (FUO) in neutropenia, documented infectious episodes and needing of intravenous antibiotic treatment, the number of red blood and platelet transfusions, the days of hospitalization and the transplant-related mortality (TRM). We observed a significantly shorter time to neutrophilis and platelet recovery (P=0.001 and P=0.007, respectively) with a consequent lower median number of platelet transfusions (P=0.001) in the cohort of patients treated with Neulasta®, whereas no difference was observed among the other three groups. Moreover, we did not observe any significant difference among the four patient cohorts for all the other analyzed parameters. No difference in terms of drug-related adverse events was observed in the four patient cohorts with no serious adverse events. Considering the median days of G-CSF injections and assuming a patient median body weight of 60 Kg, the estimated cost for each patient was significantly lower in the Zarzio® group (approximately 73€) when compared with the other groups (approximately 732€ for Myelostim®, 649€ for Granulokine® and 660€ for Neulasta®; P<0.0001). Biosimilar filgrastim (Zarzio®) seems to be substantially equivalent in terms of efficacy and safety to the other G-CSF formulations when used for febrile neutropenia prophylaxis and hematologic recovery after ASCT. However, the use of biosimilar filgrastim consents to significantly limit the costs in this setting of utilization. Further prospective randomized studies are warrant to confirm these results.

Biography:

Vikas Bajpai is pursuing his PhD from CSIR- Central Drug Research Institute, Lucknow. He is senior research fellow (Council of Scientific and Industrial Research, New Delhi). He has more than six years’ experience in working and handling with many hyphenated mass spectrometric techniques. Currently he is engaged with the development of mass spectral fingerprints of natural products to check the different level of variations, adulteration from intact plant part using variousmass spectrometric techniques.

Abstract:

Thalictrum (Ranunculaceae) is very widely distributed genus of medicinal plants in India and has been reported to have many therapeutic properties like diuretic, stomachic, antiseptic, aperient etc. Approximately 290 alkaloids were reported from the 80 species of the genus Thalictrum. Alkaloids from Thalictrum are reported to exhibit various pharmacological activities like antiamebic, antimicrobial, antitumour and antiviral. Protoberberine and aporphine alkaloids are reported the major components in this plant In present study, we present simultaneous quantification of some alkaloids in Thalictrumreniformeusing ultra performance liquid chromatography coupled to hybrid triple quadrupole/linear ion trap mass spectrometry (UPLC-QqQLIT-MS) operated in the multiple reactions monitoring acquisition. The separation was achieved on an ACQUITY UPLC CSHâ„¢ C18 column using a gradient mobile phase at flow rate of 0.3 mL/min. Stock solutions of standards were prepared in methanol within the ranges from 0.5 to 1500 ng/mL.The calibration curves were constructed by plotting the peak areas versus the concentrations of each analyte. Five PBAs were quantified in which Berberine, Jatrorrhizine and Palmatine were detected in significant amount.

Biography:

Dr. Imran Ali Khan has completed his Ph.D at the age of 27 years from Osmania University and presently joined as postdoctoral studies in King Saud University. He has published more than 47 publications in reputed journals. Presently, he is working with multiple projects on relationship between consanguinity and metabolic disorders.

Abstract:

The paraoxonase 1 (PON1) gene polymorphism Q192R has been found to be consistent with multiple metabolic diseases comprising type 2 diabetes mellitus (T2DM). The R allele has been found to be associated with coronary artery disease and gestational diabetes in a Saudi population. Therefore, we attempted to determine the association between Q192R and T2DM in a Saudi population. Eight hundred subjects were enrolled in this case-control study, including T2DM patients (n = 400) and control individuals (n = 400). Epidemiological, clinical, and Q192R genotype data were obtained from all the subjects included in this study. Genotyping was performed by PCR-RFLP analysis followed by 12% polyacrylamide agarose gel electrophoresis. Most of the clinical characteristics of T2DM were associated with controls, having positive association with allele and genotype frequencies between the T2DM cases and controls (p < 0.05). Multiple regression analysis showed positive correlation of lipid profile with genotype (p < 0.05). The present findings provide robust evidence of PON1 Q192R polymorphism being associated with T2DM in a Saudi population.

Biography:

Patrick Lucy is the Chief Business Officer of Pfenex Inc. (NYSE: PFNX). He was a member of the team that founded Pfenex within The Dow Chemical Company. He has been in the biotechnology industry for over 22 years holding technical, operational and commercial roles throughout his career. He previously worked at The Dow Chemical Company, Collaborative BioAlliance, Lonza Biologics, Celltech Biologics and Repligen Corporation.

Abstract:

The United States biosimilars market was established based upon The Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The BPCI Act was formally passed under the Patient Protection and Affordable Care Act (ACA), and signed into law by President Barack Obama on March 23, 2010. The BPCI Act was an amendment to the Public Health Service Act (PHS Act) which created an abbreviated approval pathway known as the 351(k) pathway for biological products that are demonstrated to be highly similar (biosimilar) to a FDA approved biological product. Since March of 2010 there has been a flurry of activity in the US biosimilars market covering all aspects of the path to approval including a set of FDA guidances, 351(k) filings, and varying approaches to the “patent dance”. There has also been an emergence of biosimilar players from pure play biosimilar companies to large multinational pharmaceutical companies establishing divisions devoted to biosimilar development. This presentation will recap the evolution of the US Biosimilar market since the passage of the ACA and will explore the present and future global biosimilars opportunity.

Biography:

Dr. Kamali Chance is a Vice President and Head, Global Biosimilars Regulatory Strategy. She has over 25 years of work experience in the healthcare industry, including the last 17 years in regulatory affairs/regulatory strategy.Dr. Chance has extensive experience working with the FDA and EMA. She advises pharmaceutical and biotechnology companies in the development of region specific and/or global regulatory strategy for the development of biosimilar products. Dr. Chance has authored/co-authored number of articles on the development of biosimilars. She has a PhD in Nutrition/Nutritional Biochemistry, Masters of Public Health and Regulatory Affairs Certification.

Abstract:

The regulatory landscape for the development of biosimilars in the US and EU is dynamic as many of the guidances issued by European Medicines Agency (EMA) have undergone revisions and in 2015, the FDA issued number of revised guidelines for Quality and Scientific Considerations as well as updated Questions and Answers documents that lend much clarity as to FDA expectations.The thinking of the regulators both in the EU and US has evolved over the years and there is a great deal of convergence. This session is designed to provide current status of biosimilar guidelines in the US and EU. The focus will be to identify major updates in order to help sponsors navigate through the complex requirements for the regulatory approval of biosimilars in the US and EU.

Biography:

Alex Brill is the CEO of Matrix Global Advisors, LLC, an economic and public policy consulting firm in Washington, DC. Prior to founding MGA, he served as policy director and chief economist to the United States House of Representatives Committee on Ways and Means, where he worked from 2002-2007 and directed policy development and led staff-level negotiations on a variety of matters. Previously, he served at the White House Council of Economic Advisers. In addition, he is a Research Fellow at the American Enterprise Institute. He holds a BA in Economics from Tufts University and a MA in Mathematical Finance from Boston University.

Abstract:

Drug manufacturers have recently begun submitting biosimilar applications to the Food and Drug Administration (FDA), leading many to believe that a robust U.S. biosimilar industry and substantial health savings are right around the corner. In this paper, I present an empirical assessment of the viability of biosimilars in the U.S. market and caution against such optimism given biosimilars’ considerable development costs, moderate expected market share, and diminished profit margins relative to a typical biologic. Federal regulatory burdens (biosimilar naming and clinical testing requirements), statutory burdens (State laws intended to restrict biosimilar substitution could have the effect of hindering market uptake of biosimilars) and natural market risks (payment and coverage decisions by payors) all serve as potential impediments to biosimilar market uptake in the U.S. In this paper, I present the results of a break-even analysis in which I test the economic viability of biosimilars in the United States. This analysis shows that a biosimilar manufacturer would not find it worthwhile to enter the U.S. market for most average (by sales) biologics even under favorable market conditions. Under potential regulatory and market constraints that limit biosimilar market share, only the largest biologics (average annual sales greater than $1.3 billion) are expected to attract biosimilar competition. The paper concludes that adverse decisions by policy makers and effective dissuasion by biologics manufacturers not only may impede biosimilar market share, but may stifle market entry altogether for many products.

Biography:

Dr Mohan Dewan is the principal of R K Dewan &Co, with over 40 years of experience in the field of Intellectual Property Rights.Dr Dewan is a practicing advocate and jurist. He is a registered Patent & Trademark attorney. Dr Dewan has the unique distinction of being an exceptional litigator along with being an expert in patent & trademark prosecution. Having drafted and successfully prosecuted several thousand patent specifications, he has come to be acknowledged as a specialist in patent specification drafting. Dr Dewan has obtained over 5000 patents for various Indian and foreign clients in almost every sphere of technology. His firm represents over 4000 clients worldwide.

Abstract:

The talk will cover the patenting of inventions in the field of biologics in three important jurisdictions i.e. US, Europe and India and also the distinction between inventions in biologics and inventions relating to small molecule pharmaceutical compositions. Having said this several biologics patents are said to expire in the near future and after the next few years there is potential for Biosimilars to enter the market, particularly in the field of peptides, proteins, monoclonal antibodies and vaccines. Because biologic inventions deal with living cells, the conventional notions of biosimilarity cannot be applied to inventions of this type. The importance of the cell line and the process involving the use of these cell lines in new inventions relating to biologics needs to be fully understood. The next decade is likely to see patent works in the field of biologics. The patents acts throughout the world must keep pace with this development and specialist courts will be needed to understand the intricacies of this niche science.

Biography:

Jill Myers leads CMC efforts in regulatory communications in biosimilars and novel biologics at Momenta Pharmaceuticals. Previously she built an independent consulting firm with multiple operational and strategic projects. Before that she started a process development and manufacturing department at Applied Molecular Evolution and prior to that she was a program executive at and ran the Process Biochemistry group at Biogen. Dr. Myers earned her Ph.D. in Biochemistry from UCLA and was a post-doctoral fellow at Harvard Medical School and has served on multiple industry committees including past Chair of the Board of the Recovery of Biological Products Conference Series.

Abstract:

The Biologics Price Competition and Innovation Act of 2009 created an abbreviated pathway for biological products to be biosimilar or interchangeable with an FDA-licensed product in the US. The BPCI Act and subsequent guidance from both the FDA and EU regulatory authorities has catalyzed a surge in the development of biosimilars, as well as the first biosimilar approval by the FDA in 2015. A key component to any submission is the extent to which physicochemical and biological characterization data are applied to analytical similarity. This presentation will describe the challenges in obtaining data to assure characterization of both the brand product and the biosimilar being developed and how these data can be applied during process development. Lessons learned from approved complex generics will be discussed. The choice of a broad set of analytics, both physicochemical and biological, as well as the complementary and orthogonal nature of those analytics will be described. Key characteristics that define both the brand product and the biosimilar will be discussed and will include different approaches to establish equivalence criteria as well as statistical methods which may be used to evaluate the data. The challenges such as the diversity of the brand product as well as lot age will also be addressed.

Biography:

Jenny Chen is an Associate in the biotechnology and pharmaceutical groups at the intellectual property law firm Wolf Greenfield in Boston. She focuses her practice on US and foreign patent prosecution, opinion work, due diligence and counseling clients in the areas of biological, medical, and pharmaceutical sciences. She has worked on projects related to diagnosis and treatment for various diseases and disorders, vaccine technologies, drug discovery, antibiotic biosynthesis, medical implants, gene- and cell-based therapies, pharmaceutical formulations, and herb extracts. She received her PhD from Baylor College of Medicine, specializing in molecular biology and pharmacology, and her JD from Northeastern University School of Law.

Abstract:

When it comes to clearing the path for market entry of biosimilars, there are several options available before the U.S. Patent and Trademark Office (USPTO), including post-grant reviews, inter partes reviews (IPR), and ex parte reexamination. Introduced by the America Invents Act (AIA), post-grant reviews are available within nine months after issuance of a patent filed after March 16, 2013 to any party other than the patent owner. It allows patents to be challenged on essentially any patentability basis, including patentable subject matter, prior art, and enablement/written description requirements. IPRs were also introduced by the AIA as a counterpart to post-grant reviews. IPRs can be initiated immediately after issuance of a patent filed prior to March 16, 2013 or after the nine month window for filing a post-grant review in patents filed after March 16, 2013. It allows patents to be challenged only on the basis of anticipation or obviousness, and only based on printed publications. Finally, ex parte reexamination has been available since 1981 and remains available under the AIA. Through ex parte reexamination, the patent owner or a third party may lodge a request for USPTO reexamination of an already-granted patent based on patents and printed publications that they bring to the USPTO’s attention. The requester must establish that the submitted prior art establishes a substantial and new question of patentability. For some time, patent attorneys have known the advantages of challenging patents before the USPTO through the above-noted procedures, instead of or in addition to litigation. Such advantages include (i) there is no presumption of validity in the USPTO; (ii) post-grant procedures are quicker and relatively cheaper than litigation; and (iii) discovery is much more limited. As a result, these options should be carefully considered in the lead-up to market entry.

Biography:

Milind Antani is Partner in-charge of Pharma and Life Sciences Practice at the multi-skilled, research-based international law firm, Nishith Desai Associates. He represents clients in corporate, IP and regulatory matters including corporate mergers and acquisitions, investments, regulatory and transactional matters, intellectual property prosecution and litigation, joint ventures and formation of new companies. He practiced as an ENT surgeon for 14 years prior to joining Nishith Desai Associates. He has authored and co-authored many articles, publications including two books. He has been speaking regularly at various national and international forums. He has been a visiting faculty at various institutions. He has been nominated as one of the world's leading practitioners in ‘Who's Who Legal’ for Life Sciences 2013 and 2014 in the ‘Regulatory’ section as only lawyer from India. He is also the member of the Committee of Telemedicine Society of India.

Abstract:

Biologics sector in India has seen significant growth in last few years with many players entering this sector aggressively to meet the global demands. The similar biologics are regulated in India through various acts and guidelines. The Department of Biotechnology (DBT) that comes under the Ministry of Science and Technology is the main regulatory body that is responsible for approval of ‘similar biologics’ in India. DBT operates through its Review Committee on Genetic Manipulation (RCGM) and the Central Drugs Standard Control Organization that comes under the Ministry of Health and Family Welfare). Though there are regulations that govern similar biologics, there is a need to have more robust legislation that is conducive for the industry players. The talk will explain existing legal and regulatory landscape for similar biologics in India and way to navigate through the same.

Biography:

BILL SARRAILLE is a senior member of the Healthcare Practice group and a nationally-recognized lawyer in healthcare law. Mr. Sarraille concentrates on a variety of healthcare matters, including Medicare and Medicaid reimbursement, coverage and coding, pharmaceutical price reporting, issues related to the marketing and promotion of pharmaceuticals and medical devices, internal investigations, clinical research issues, Stark and Anti-Kickback Law analyses, Medicare and Medicaid audits, healthcare acquisitions and due diligence, compliance program audits, managed care matters, healthcare contracts, administrative litigation, legislative matters, coverage for new devices and services, the representation of witnesses and companies before Congressional Committees, and the defense of healthcare criminal and False Claims Act matters.

Abstract:

The Biologics Price Competition and Innovation Act (BPCIA) was signed into law on March 23, 2010 as part of the Patient Protection and Affordable Care Act (PPACA). BPCIA’s announcement of a new Food and Drug Administration (FDA) regulatory pathway for the approval of biosimilar products has created several government pricing and reimbursement policy challenges. The proposed presentation will discuss the coverage, reimbursement, and related strategy questions from the perspective of both an experienced reimbursement counsel and a reference product manufacturer. Reimbursement issues discussed during this joint presentation will include the impact of Average Sales Price (ASP) and non-ASP reimbursement systems and the crucial distinction between the biosimilar and interchangeability standards. The potential for National Coverage Determinations, Local Coverage Determinations, and innovation reimbursement reforms will also be discussed, as will value-based contracting approaches.

Biography:

Ron Lanton is President of True North Political Solutions, LLC. Mr. Lanton has over 20 combined years of government affairs and legal experience. This includes activities on the municipal, state, and federal levels of government. Most recently he worked for a pharmaceutical wholesaler, where he created and oversaw the company’s Government Affairs Department, served as their exclusive lobbyist and also advocated for the company’s various healthcare customers. Prior to that Ron worked at a government affairs consulting firm in Arlington, VA where he worked on healthcare, energy, commerce and transportation issues. He has also clerked for a federal magistrate, was appointed as a municipal commissioner on environmental issues and has consulted Wall Street firms on financial issues. He has been a featured industry speaker on issues such as pharmaceutical safety and healthcare cost containment. Mr. Lanton has a Juris Doctor from The Ohio State University Moritz College of Law and a Bachelor of Arts from Miami University of Ohio. He is also a 40 under 40 award recipient. He has been admitted to practice law in New York, Illinois and the District of Columbia.

Abstract:

Biography:

Timothy J Shea is Director of the Biotechnology/Chemical Practice Group at Sterne, Kessler, Goldstein & Fox P.L.L.C., where he has practiced for 20 years. He specializes in advising biopharmaceutical companies and research institutions on complex legal issues relating to the protection, enforcement and transfer of their intellectual property. He practices primarily in the fields of immunology, molecular biology, genetic and medical diagnostics, biotherapeutics, and drug delivery. He has extensive experience advising clients on the creation and management of strategic patent portfolios, freedom-to-operate and patentability issues, complex prosecution strategies, validity and infringement issues, and due diligence investigations in connection with acquisitions and investments. He has published and spoken extensively on IP issues related to therapeutic antibodies and biosimilars. In addition, a significant portion of his practice involves counseling emerging companies on strategies for creating, protecting and leveraging their IP assets to grow their businesses. He received his BS in Biology from Washington and Lee University in 1988 and his JD from Chicago-Kent College of Law (with High Honors, Order of the Coif) in 1995. He served as a judicial extern to the Honorable Rebecca Pallmeyer of the U.S. District Court for the Northern District of Illinois. Prior to attending law school, he worked for several years in the biotech industry in the areas of genetic diagnostics.

Abstract:

The Biosimilar Era has arrived in the US! The past few months have seen the first ever FDA approval of a biologic deemed biosimilar to a previously approved biologic, the first cases of the Federal Circuit addressing the scope and interpretation of the US biosimilars statute, and the first patent battles between biosimilar challengers and brand companies. Against this backdrop the broad contours of the US biosimilar landscape is taking shape, and the early strategies of both brand companies and biosimilar developers are being put to the test. This session will highlight the key legal developments in the US biosimilar industry over the past year with particular focus on the patent issues. The session will also outline the strategies being implemented by biosimilar developers to gain an advantages in the critical patent disputes that are central to any biosimilar launch, as well as the strategies of brand companies in attempting hold off biosimilar competition for as long as possible. We will also discuss which of these strategies are working, and whether they are applicable only to this "first wave" of biosimilar development, or whether they will have long term applicability.

Biography:

Marcel Bassil has done major in Biochemistry at the Université de Montreal, Canada, He continued his studies (MSc and PhD) in physiology at the Université de Montreal as well as he conducted a clinical research associate program. His academic background and his professional journey in Biotechnology industries in Montreal allowed him to acquire useful and tremendous experience in cell culture and in many types of protein expression platforms with their respective bioprocesses. In 2010, he moved to Lebanon to join the academic team of the Faculty of Health Sciences at the University of Balamand as an Assistant-Professor. Later on, he joined Benta Pharma Industries as the Associate Director Biotech in charge of developing the Biotech facility and the production/characterization of several Biotech products.

Abstract:

Biosimilars are those biologics which are developed after patent expiration of innovator biopharmaceuticals. They are known as similar biologics, follow-on biologics, subsequent-entry biologics, and second-entry or off-patent biotechnology in different countries. Furthermore, they require separate marketing approval since they are not generic versions of biologics which is new in the MENA region. They establish a group of new molecules owing to a number of heterogeneities as compared to the reference innovator biologics. Moreover, this presentation will also discusses the major challenges involved in the manufacturing of Biosimilars and the required documentation on quality, safety and efficacy including comparability exercises as well as the single most important factors affecting the Biomanufacturing capacity in the region. Moreover, Biologics are one of the most important growth drivers for global pharmaceutical market but several challenges impede the way of growth of Biosimilars in the emerging markets. However, we will also take into consideration some trends that promise the bright future of Biosimilars in the MENA region. Finally, we will throw light on the regulatory guidelines of different countries especially in the MENA region and their impacts on the development of Biosimilars.

Biography:

Gary Cupit, PharmD is currently the CEO of MRC Associates, a strategy and consulting firm for private biopharmaceutical startups. Previously, he was CEO of a sleep medicine company, Somnus Therapeutics. He held similar positions at Enzo Therapeutics, publicly traded, and Sapphire Therapeutics, a private biopharmaceutical company. Prior to Sapphire, Gary was a Vice President, Global Business Development and Licensing, Novartis. Before Novartis, Gary held senior positions at Knoll Pharmaceutical as well as The Medicines Company of Cambridge, MA. He entered the industry with SmithKline Beecham Pharmaceuticals in a number of capacities in field sales, product management, and new product development where he led the launch of four products. He has more than 28 years of pharmaceutical and healthcare industry experience in addition to 14 years in university-based academics.

Abstract:

• Understand the type of FDA approval (abbreviated versus full stop BLA) impacting reimbursement • Understand how labeling will mandate the promotion of biosimilars • Understanding the differing perspectives on physician and patient perceptions of interchangeability • Understanding the challenges of pharmacovigilance and the use of Big Data to monitor safety • Understand how stakeholders at the states level can determine switching or uptake based on interpreting best practices for prescriber and patient communication • Understand lessons from the EU and their impact on the US utilization of biosimilars

Biography:

Denise M Kettelberger received her PhD from the University of Maryland School of Medicine, completed Postdoctoral studies at Baylor College of Medicine with Bert O’Malley, and moved into patent law as DNA products advanced, and joined Pravel, Gambrell as a patent agent. A former Merchant & Gould partner, she recently joined Sunstein Kann Murphy & Timbers LLP, a premier patent firm in Boston. Active in the American Intellectual Property Law Association, she is a frequent speaker on biotechnology patent issues.

Abstract:

SANDOZ filed an aBLA seeking the first approval of a U.S. biosimilar, a filgrastim product. AMGEN’s Neupogen® was the reference product. U.S. biosimilar companies closely followed progress of the first product to use the U.S. Biosimilar law (Biologics Price Control and Innovation Act. Surprisingly, SANDOZ did not proceed through the multi-step aBLA pathway of the BPCIA’s patent dispute resolution system, choosing instead to notify AMGEN of the aBLA filing, expected approval date, and intended launch. Instead of the BCPIA’s elaborate process for confidential information exchange and resolution of patent disputes, SANDOZ opted out of the process and did not provide AMGEN with its aBLA application. Because SANDOZ failed to provide its application and manufacturing process, AMGEN was entitled to sue SANDOZ for patent infringement under non-compliance sanctions provided in BCPIA steps. AMGEN sued SANDOZ for unfair competition; conversion; and infringement of AMGEN’s patents. The, District Court dismissed unfair competition and conversion clams due to its interpretation of BPCIA, finding SANDOZ did not act unlawfully. On appeal to the Federal Circuit, the BCPIA was again interpreted in Amgen v. Sandoz, decided July 21, 2015. The Court reviewed SANDOZ’s failure to comply with the first step: applicant “shall provide” its application and manufacturing process; 180 day notice of intent to market; and whether BCPIA steps are optional or mandatory. The Court found the BCPIA steps to be required when the aBLA path is chosen, but not when the applicant chooses not to use the BCPIA. Federal Circuit en banc review was requested.

Biography:

Peter Pitts is President and co-founder of the Center for Medicine in the Public Interest. Prior to founding CMPI, Pitts was a Senior Fellow for healthcare studies at the Pacific Research Institute. He has served as an adjunct professor at Indiana University’s School of Public and Environmental Affairs and Butler University.

Abstract:

Biologic drugs are extremely complex medicines. As such, unlike traditional chemical drugs, it is all but impossible for biosimilar drugs to be identical to the approved biologic they are meant to resemble. The naming of these drugs is an important patient safety issue because the INN is used in the surveillance of drugs on the market to quickly identify which drug may be responsible for an adverse event. If biosimilars use the same INN as their reference biologics, it would be more difficult for regulators to recognize exactly which product is causing a problem. As the Food and Drug Administration (FDA) finalizes its naming policy, the agency must learn from real-world global biosimilar experiences to understand how different a biosimilar can be from the original biologic. These differences will make it resoundingly clear that FDA must finalize its policy in favor of unique names. Case in point: A poster presentation at the European Crohn’s and Colitis Organization titled “Biosimilar but not the same” offered timely and real-world data on the differences between originator biologics and their biosimilars. The study examined the clinical impact of both the innovator product (Remicade) and its European Medicines Agency-approved biosimilar (Inflectra). The findings show the rates of surgery in Remicade and Inflectra groups were significantly different. Specifically, 80 percent of the Inflectra group required hospital readmission versus 5 percent of the Remicade group. The conclusion of the study is not ambiguous: “Our results suggest that biosimilars may not be as efficacious as the reference medicine.” Biosimilar approvals are based on similarity — but in the real world, success will be measured by patient outcomes. Biosimilars are here to stay and it is not surprising that physicians will have more confidence in them if they know exactly what drug they are prescribing. Distinguishable names provide that transparency and a necessary safeguard to maximize safety and credibility. It’s really that simple.

Biography:

Dr. Robert E. Zoubek is an expert in biosimilar development, manufacturing, and analytics as well as regulatory affairs. Until he joined European′s leading Consultancy Company GRC&S, he worked in several positions at Formycon (Germany) and GlycoForm (UK). As Director Scientific Affairs Robert led Formycon′s drug product development and analytical services. A focus of Formycon was its Biosimilar portfolio. In other roles he was responsible on the CMC activities of the Novel Biologics programs and led the GMP-certified Quality Control laboratories. Robert earned a PhD from the University of Erlangen-Nuremberg for his research on wound-healing peptides and he was awarded MBA from the University of Manchester. He also holds a MSc from the University of Munich. Today Robert is involved in a number of projects throughout different development stages, from early development up to marketing authorization and post-approval activities. His profound CMC knowledge and development experience make him a valuable partner for the success of projects.

Abstract:

- Rational for the analytical toolbox - Sources of information to justify your analytical strategy - The way forward: The right strategy to prove biosimilarity - Minor differences:How similar is similar enough? With increasing experience with Biosimilars also the regulator′s perspective has further evolved andn is based on a fresh scientific principle. Robert will provide the latest insights from interactions with regulators worldwide. He will present the current thinking regarding the analytical requirements of both, EMA and FDA. He will highlight the key requirements of today′s Biosimilars development and exemplify different strategies to obtain marketing approval.

Biography:

Dr. Robert E. Zoubek is an expert in biosimilar development, manufacturing, and analytics as well as regulatory affairs. Until he joined European′s leading Consultancy Company GRC&S, he worked in several positions at Formycon (Germany) and GlycoForm (UK). As Director Scientific Affairs Robert led Formycon′s drug product development and analytical services. A focus of Formycon was its Biosimilar portfolio. In other roles he was responsible on the CMC activities of the Novel Biologics programs and led the GMP-certified Quality Control laboratories. Robert earned a PhD from the University of Erlangen-Nuremberg for his research on wound-healing peptides and he was awarded MBA from the University of Manchester. He also holds a MSc from the University of Munich. Today Robert is involved in a number of projects throughout different development stages, from early development up to marketing authorization and post-approval activities. His profound CMC knowledge and development experience make him a valuable partner for the success of projects

Abstract:

The Five requirements to be fulfilled - Different strategies exemplified - How you get your strategy validated - Why companies fail European regulators have been the first to develop Biosimilar Guidance and approve in an abbreviated route products which are highly similar compared to their originator. However, with increasing experience with Biosimilars also the regulator′s perspective has further evolved enabling sponsors more flexibility in their development. Robert will provide insights into the interaction with regulators and how you should seek for validation of your development strategy. He will highlight the key requirements of today′s Biosimilars development and exemplify different strategies to obtain marketing approval in Europe.

Biography:

George Yu is the owner of the Law Offices of George C. Yu. Mr. Yu focuses his practice on intellectual property, with an emphasis on patent infringement litigation and counseling. Mr. Yu has extensive experience advising clients on matters relating to the development of biosimilars and biologics. Prior to opening his own practice, Mr. Yu was Vice President of Litigation and IP at Ariosa Diagnostics and Assistant General Counsel, Litigation at Affymetrix. Mr. Yu received his bachelor’s degree from M.I.T., his masters in biochemistry from Stanford, and his law degree from U.C.L.A.

Abstract:

The biosimilars market is expected to range from $2-20 billion or more by 2020. Yet, six years since the enactment of the Biologics Price Competition and Innovation Act (BPCIA), we are only on the cusp of the launch of the first biosimilar in the U.S., Sandoz’s Zarxio™ (filgrastim). However, the development of Zarxio™ has come with significant litigation already, particularly the fractured decision of the Court of Appeals for the Federal Circuit in Amgen v. Sandoz. Even Judge Lourie, author of the majority opinion, borrowed Winston Churchill’s phrase to describe the BPCIA: “a riddle wrapped in a mystery inside an enigma.” The CAFC’s decision in Amgen that the biosimilar developer does not have to disclose its application to the reference biologic sponsor may render the BPCIA a nullity and lead to further litigation regarding how the participates should (must?) engage in the patent dance. We will address the implication of the Amgen decision, as well as the earlier Sandoz v. Amgen litigation relating to Enbrel® (etarnercept), we will examine the patent exchange process—the so called, “patent dance”—and look to some other legal avenues where stakeholders have tried to promote or delay the entry of biosimilars to the market.

Biography:

Gregory J Glover is a registered patent attorney and non-practicing physician with the Pharmaceutical Law Group. He has experience in food and drug law, intellectual property law, and technology licensing. He has particular expertise in the patent and non-patent market exclusivity provisions of the Drug Price Competition and Patent Term Restoration Act of 1984 (“the Hatch-Waxman Act”). He received an AB, magna cum laude, in Biochemical Sciences from Harvard College in 1981 and a JD, cum laude, from Harvard Law School in 1986. Following law school, he completed medical school at Duke University in 1987, and served as an intern in Internal Medicine at New England Deaconess Hospital in Boston.

Abstract:

This presentation will describe the market exclusivity provisions that apply to biosimilars in the United States and the associated commercial implications of those provisions. The presentation will include a brief review of the market exclusivity provisions for small molecules (the Hatch-Waxman Act) and a comparison between the legal and regulatory structure for generic drugs and biosimilars.

Biography:

Patrick Lucy is the Chief Business Officer of Pfenex Inc. (NYSE: PFNX). He was a member of the team that founded Pfenex within The Dow Chemical Company. He has been in the biotechnology industry for over 22 years holding technical, operational and commercial roles throughout his career. He previously worked at The Dow Chemical Company, Collaborative BioAlliance, Lonza Biologics, Celltech Biologics and Repligen Corporation.

Abstract:

The United States biosimilars market was established based upon The Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The BPCI Act was formally passed under the Patient Protection and Affordable Care Act (ACA), and signed into law by President Barack Obama on March 23, 2010. The BPCI Act was an amendment to the Public Health Service Act (PHS Act) which created an abbreviated approval pathway known as the 351(k) pathway for biological products that are demonstrated to be highly similar (biosimilar) to a FDA approved biological product. Since March of 2010 there has been a flurry of activity in the US biosimilars market covering all aspects of the path to approval including a set of FDA guidances, 351(k) filings, and varying approaches to the “patent dance”. There has also been an emergence of biosimilar players from pure play biosimilar companies to large multinational pharmaceutical companies establishing divisions devoted to biosimilar development. This presentation will recap the evolution of the US Biosimilar market since the passage of the ACA and will explore the present and future global biosimilars opportunity.

Biography:

Patrick Lucy is the Chief Business Officer of Pfenex Inc. (NYSE: PFNX). He was a member of the team that founded Pfenex within The Dow Chemical Company. He has been in the biotechnology industry for over 22 years holding technical, operational and commercial roles throughout his career. He previously worked at The Dow Chemical Company, Collaborative BioAlliance, Lonza Biologics, Celltech Biologics and Repligen Corporation.

Abstract:

The United States biosimilars market was established based upon The Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The BPCI Act was formally passed under the Patient Protection and Affordable Care Act (ACA), and signed into law by President Barack Obama on March 23, 2010. The BPCI Act was an amendment to the Public Health Service Act (PHS Act) which created an abbreviated approval pathway known as the 351(k) pathway for biological products that are demonstrated to be highly similar (biosimilar) to a FDA approved biological product. Since March of 2010 there has been a flurry of activity in the US biosimilars market covering all aspects of the path to approval including a set of FDA guidances, 351(k) filings, and varying approaches to the “patent dance”. There has also been an emergence of biosimilar players from pure play biosimilar companies to large multinational pharmaceutical companies establishing divisions devoted to biosimilar development. This presentation will recap the evolution of the US Biosimilar market since the passage of the ACA and will explore the present and future global biosimilars opportunity.

Biography:

Sarfaraz K. Niazi, Ph.D., a leading authority on today’s biologic drug industry. Founder and Chairman of TheraProteins (TPI), a pure play biosimilar company located in Chicago, he is leveraging his diverse background and experiences to revolutionize the way biologics are made with the goal of enabling greater access to high quality, life-changing biosimilars. Niazi began his career in pharma at the University of Illinois, College of Pharmacy where he was a tenured professor before entering industry at Abbott Laboratories as Director of Technical Affairs in its international Division. Throughout his experiences, he witnessed a global disparity that fueled his passion for making high quality biologics affordable and accessible to people in need. He departed Abbott as a Volwiler Fellow to pursue that goal, first through consulting and soon thereafter through the founding of TPI.

Abstract:

Competition in the small molecule market is clearly divided into two categories, brand and generic companies. Of course, some brand companies have generic businesses and some traditional generic companies such as Teva have launched their own brand products. But for the most part, the small molecule market is comprised of brand and generic players. With the biosimilars market, we’re seeing a competitive landscape that goes beyond the traditional brand/generic paradigm. Traditional brand companies such as Pfizer, Amgen and Merck are developing biosimilars, as are major generic companies such as Sandoz, Hospira and Apotex. But all these companies have business in areas outside their biosimilars unit as well, be it in novel drug development or in generic manufacturing. Pure Play biosimilar companies have a sole focus: developing biosimilars. Since these companies did not exist prior to the creation of the biosimilars market, they face many challenges and opportunities that other established competitors are without, ranging from financing to commercilization. This presentation will explore both the risk and benefit associated with competiting in the biosimilars market as a pure play company, and provide insight into how these risks and benefits differ from those of an established generic or brand company.

Biography:

Angela Furlanetto is a Partner at Dimock Stratton LLP where she practices exclusively in the area of intellectual property litigation, particularly patent litigation with an emphasis on chemical, biochemical and pharmaceutical subject-matter. Angela has significant experience in all aspects of intellectual property litigation, ranging from pre-litigation opinions to conduct of matters through trial and appeal. She has worked with counsel in various jurisdictions to co-ordinate the Canadian part of multi-jurisdictional lawsuits.Angela is an active member of the profession, recently completing her term as Chair of the Canadian Bar Association National IP Section; she is also member of the Court Practices Committee, Federal Court Bench and Bar Committee, Fellow of the Intellectual Property Institute of Canada (IPIC), and Chair of the Harold G. Fox Intellectual Property Moot. Angela is described as "a top-drawer litigator" by IAM Patent 1000 and has been ranked for litigation since 2012. She has also been named to the International Who's Who of Life Sciences Lawyers,the International Who's Who of Patent Lawyers, Best Lawyers for intellectual property law and was ranked by Benchmark Canada as a Future Star – Ontario.

Abstract:

What’s new in Canada? New biologic approvals by Health Canada for subsequent entry biologics (SEBs) and a review of Canadian litigation involving biologics, including Canada’s first biologics decision in a patent infringement action AbbVie Corporation v. Janssen Inc., 2014 FC 55,involving the drug Stelara (ustekinumab), along with the Federal Court of Appeal decision (2014 FCA 242) to set aside the decision of the trial judge and remit the case back to the court for a new trial. The next steps and what is on the horizon for Canadian litigation.

Biography:

Ronald A Rader has been President of his own publishing/consulting company, the Biotechnology Information Institute, since late 1990. He has a BS in Microbiology, Master in Library Science, and over 30 years experience as a pharmaceutical and biotechnology information specialist, author, publisher and consultant. He is a world-class expert in biotechnology and pharmaceutical information, competitive intelligence, technology and market assessments, and information resources development; and concerning biopharmaceutical products and bioprocessing. He is best known as the author and publisher of BIOPHARMA: Biopharmaceutical Products in the U.S. and European Markets, the only information resource specializing in biopharmaceuticals. He is also the author and publisher of the Biosimilars/Biobetters Pipeline Database. For 15 years, from 1988-2003, he was the author and publisher of the Antiviral Agents Bulletin, the only periodical specializing in antiviral and HIV drug and vaccine development. Prior to his own company he served as a chemical and biomedical information specialist with companies including the Gillette, MITRE Corp. and Computer Sciences Corp.

Abstract:

The major factors that will most affect the evolution of the biosimilar markets, particularly, in the U.S. are the development pipeline and product nomenclature. There are more products, players and will be more competition than commonly presumed. As reported in the BIOPHARMA: Biosimilars/Biobetters Pipeline Database, there are now nearly 700 biosimilars and 500 biobetters in development worldwide. The market will be more like generic drugs, with many, often 10 or more, biosimilars competing with reference products and each other (along with biobetters and other new me-too products). The U.S. market will be chaotic, with many players having different goals and approaches to competing in the marketplace. The nomenclature/names to be applied to biosimilars will be the primary driver shaping their market, particularly marketing, in the U.S. The names used will control underlying perceptions of these products – whether biosimilars are each unique high-tech biopharmaceuticals or are rather generic, all much the same. The official FDA-designated non-proprietary product name to be used in marketing and labeling will determine U.S. biosimilars marketing. Generic-type names indicate products are the same and reduce or even eliminate the need for marketing, as with most generic drugs. More unique names indicate products are each different, not comparable, and require biosimilars be proactively marketed, much like innovator products. The impact of ongoing nomenclature activities by the FDA and WHO/UN, with its INN nomenclature and proposed worldwide Biological Qualifier (BQ) manufacturing site identifiers, will be discussed.

Biography:

Raymond A Huml, MS, DVM, RAC is Executive Director of Strategic Drug Development and Head of Global Biosimilars Strategic Planning for Quintiles’ Global Biosimilars Unit. He has over 25 years of experience in the clinical and biopharmaceutical industries. He has published over 50 articles and two books: One on due diligence and one on competitive intelligence. He holds an MS in Biology from East Stroudsburg University and a DVM from North Carolina State University’s College of Veterinary Medicine, and has earned the RAC (US) certification.

Abstract:

Driving the burgeoning biosimilars industry is the lucrative biologics market, worth billions, with multiple patents expiring or set to expire soon. Historically, European and Canadian regulatory authorities have taken global leadership roles in biosimilars drug development. For example, EMA published test procedures and acceptance criteria for biological products in 1999. Europe leads the pack with the most advanced and detailed biosimilar regulatory guidance - spearheading a “totality of evidence” approach - and has granted the most approvals. Other countries are moving ahead rapidly to provide cheaper copies of biologics to their citizens. The US has made significant advances towards issuing draft guidance, though it still appears that near-term, approvals will be made on a case-by-case basis. Commensurate with limited guidance and extensive innovator lobbying, the FDA has granted only one biosimilars approval – a less complex protein (filgrastim-sndz or “Zarxio” from Novartis) - in March, 2015 under the 351(k) registration pathway approved under the Biologics Price Competition and Innovation Act (BPCIA) of 2009. Further hampering progress towards US approval of a monoclonal antibody biosimilar, an FDA Advisory Committee meeting on a Remicade biosimilar from Celltrion was recently delayed. CDER recently announced that four additional biosimilar documents are set to be published in 2015. This presentation will describe the evolution of http://biosimilars-biologics.pharmaceuticalconferences.com/biosimilar development over the last 15 years, discussing key milestones leading to the first approvals in various markets. Outstanding issues will also be addressed relating to the race to identify and obtain the patients needed for global biosimilar registration trials.

Biography:

James Harris III has extensive experience within biotech, pharmaceuticals and medical devices with small start-ups, mid-sized and large firms. Mr. Harris is the founder of Healthcare Economics LLC, Co-founder of AS Biotech AG and participates on the board of directors as well as advisory boards for various firms. Prior to this he served as General Manager and Vice President at Dragon Pharmaceuticals, Inc. where he was instrumental in the launch and successful market penetration of rh-Erythropoietin (“EPO\\\\\\\") in non patented markets and is very well experienced in product licensing, business development, market access and reimbursement. Mr. Harris’s publications include “Biosimilars landscape and FDA regulatory expectations”, “Generic Drugs: World Market Outlook 2011-2021”, “Patient Empowerment and Compliance: The Role of Direct to Consumer (DTC) Advertising”, “Marketing and Globalizing Biosimilars”, “How to Establish Comparability for a faster route to Market, and “GCSF and Bioequivalence: The Emergence of Healthcare Economics”. Mr. Harris is Lead Faculty Area Chair – Financial Planning and Risk Control at the University of Phoenix West Florida Campus, has an MBA in Finance from Long Island University and participates extensively as a featured speaker at medical meetings globally.

Abstract:

The lecture will cover The presentation will cover assessing the promise and potential of biosimilars with respect to commercialization and marketing considerations to maximize market share. Recent commercial developments will also be discussed as well as provider and payer perspectives with regard to biosimilar acceptance. • Assessing the promise and potential of biosimilars • Latest progress in biosimilars development • Provider perspectives and acceptance of biosimilars • Payer perspectives and formulary acceptance

Biography:

Lisa Mueller is a partner in Michael Best’s Intellectual Property Practice Group and a Chair of the Life Sciences and Chemical Industry Group. Ms. Mueller has extensive experience in the biotechnology and pharmaceutical areas. She also has experience in evaluating, filing and securing trademarks, particularly in the pharmaceutical and life sciences area. Ms. Mueller has recently spoken at Informa’s Conference on Biosimilars and Biotech in Turkey and MENA (November 2014) as well as ACI’s Biosimilar Conference (June 2014). Ms. Mueller has written extensively about life science issues, including biosimilars

Abstract:

Biosimilars are highly-similar versions of biological drugs (biologics) approved for the treatment of a variety of disorders and diseases. Originator biologics are the most expensive drugs in the pharmaceutical industry and many cost nearly $100,000 per patient per year. As a result, biologics impose a heavy financial burden on patients and healthcare systems. While patent protection for several biologics has already expired, several other biologics are expected to lose patent protection between now and 2020. This impending patent cliff has given many biotechnology companies the opportunity to develop and market biosimilars with a cost benefit of about 20% to 30%. In order to gain a slice of the $190 billion worth of biologic’s market, many biotechnology companies have ventured into the biosimilar sector. This session will examine the key players that have ventured into this sector as well as the size and development of the market worldwide.

Biography:

Raj Davé is a partner in the Intellectual Property Group of Pillsbury Winthrop Shaw Pittman LLP – a 700 attorney law firm. He focuses on strategic intellectual property counseling, patent prosecution, dispute resolution, licensing, technology transactions, intellectual property mining and enforcement, reexamination and reissue practice, pre-litigation opinions and patent litigation. He is the author or co-author of more than 30 scientific publications and about 15 legal publications.

Abstract:

Biologics are products manufactured from living matter or manufactured in living cells using recombinant DNA biotechnologies. In Diamond v. Chakrabarty, the US Supreme Court held that a “nonnaturally occurring manufacture or composition of matter — a product of human ingenuity — having a distinctive name, character, [and] use” is patent eligible subject matter. Relying solely on the distinction between ‘product of nature’ and ‘nonnaturally occurring manufacture or composition of matter,’ currently all types of nonnaturally occurring biologics are patent eligible in the US. However, this expansive scope of patent eligibility in the US may be curtailed for patenting biologics under AIA, and the US Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc. AIA states, “No patent may issue on a claim directed to or encompassing a human organism.” Is it possible that the courts might decide that, under AIA, stem cells derived biologics fall within the scope of a human embryo? Subsequent to the passage of AIA, in Myriad, the US Supreme Court held that isolated DNA are not patent eligible, because isolated and purified human genes are indistinguishable from the products of nature, while cDNAs are patent eligible because they are synthetic DNA and are product of human ingenuity. In light of Myriad, biologics may be subject to contentions in aspect of patent eligibility, such as, are they synthetic products analogous to cDNA or mere isolation of naturally occurring products? It may be contended that isolated and purified biologics are essentially identical to naturally occurring biologics.

Biography:

Dr Fratazzi devised the concept of a Strategic Clinical Innovation Organization (SCIO) and founded the first SCIO –Boston Biotech Clinical Research (BBCR), LLC in 2009, with the objective of actively contributing to innovation in streamlining clinical research and developing strategic clinical regulatory pathways to product approval. Dr. Fratazzi has worked on several Biosimilars’ development with special attention to the major variables that impact costs. As the President of BBCR, LLC, Dr. Fratazzi acts as a consultant to biotech, pharmaceutical medical device companies, and investors on optimum clinical plan development and how to design clinical trials that reduce product development risk. She is a renowned Immunologist with over 15 years of experience in Orphan Petitions in US and EU and phase 1-4 clinical programs, contributed to the registration and approval of 4 successful products.Dr. Candida Fratazzi expertise includes Drug, Device as well as Combination Products. . Recipient of 2013, 2014 and 2015 Best Pharmaceutical Consultant, Cambridge Award, 2015 Cambridge Business Hall of Fame Award,and 2014 Top Ranked US Executives, National Council of American Executives. Act as Member of Advisory Board and Board of Directors in Life-science Technology companies. Invited speakers and chairman at international conferences. Authored over 50 scientific papers in peer review journals and several book chapters. Dr Fratazzi helps international companies to enter the US and EU markets.Dr Fratazzi received her early training in biomedical research at the Johns Hopkins University and Harvard University in the USA, and at Imperial College in London, UK.

Abstract:

Biotherapeutic products are the fastest growing medicines in the pharmaceutical market. Here we discussthe major variables that have an impact on cost and timelines of biosimilars’ development. Specifically, wereport the challenges of duplicating the innovator product results and how the dialogue on indication extrapolation has elicited new interest as the FDA compares extrapolation’s core issues. Accordingly to the WHO “it is expected that the elaboration of the data requirements and considerations for the licensing of Biosimilar products will facilitate development and worldwide access to biotherapeutics of assured quality, safety and efficacy at more affordable prices.” To address the WHO requirements, we have reviewed trial options that could assess interchangeability between the branded product and the biosimilar. Here, we discuss a case study with the objective ofassessing the immunogenicity rate between biosimilar and innovator productand evaluate the data in light of regulatory requirements. Our developed framework based on evidence-based strategies and design-centered trials highlights the factors impacting the potential cost savings in biosimilar development.

Biography:

Kerisha Bowen is a registered patent agent in Dentons’ Intellectual Property and Technology practice. She has a doctorate in organic chemistry and her practice focuses on patent prosecution in chemical and biological arts. Prior to joining Dentons, Kerisha held several assistant professorships and research positions at prestigious universities including the University of Pennsylvania and Penn State University. Kerisha was a patent analytic intern at the Union Station Technology Center where she assessed patent cost estimates of orphan drug research. She was also on the editorial staff of the Journal of Chemical and Engineering Data. As a postdoctoral fellow at the University of Pennsylvania School of Veterinary Medicine, her research focused on the P13K signaling pathway and the link between cancer and diabetes. Kerisha's doctoral research was concentrated on the synthesis of nitrogen-based pharmaceuticals from sulfinimines.

Abstract:

On March 6, 2013, Janssen Biotech, Inc. and New York University filed suit against Celltrion Healthcare Co., LTD, Celltrion, Inc,., and Hospira in the Federal District of Massachusetts. Janssen filed the suit as an attempt to assert its intellectual property rights for the drug Remicade® (Infliximab). The patents in dispute are U.S. Patent No. 6,284,471, which covers the infliximab cA2 monoclonal antibody; U.S. Patent No. 7,223, 396, which covers novel uses of infliximab to treat disease; and U.S. Patent No. 5,807,715, which covers methods of producing functional antibodies that are capable of specifically binding antigens. Celltrion submitted a Biologic License Application in August of 2014, which the FDA accepted for review in October of 2014. However, Celltrion indicated that they would begin commercial marketing of their proposed biosimilar product as early as August 5, 2015. The question at hand is was Celltrion's notice of commercial marketing premature, and how does a biosimilar company properly serve notice of commercial marketing?

Biography:

Ricardo Ibarra-Cabrera is a Biotechnology Engineer from Tecnologico de Monterrey, Mexico City. He is Industry Analyst & Editor at Mexico Health Review, an annual publication that provides a comprehensive overview of the latest developments, industry trends, business strategies, operational challenges, and legal and regulatory issues in the Mexican health industry. Ricardo is responsible for interviewing the 200 most relevant leaders of the health industry, which is the primary source of the editorial content of the 350 page publication. Ricardo is the first author of the article called “Review on the worldwide regulatoryframework for biosimilars focusing on the Mexican case as an emerging market in Latin America”, published on December 2013 in the Journal of Biotechnology Advances, which is the top 5 of all life sciences Journals today. Ricardo gave the conference “Business and Regulatory Environment of Biopharmaceuticals and Biosimilars in Latin America” in the 4th International Conference on Pharmaceutical Regulatory Affairs, Raleigh, NC, August 2014. His experience includes pharmaceutical clinical trials and consulting services to Total Quality Management for clinical studies units. He is interested in health innovation, business strategy, business intelligence, and industry analysis.

Abstract:

Biopharmaceuticals represent a very promising option for treating the most challenging diseases; nevertheless, there is no budget in the world that could effectively provide universal healthcare with a purely innovative drugs portfolio.Biosimilars represent a lower cost alternative for public healthcare systems. For instance, subsequent versions of recombinant erythropoietin with price reductions of up to 90% were launched in Mexico in 2006, and 82% cheaper rituximab versions entered the market later, among many others. Such products were originally registered as traditional generics in Mexico, but now that the regulatory framework for biosimilars is complete and well established by the Official Norm NOM-257-SSA1-2014issued in December 2014, local manufacturers face a great challenge. They need to perform some or most of the required studies for demonstrating their products’ safety, quality and biocomparability within eight months in order to renew their sanitary registration. Unfortunately, some of them cannot be fully done in Mexico due to lack of R&D infrastructure. Therefore, the biosimilars industry is at a crucial time in the country now that the Government is eager to have low-cost medicinesbut at the same time has developed more strict regulations for them. This all represents many business opportunities for laboratories, distributors and biotech companies who are willing to make quality their competitive advantage, as well as the possibility for patients to haveimproved access to safer and more efficacious treatments.

Biography:

Abe Hershkovitz founded Hershkovitz & Associates, PLLC, in Alexandria, Va. in 2003. He is a former Director of the Office of Petitions at the USPTO, where he worked for more than 27 years. Prior to working in the Office of Petitions, Mr. Hershkovitz worked as an Expert Primary Examiner. As Director of the Office of Petitions, he worked on setting policy-related USPTO guidelines. Mr. Hershkovitz specializes in petitionable matters and prosecution of Ex Parte, Inter Partes Reexamination Proceedings and CBMs. He assists clients with complex matters before the USPTO and serves as an expert witness in litigated cases. He has strong business ties with many intellectual property firms in Europe and Asia. He lectures frequently to Bar Associations and international IP organizations on various topics of patent laws and regulations and procedural tips on patent prosecution before the USPTO.

Abstract:

After enactment of the American Invents Act signed into law by President Obama effective September 16, 2012, there have been significant changes in how patentable inventions are protected and new ways of enforcing patent protection. Biomedical and computer software patents were particularly hard hit by the Supreme Court decision in Alice Corp. v. CLS Bank International and the finding that patents drawn to an abstract idea may not be enforceable. Patent invalidation through inter partes reviews and Covered Business Method challenges have become favorite vehicles over the more expensive court litigation used before. Inventors and owners of patent applications have to be far more careful when working with their patent attorneys and agents in formulating patent claims. Accused infringers and opponents of certain patents, on the other hand, need to educate themselves quickly in how to best challenge patents they believe to be unenforceable. Basic patent prosecution and very advanced reexamination practice have become more complex, and at the same time, more critical to master.

Biography:

Dr. Nigel Rulewski has 25+ years’ experience in Drug Development and Regulatory Affairs, in both large and small pharma, Venture Capital and Pharmaceutical Business Development. He is presently VP, Strategic Drug Development Group and Head, Biosimilar Center of Excellence, at Quintiles.He has planned the development of biosimilar versions of EPO, GCSF, peg-GCSF, Remicade, Humira, Enbrel, Rituximab, Avastin and Herceptin. Dr Rulewski earned his medical degree at St Bartholomew’s Medical School, University of London and also holds a Diploma in Child Health, Royal College of Physicians and a Diploma of Royal College of Obstetricians and Gynecologists

Abstract:

Biosimilars in the US are still in their infancy with only one product approved for the US market to date. However the first wave of Biosimilar products, EPO, Filgrastim, Anti TNFs and several oncology products are now well underway. The issues faced in the development of these products have evolved over time and now provide a firm basis for the next generation of biosimilar products. The issues surrounding the choice of indication in which to demonstrate biosimilarity, the basis of extrapolation and the need for transition data have all now been established. Interchangeability, a situation unique to the US approval systems still remains to be clarified, although the FDA’s likely requirements are becoming clearer. Levels of interest expressed by clinical investigators has increased significantly as the financial consequences of biosimilars become better understood. The issues encountered in the clinical development of this first wave of biosimilars and the implications of those lessons learnt for the next wave of products will be discussed.

Biography:

Currently holding the position of Chief Operating Officer & Chief Technical Officer at Bills Biotech Pvt Ltd, Vadodara,GJ (Ph. D – Molecular Microbiology - Maharaja Sayajirao University, Vadodara, M. Sc-Biotechnology- Maharaja Sayajirao University, Vadodara, Graduation B.Sc.- Zoology and Chemistry -Banaras Hindu University,Varanasi) Industrial Position Held: 1. Head of R&D & Sr. GM – Biologics and Biosimilar at Virchow Biotech Pvt Ltd, Hyderebad, 2. Head & Asst. General Manager - Biopharma operation at Microtherapeutics Research labs Pvt ltd, Chennai, 3. Sr .Manager & Head - Biosimilar and Biologics Development, Research & Training ,process consultancy at BiOZEEN, Bangalore, 4. Senior Group leader - Fermentation and Synthesis R & D at Concord Biotech Limited, 5. Senior Executive - Downstream at Intas Biopharmaceuticals Summary of Experience: More than 15 years industrial experience on process development and production of following molecules e.g. GCSF, Erythropoetin, IFN-2b, IL-2, rH-GCSF, PEG-GCSF, r-URATE OXIDASE, PEG-UOX, r-INSULIN,r-GLARGINE,r-PTH,r-EK, r-CBP, L-ASPARAGINASE,r-tPA,r-EPO,r-Protein Award Received : 1. Department of Biotechnology India fellowship Award during Post Graduation, 2. Meritorious Fellowship Award during Ph.D 3. FEMS Grant Award-2011, 4. Asian PGPR Best Research Work Award-2010, , 5. Key Note Speaker at Bioprocess India-2014,IIT-Mumbai.

Abstract:

The biologics market consists primarily of vaccines, monoclonal antibodies, recombinant proteins and diagnostics. Global pharmaceutical market projected of the growth rate 12%, Growth in biopharmaceutical market,to reach US$138 bn by 2014,dominated by products from mammalian cell cultures (>75%). Global biosimilars market ≈ $19.4 billion by 2014, growing at an expected CAGR of 89.1% from 2009 to 2014.By 2015, sales of biosimilars in US are expected US$1.9-2.6 billion, up from US$378 million in 2011.There is great opportunities in biopharmaceuticals, novel biologics & biosimilar r-proteins, Vaccines development and process parameter set up.Different scale-up criteria have been used depending on the type of fermentation and bioreactors. Growing mammalian cells in fermenters/bioreactors and to produce the protein of interest is a very cautious process and process parameters like pH or dissolved oxygen concentration need to be controlled very strictly to corroborate the consistency of a product. Minor deviations of the predefined process parameters can easily result in changes of product quality attributes like glycosylation, aggregation, c-terminal clipping or acidic variation, which can affect the pharmacokinetics of the protein e.g. case study for eryhtropoetin,Darbepoetin,Mabs etc..In reality scale-up of laboratory and pilot-plant data to commercial size industrial bioreactors is complicated.No actual data or correlation or exisiting formula is fixed for scale-up. Different people use different scale-up criteria to design commercial size bioreactor systems.In fermentation industry there are a lot of trade secrets on scale-up of bioreactors and fermentors , and very few published results.

Biography:

Tom specialises in biotech and pharmaceutical patent litigation and has been involved in some of the most significant patent cases in the UK in recent years. Conor v Angiotech and Eli Lilly v Human Genomes Sciences both went to the House of Lords/Supreme Court (the highest appeal court), while Dr Reddy v Eli Lilly only reached the Court of Appeal but is the definitive case in the law of selection patents in the UK. Tom has published many articles on patent law issues, including in the CIPA Journal (the official journal of the Chartered Institute of Patent Attorneys in the UK).

Abstract:

SPC squatting and SPCs for biologics are a hot topic in Europe following a recent slew of decisions from the courts. First, Supplementary Protection Certificates in Europe are similar to, but not quite the same as, Patent Term Extensions in the US. Tom will explore some of the differences between the two systems, and in particular Tom will examine who may apply for an SPC and on the basis of which patent. The SPC Regulation requires that the ‘product’ the subject of an SPC application must be protected by a ‘basic patent’. In the field of antibodies, is the ‘basic patent’ that patent which claims the antibody in question, or is the ‘basic patent’ that patent which claims the DNA sequence of the protein antigen, or both? Second, only one SPC is permitted per ‘product’. Tom will explore how this might apply to biologics and biosimilars – is a biosimilar the same ‘product’ as the original?

Biography:

Vivek Halan has a Postgraduate degree in biotechnology from Bharathidasan University in Trichy, Tamilnadu. He has around 10 years of research experience in downstream process development of biologics in oncology, diabetes, osteoporosis, metabolic disorder, inflammation, rheumatoid arthritis, and liver-associated diseases. He has worked for companies such as Magene Life sciences, Avesthagen Ltd., and Syngene International Ltd., where he was involved in downstream processing of various biologics, biosimilars, innovators, and a few other proteins like kinases, GPCRs, and phosphatases. Moreover, he was also involved in shake-flask protein expression in bacterial cells, mammalian cell lines, and insect cell lines. Currently, he is heading the Downstream Department at Theramyt Novobiologics.

Abstract:

Biosimilars are increasingly being developed by many companies and used as therapeutics for various diseases worldwide. There is a lot of scope to improve in biosimilar story. Biosimilar products are approved through stringent regulatory pathways in highly regulated markets such as the US, EU, Japan, Canada and Australia following loss of exclusivity of their originator reference product. The development of biosimilar product possesses various challenges such as comparable quality, safety and efficacy to a reference product in addition to other challenges in product development from laboratory to manufacturing scale. Biosimilar from process development, pre-clinical trials and clinical trials upto fill finish meets number of challenges. Quality attributes of monoclonal antibody or bio-therapeutic proteins are highly affected by both process and product related impurities. There should be an efficient upstream as well as downstream process to overcome all the bottlenecks and establishing appropriate standards for biosimilarity remains an important area for scientific, legislative and regulatory debate. I would like to give an overview on biosimilar development in various countries and current scenario. My discussion is intended for audience from biopharma industry as well as from active collaborators from various institutes and universities.

Biography:

Wolfgang Rehmann is partner of the international law firm Taylor Wessing. He counts among Germany's acknowledged experts in the field of pharmaceutical and medical law. His clients include medium-sized and international enterprises engaged in the manufacture and distribution of pharmaceutical, medicinal or medical-technological products, as well as companies acting as consultants in that area. Wolfgang Rehmann offers both advice and forensic services to leading companies of the Life Sciences industry. His forensic work is presented before German courts and also the EU courts in Luxembourg, concentrating on issues of pharmaceutical law, intellectual property, antitrust law and Community law. Wolfgang Rehmann regularly publishes specialist articles and is the author of a commentary of the German Pharmaceutical Act as well as co-author of a commentary of the German Medical Devices Act. Her regularly presents on international conferences on life sciences issues.

Abstract:

In Europe biosimilars are governed by the statutory provisions applicable for generic medicines. The legal requirements and the procedures for making an application for a marketing authorisation are set out in Directive 2001/83/EC and in Regulation (EC) No 726/2004. There are a number of possible approaches to getting approval for a biosimilar product in Europe, in particular to either submit a full dossier of pre-clinical and clinical data as would be required for any new medicinal product or to apply under the abridged procedure. An applicant for approval of a biosimilar product under the abridged procedure is required to demonstrate that its product is similar to a previously authorised product. The EMA is responsible for assessing applications from companies to market biological medicines for use in the European Union, including biosimilar medicines in case the centralised procedure is applicable. The EMA has published guidelines that govern how biosimilars are to be assessed. There are three guidelines that apply to all biosimilars: an overarching guideline which was first adopted in September 2005 and was amended in 2014, coming into effect on 30 April 2015; and two further guidelines which were both adopted by the EMA on 22 February 2006, one relating to non-clinical and clinical issues and one to quality issues. The guideline on quality issues was also amended in 2014. The presentation will give an overview to the audience about how the legal framework in the EU works and will give an update on most recent legal development within the EU in this regard.

Biography:

Christopher J Leintz, DBe, MPH, currently is the Director and Emerging Markets Strategy Lead for biosimilars at Pfizer. He received his Doctorate in Bioethics from Loyola University Chicago and his MPH from the University of Illinois at Chicago. He developed a keen interest in human rights and healthcare access from his time serving in the United States Peace Corps. He continues to pursue these interests in his current role. He has worked in the pharmaceutical industry since 2001, focusing primarily on regulatory drug development and clinical research.

Abstract:

Emerging Markets are taking on a greater level of prominence in the pharmaceutical industry. They offer true growth areas in a world where developed markets face constant pricing pressures. As a result, the level of activities in emerging markets is growing exponentially. Nowhere is this more visible than in the arena of biosimilars. Emerging markets offer the alluring promise of willing clinical trial participants and cheaper operational costs for running studies. They also tempt industry with market expansion to fuel the growth the biotech industry so keenly desires. While the benefits of bringing research and eventual MAA filings to emerging markets does have a clearly visible upside, caution must also be exercised. Whether its localization, indemnification, or cultural considerations, emerging markets must be approached in an appropriate way; a way in which industry and patients can maximize the potential of this new pharmaceutical frontier.

Biography:

Dipti Gulati completed her PhD at the age of 25 years from Allahabad University and Postdoctoral studies from Indian Institute of Sciences, India and Albert Einstein College of Medicine on Protein-Carbohydrate Interactions, USA. Currently, she is the President of PJI Biotech, a Consulting Services Organization. Previously, she held various Management Positions at Amgen, BioMerieux, Emergent Bio Solutions, Diosynth and SmithKline Beecham Pharmaceuticals. She has published more than 25 papers in reputed journals and is serving as a committee member for several interest groups of PDA.

Abstract:

A biosimilar product is a biological product that is approved based on showing that it is highly similar to an already approved biological product, known as the reference product. The biosimilar also must show it has no clinically meaningful differences in terms of safety, efficacy and quality from the reference product. A biosimilar product can only be approved by the FDA if it has the same mechanism of action, route of administration, dosage form and strength as the reference product. Omnitrope, (Somatropin) was the first product approved in the EU as a biosimilar in 2006. To date, the EMA has approved 21 biosimilar within the product classes of human growth hormone, granulocyte colony-stimulating factor, erythropoiesis stimulating agent, insulin and tumor necrosis factor (TNF)-inhibitor, for use in Europe. Two biosimilar approvals have been withdrawn; one for Filgrastim in April 2011 and one for Somatropin in May 2012, leaving a total of 19 biosimilar products approved for use in Europe. On March 6, 2015, US FDA approved Zarxio, the first biosimilar product approved in United States. Sandoz Inc.’s Zarxio is biosimilar to Amgen Inc.’s Neupogen (Filgrastim), which was originally licensed in 1991. Biosimilar’s are arelatively new emerging market. Two major growth drivers for the Biosimilar Market are Healthcare cost savings and Biologic patent expiration. The biologic products tend to have a very high price (about 20 times more than small molecule drug) and biosimilar are about a third less costly than the Originator drug and can potentially provide increased access to biologic therapies that treat life threatening cancers, anemia and immunological disease. Additionally, through 2015, about 45 Biologic drugsworth more than $60 billion in Global sales will lose Patent protection, presenting a major opportunity for the growth of the Biosimilar Market.

Biography:

Subir roy is currently leading teams to handle both marketing and medical affairs for Immunology division at Zydus Cadilla, Ahmedabad. He had worked as Senior Medical Advisor or Immunology at Bristol Myers Squibb since past 2.5 years. He was previously working as Manager, Medical Services at Glenmark Pharmaceuticals for global operations in countries like South Africa, Mauritius, Egypt, Kenya, Tanzania, Yemen, Sudan, Dubai etc., directly reporting to the Vice President.Started with MSD as HSA (Vaccines) for west zone. Specialties: Immunology, KOL management, marketing, project management, teaching, speaking in CMEs, data mining, clinical trials etc.

Abstract:

Recent data tend to suggest that immune system in Rheumatoid Arthritis (RA) might be in a state of decline and this weakened state results in demise of the tolerance mechanisms. Expansion of CD28-ve T cells is characteristically seen in RA; infact it precedes development of RA. Rising count of CD28-ve T Cells is a hallmark of immunosenecence. With successful management of RA, CD28-ve T cells count falls. Not many years ago achieving remission in rheumatoid arthritis was difficult due to lack of effective treatment. With the advent of biologics, remission is very much within reach. But biologics are expensive. And not all patients respond adequately to biologics. Hence it will be useful if we have a marker which predicts response to any disease modifying anti- rheumatic drug (DMARD), whether conventional or biologic. Newer biomarkers are constantly being looked at and CD28-ve T cells is one of them.

Biography:

Sunit Maity is highly-motivated, energetic and pro-active individual with around 6 years of Managerial experience in both upstream and downstream Development for biosimilars including recombinant protein and monoclonal antibodies, Vector development, Cell line Characterization and authentication, Assay development in well established Biotechnology industry in India. Have knowledge about Pre-clinical assay also. Has a profound knowledge and managerial experience regarding use of different model systems in drug development in Europe. He participated in a large-scale reverse genetic screen in a biotechnology industry in Germany using morpholino antisense technology in zebrafish to identify therapeutically relevant drug targets specific to tumor biology.

Abstract:

The hallmark of diabetes mellitus is hyperglycaemia resulting from impaired carbohydrate metabolism. Type 2 diabetes has a complex pathophysiology characterised by deficient insulin activity arising from decreased insulin secretion secondary to beta-cell failure, compromised insulin action in peripheral target tissues (insulin resistance), or a combination of the two abnormalities. Type 2 diabetes accounts for approximately 85% to 95% of diabetes cases in developed regions like the European Union. Age and weight are established risk factors for type 2 diabetes. The majority of patients with type 2 diabetes are overweight or obese. Byetta (Exenatide, Exendin-4) contains exenatide which is an incretin mimetic. Endogenous incretins, such as glucagon like peptide 1 (GLP-1), facilitate insulin secretion following their release from the gut into the circulation in response to food intake. Exenatide is licensed for the treatment of type 2 diabetes mellitus in combination with metformin and/or a sulfonylurea, or pioglitazone in patients who have not achieved adequate glycaemic control with these drugs alone or in combination. The increasing expenditures and cost of treatment of Byetta® highlight the absence of lower-cost generic substitutes for this drug usually referred to as biosimilars or follow-on-biologics. Biosimilars or follow-on biologics are protein-based therapeutic products that are near-identical (similar), comparable and equivalent to the branded therapeutic product. As, there is no single biosimilar developed or approved for Byetta®, we have developed the biosimilar of it using microbial route thus lowering the COGS significantly. The cell line development, process and analytical similarity data will be presented.

Biography:

Known as a pioneer of the stone-washed blue jean industry, a member of the Iowa Hawkeye NCAA Championship wrestling teams, Mark Emalfarb, CEO of Dyadic (OTCQX:DYAI) founded Dyadic in 1979. Since then, Mr. Emalfarb has successfully led and managed the evolution of Dyadic from its origins in the stone-washing business to the discovery, development, manufacturing and commercialization of specialty enzymes and other proteins, including human vaccines derived from DNA which are used in various applications to help feed, fuel and heal humankind. Mr. Emalfarb is an inventor of over 25 U.S. and foreign biotechnology patents, and is the architect behind the creation and development of Dyadic’s revolutionary patented C1 Protein Expression System,based on a recombinant Myceliopthora thermophile fungus. Mr. Emalfarb is also responsible for the formation of several strategic research, development, manufacturing and marketing relationships with U.S. and European global partners such as Sanofi Pasteur (human vaccines), BASF (food, feed and other enzymes),Abengoa (renewable non-food biofuels), and others.

Abstract:

Expression systems encompass the technologies — biological materials and associated know-how — needed to genetically modify organisms for the manufacture of recombinant proteins and other products. For Biosimilars - the future of affordable healthcare – there are many novel expression systems that offer significant improvements over the most common production hosts today (mammalian, bacterial and yeast). The new technologies are aiming to reduce theinvestments and the production and development costs in order to enable the rapid delivery of protein products into clinical development and commercialization. Biosimilar manufacturers need to develop these new technologies in order to increase expression-system yields to enable use of smaller bioreactors, reduce downstream freezer (storage) capacity and lower cost. In addition, those new technologies will also be ready to challenge the new development of personalized medicinespace. Dyadic’s Patented C1 Expression System is based on its recombinant host production organism Myceliopthorathermophila, a filamentous fungus that has been nicknamed C1. The recombinant C1 organism has demonstrated expression of much higherlevels of secreted proteins when compared to the best commercial yeast host production organisms. The C1 expression system is capable of expressing extremely high levels of secreted protein, upwards of 100 g/l, with 80% purity (or ~ 80 g/l) of a targeted heterologous protein of interest. By comparison the highest levels reported for yeast expression systems such as Pichia pastoris and Saccharomyces cerevisiae are reaching about 25% of the C1 expression levels. Dyadic is currently developing the C1 expression system to meet the Biologics and Biosimilar requirements, since this technologyhas several unique advantages over the current production host systems as:  No royalty stacking as our versatile genetic tools that enable efficient genetic manipulation and rapid selection procedure are solely owned by Dyadic.  C1’s very high productivity is expected to lead to dramatic reductions in bothfermentation and downstreamCapex, as well asOpex.  Efficient protein expression of high value proteins that include heterologous genetic sources.  The expressed protein can be secreted from the cells to the media at very high concentrations and purity, which significantly reduces the purification efficiency and cost, as well as the associated downstream freezer capacity.  C1 is proven in commercial-scale production that offers flexibility in manufacturing capacity from <1m3 up to 500 m3 fermenters.  C1 proteins are not over-glycosylated, as found in yeast, and have a structure that make the humanization of the glycosylation pattern of mammalian protein feasible.  Acquired Generally Regarded As Safe (“GRAS”) certificate recognized by the FDA. Our approach in further developing the commercially proven C1 technology for the production of therapeutic proteins in general and for Biosimilars in particular will be presented.

Biography:

Vivek K Morya has completed his PhD at the age of 29 years from DDU Gorakhpur University, Gorakhpur, India and postdoctoral studies from Inha University, Department of Biological engineering. He is an Assistant Professor in the Department of Bioengineering, at Inha University, Incheon, South Korea. He has, published more than 25 papers in reputed journals, 05 Patents, 28 Microbial Accession, and four book chapters, and has been serving as editorial board member of several journal of repute.

Abstract:

The expiring patents related to drug/pharmaceuticals and advancements in Recombinant DNA Technology (RDT) empower the mid/small-scale industries to produce pharmaceutical proteins at a large scale. These recombinant proteins are mainly expressed in E.coli, as the inclusion body. This inclusion bodies is hydrophobic and denatured lump of protein, and to recover an active protein, theoretically two steps are required, first solubilization and second refolding to achieve active protein configuration. However, most of the protein fails to achieve the 100% refolding, a common problem with heterologous protein expressed in a bacterial system. Generally, industrially purified proteins from inclusion bodies are poorly folded in respect to total protein content of purified sample. Several researchers have been carried to enhance the refolding efficacy but still striving. Among those attempted methods an Ionic Liquid (ILs) supplemented refolding process has been gained a huge attention in last decade. The ILs is molten salt (below 100oC) and regarded as green solvent for various processes. The application of ILs in protein refolding is relatively new and still in developmental phase. This present lecture is focused on application, mechanism, and experimental results with ILs based refolding buffer. In this study, Transforming growth factor beta 3 (TGF-β3) derived from E. coli host was used as refolding model protein. Refolded TGF-β3 was qualitatively analyzed via SDS-PAGE, HPLC and Fluorescence in order to calculate the refolding efficiency. The results in the present study, showed an elevated recovery of refolded protein by ILs augmented buffer, in comparison to the conventional method.

Biography:

Ines Fradi, pharmacist graduated from Faculty of Pharmacy, Monastir University. She fulfilled a specialization in hospital pharmacy in René Descartes University, Paris, France. She completed her PhD in pharmaceutical and biomedical sciences Liege University (Belgium) and Monastir University (Tunisia). She started her carrieer as hospital pharmacist in Charles Nicolle Hospital and as assistant Pofessor in analytical chemistry in the Faculty of Pharmacy of Pharmacy. She worked as assessor of Marketing Authorisation Applications in the tunisian National Laboratory of Drug Control. Actually, she is Associate Professor, Director of the Unit of the Pharmacy and Medicines, Ministry of Health, Tunisia.

Abstract:

This work deals with the tunisian experience in the redaction of guidelines on biosimilars registration and the main encountered problems. Our project started in April 2015 and we aim to accomplish the first draft before 2016. For this purpose, we established a working group composed of representatives of the competent authorities (responsibles of drug registration, quality assessment, clinical trials and pharmacovigilance) and experts in pharmacology, in analytical chemistry and in biotechnology. Delegates of the syndicate of local manufacturers (CNIP) and the tunisian syndicate of research and developement laboratories, clinical investigators and representatives of CRO biosimilar development were also involved in order to taketheir perspectives into account. Guidelines from other countries were also benchmarked. The working group was then splitted into 3 taskforces working on the quality, preclinical and clinical guidelines . In some sections, most of the guidelines are in a complete concordance. In others, many disparities were highlighted ; especially regarding interchangeability and clinical trials for some biosimilar classes. Even though the decision was made to refer to the existing guidelines in each part, many questions remained unanswered like the specific case of biosimilars manufactured in Tunisia after a technology transfer. Many other issues we were confronted to, such as the choice of the reference product when it is not registered in Tunisia and there is no access to its pharmaceutical data to assess its quality comparability.

Biography:

Abdel Halim Harrath has completed his PhD in 2005 from the University of Tunis El-Manar, Tunis, Tunisia. He is actually an Associate Professor at King Saud University, Riyadh. He has published more than 30 papers in reputed journals and is serving as an Editor-In-Chief of the Journal “Advances in reproductive Sciences”.

Abstract:

Gastric ulcers are part of a chronic relapsing disease that is well known to be a polyaetiologic chronic disease (Suleyman et al., 2001). Although many classic drugs are available to treat gastric ulcer, herbal medicines have triumphed as a diverse popular therapy and are emerging as an alternative to the available synthetic drugs (Ubaka et al., 2010). The aim of this study was to evaluate the ulceroprotective of essential oil extracted from the leaves of Juniperus. phoenicea (EOJp) against HCl/ethanol-induced ulcers in rats. The in vivo pre-treatment with EOJp at oral doses of 50, 75 and 100 mg/kg body weight has potent anti-ulcer activity, which justifies the ethnomedical claims about its significant gastroprotective effect. In fact, the pre-treatment with EOJp significantly decreased the malondialdehyde (MDA) content and increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). This effect may be related to an increase in the gastric mucosal defence mechanisms and the results of our study revealed histopathological maintaining of the integrity of the mucosa. As a result, the protective effect of the essential oil and its low toxicity requires further study to elucidate the mechanism of action and isolate the active principles. References Ubaka MC, Ukwe VC, Okoye CT, Adibe OM. Investigation into the antiulcer activity of aqueous extract of Aspilla africana. Asian. J. Medic. Sci., 2, 40–43 (2010). Suleyman H, Demirezer LO, Buyukokuroglu ME. Antiulcerogenic effect of Hippophae rhamnoides L. Phytother. Res., 625–627 (2001).

Biography:

Mr. Ronald A. Rader has been President of his own publishing/consulting company, the Biotechnology Information Institute, since late 1990. Mr. Rader has a B.S. in Microbiology, Master sin Library Science, and over 30 years experience as a pharmaceutical and biotechnology information specialist, author, publisher and consultant. He is a world-class expert in biotechnology and pharmaceutical information, competitive intelligence, technology and market assessments, and information resources development; and concerning biopharmaceutical products and bioprocessing. Mr. Rader is best known as the author and publisher of BIOPHARMA: Biopharmaceutical Products in the U.S. and European Markets (biopharma.com), the only information resource specializing in biopharmaceuticals. He has also author and publisher of the Biosimilars/Biobetters Pipeline Database (biosimilarspipeline.com). For 15 years, from 1988-200, Mr. Rader was the author and publisher of the Antiviral Agents Bulletin, the only periodical specializing in antiviral and HIV drug and vaccine development. Prior his own company he served as a chemical and biomedical information specialist with companies including the Gillette, MITRE Corp. and Computer Sciences Corp.

Abstract:

The major factors that will most affect the evolution of the biosimilar markets, particularly, in the U.S. are the development pipeline and product nomenclature. There are more products, players and will be more competitionthan commonlypresumed. As reported in the BIOPHARMA : Biosimilars/Biobetters Pipeline Database, there are now nearly 700 biosimilars and 500 biobetters in development worldwide. The market will be more like generic drugs, with many, often 10 or more, biosimilars competing with reference products and each other (along with biobetters and other new me-too products). The U.S. market will be chaotic, with many players having different goals and approaches to competing in the marketplace. The nomenclature/names to be applied to biosimilars will be the primary driver shaping their market, particularly marketing, in the U.S. The names used will control underlying perceptions of these products – whether biosimilars are each unique high-tech biopharmaceuticals or are rather generic, all much the same. The official FDA-designated non-proprietary product name to be used in marketing and labeling will determine U.S. biosimilars marketing. Generic-type names indicate products are the same and reduce or even eliminate the need for marketing, as with most generic drugs. More unique names indicate products are each different, not comparable, and require biosimilars be proactively marketed, much like innovator products. The impact of ongoing nomenclature activities by the FDA and WHO/UN, with its INN nomenclature and proposed worldwide Biological Qualifier (BQ) manufacturing site identifiers, will be discussed.

Biography:

Schauer earned a Bachelor of Science in Biochemistry and Biology and his PhD in Anaerobic Microbiology from the Virginia Polytechnic Institute, Blacksburg. Neil Schauer, PhD joins Hospira as Senior Director, Biologics Process Development. Schauer is a versatile leader and scientist with a solid background in managing large teams in the identification and development of disruptive new technologies” noted Tom Callaway, MD, Founder and President of Life Science Partner. “With his global knowledge and reach, he will serve Hospira well in its mission to become a global leader in providing biosimilar versions of the world’s most critical biological drugs.”

Abstract:

Avaxia Biologics is a clinical-stage biopharmaceutical company developing gut-targeted biobetter therapeutics. TNF is a clinically validated target in gut inflammation. Discussion will center on Avaxia’s orally-delivered, minimally absorbed anti-TNF biologic drug that acts locally in the GI tract. In contrast to first generation systemically delivered anti-TNFs, AVX-470 has low systemic exposure for greater safety, higher local concentration to drive efficacy, and the convenience of oral administration.

Biography:

Sarfaraz K. Niazi, Ph.D., a leading authority on today’s biologic drug industry. Founder and Chairman of TheraProteins (TPI), a pure play biosimilar company located in Chicago, he is leveraging his diverse background and experiences to revolutionize the way biologics are made with the goal of enablinggreater access to high quality, life-changing biosimilars. Niazi began his career in pharma at the University of Illinois, College of Pharmacy where he was a tenured professor before entering industry at Abbott Laboratories as Director of Technical Affairs in its international Division. Throughout his experiences, he witnessed a global disparity that fueled his passion for making high quality biologics affordable and accessible to people in need. He departed Abbott as a Volwiler Fellow to pursue that goal, first through consulting and soon thereafter through the founding of TPI.

Abstract:

Competition in the small molecule market is clearly divided into two categories, brand and generic companies. Of course, some brand companies have generic businesses and some traditional generic companies such as Teva have launched their own brand products. But for the most part, the small molecule market is comprised of brand and generic players. With the biosimilars market, we’re seeing a competitive landscape that goes beyond the traditional brand/generic paradigm. Traditional brand companies such as Pfizer, Amgen and Merck are developing biosimilars, as are major generic companies such as Sandoz, Hospira and Apotex. But all these companies have business in areas outside their biosimilars unit as well, be it in novel drug development or in generic manufacturing. Pure Play biosimilar companies have a sole focus: developing biosimilars. Since these companies did not exist prior to the creation of the biosimilars market, they face many challenges and opportunities that other established competitors are without, ranging from financing to commercilization. This presentation will explore both the risk and benefit associated with competiting in the biosimilars market as a pure play company, and provide insight into how these risks and benefits differ from those of an established generic or brand company.

Biography:

Abstract:

The need to characterize glycosylated biologics in terms of the compositions and specific potencies of their underlying molecular species was recognized nearly 30 years ago when the first biologics entered clinics. However, little progress in improving the characterization of glycosylated biologics has been made. It continues to be widely presumed that manufactured heterogeneous biologics can be adequately characterized by qualitative descriptions of product quality and sample average measurements of biological activity. When quantitative activity-composition studies are performed, empirical or black box methods are used, often leading to more questions than answers. Recently Zhan and Chung reported on a molecular mechanistic mathematical framework that was based on classical ligand-receptor biochemistry and was developed specifically to analyze the effects that different afucosylated IgG1 forms have on Fc-Fc gamma RIIIa binding activity. Using data published in the public domain by the Roche organization, they were able to extract valuable biochemical property information embedded in the data, thus dissecting the contributions of concentration and biochemical property differences between the different IgG1 forms to sample average activity. Such information and methods had hitherto evaded the drug development community. Their study demonstrates that computational methods provide access to important product characterization information embedded in readily generated data and thus expands the totality of evidence associated with heterogeneous IgG1s. Since the methods of Zhan and Chung are directly applicable to characterizing a variety of currently-marketed, follow-on and newly-approved IgG1s, the use of mathematical methods based on established mechanisms in ligand-receptor biochemistry should be of interest to all parties engaged in biologics research.

Biography:

Marcus Mreyen is an expert for peptide and protein analysis with a focus on mass spectrometric techniques. He holds a PhD in chemistry and spent two years in Australia were he worked in the protein analytical field at Macquarie University and the Australian Proteome Facility (APAF). Starting at Protagen in 2000 he successfully worked as a Project Manager and supported customer projects in the various protein fields. He transferred and deepen his technical understanding during a time working for Shimadzu, one of the worldwide leading analytical instrument provider, as a Product Manager for the Mass Spectrometry and Life Science products. During this time he supported customer in pharma and biotech in Europe and Russia, before returning to Protagen´s Protein Services Unit as a Director Business Development, a company serving now over 180 international clients as CRO to support the development of new protein therapeutics and biosimilars from early phases of discovery, production to GMP release testing.

Abstract:

As more and more blockbuster biologics loose patent protection, hundreds of biosimilar/ follow-on biologics developments have been started by multiple companies internationally and more will follow next years. Matching Biosimilarity is the key for these projects giving a high priority on CMC consideration with new aspects compared to NBE developments like Originator Monitoring to define the QTPP for the upcoming biosimilar and for the subsequent pool and clone selection phase. The analytical characterization and monitoring is crucial to make a quality driven development and to select the most promising candidate on top of aspects productivity, stability and upscaling possibility. Depending on the molecule complex structural characterization, glycosylation and physicochemical analysis with orthogonal techniques is required to demonstrate the biosimilarity to the originator molecule. The presentation will focus on the CMC requirements needed in the different steps of Biosimilar development. In addition different examples will highlight the analytical modules used in each development stage and how they align in a multidisciplinary overall Biosimilar development project.

Biography:

Dr. Min Zhang has over 10 years of experience in mammalian cell culture, from cell line engineering, media development, bioprocess development and biomanufacturing, bioprocess characterization, Quality-by-Design (QbD), and therapeutic protein commercialization. He is currently a Principal Scientist and Group Leader at FUJIFILM Diosynth Biotechnologies U.S.A., Inc. (FDBU) where he leads a cell culture team to support upstream process development and cGMP manufacturing for cell culture programs at various development and clinical phases. Prior to joining FDBU, Min had tenures in Cell Culture Development Department at Eli Lilly and Company and SAFC (Sigma-Aldrich). Min was a Staff Scientist and did his postdoc research at University of California at Berkeley after he received his doctorate in Molecular Cell Biology from Institute of Genetics at Fudan University.

Abstract:

In thebiosimilar journey of drug development through regulatory approval, the product quality attributes of the biosimilar protein must compare within defined limits to those of the innovator product.Unlike small molecule drugs, whose structure can usually be completely defined and entirely reproduced, biologicals are typically more complex and are almost unlikely to be shown to be structurally identical to aninnovatorproduct. Therefore, biosimilarity is generally demonstrated as having matched product quality attributes, comparablein-vitro biological activity, and no clinically meaningful differences between the biosimilar drug and innovatorproduct. The complexity of recombinant protein manufacturing processes, including expression systems (i.e. host cell line, expression vector, cell line development process), cell culture process conditions and related nutrient systems,such as cell culture media and feeds, present significant challenges to achieve the required product qualityfor biosimilars. To address these challenges, Fujifilm Diosynth Biotechnologies (FDB) has developed a systematic approach of combining media toolbox methodology and bioprocess“know-how” to screen and optimize manufacturing conditions that promote the desired product quality profilesof recombinant proteins. Case studies will be presented to highlight the efficacy of this approach and successful implementation in manufacture of biosimilar recombinant monoclonal antibodies.

Biography:

Abstract:

Streptokinase, a 414 amino acid polypeptidewithmolecularweightof 47kDa, is a potent activator of the fibrinolytic system in humans.High level expression of recombinant proteinin E.coli frequently results in accumulation of protein as in soluble aggregates known as inclusion bodies and they do offer several advantages. Expression as inclusion bodies is useful to obtain large amount of the protein, provided refolding is not difficult and recovery of the active protein is high. This is particularly true with the proteins not having disulfide bonds. Since Streptokinase does not have disulfide bonds, the focus is to obtain higher quantity of stable protein as inclusion bodies. In the present study, an attempt was made to investigate the effect of temperature and post induction time on stable (non-degradable) expression of recombinant streptokinase of highercontentas inclusion body in Escherichiacoli.

Biography:

Volker Schellenberger is President and CEO of Amunix Operating Inc., which he co-founded together with Willem Pim Stemmer in 2006. He initially served as Amunix’ Chief Scientific Officer and is the lead inventor of the company’s XTEN technology. He has over 20 years of industry experience in protein engineering and drug discovery. Prior to co-founding Amunix he served as head of Genencor’s protein engineering department where he invented combinatorial consensus mutagenesis, selection by micro-compartmentalization as well as mutator technology. He focused on the discovery and engineering of antibody-enzyme fusion proteins. Prior to his work on biotherapeutics, he led projects optimizing enzymes for industrial applications as well as microbes for metabolic pathway engineering. He received his PhD from Leipzig University(Germany) in 1986 for studies on protease catalyzed peptide synthesis. After Postdoctoral work at the Institute for Protein Research in Pushchino (Russia) he moved to the University of Göttingen where he developed a novel method for the production of peptides from recombinant peptide-multimers. After a Postdoc with Bill Rutter at the University of California, San Francisco he joined Genencor in 1994. He is author of over 40 scientific papers and inventor of more than 70 issued or pending patent applications. He is a recipient of the Karl Lohmannprize of the German Society of Biochemists.

Abstract:

PEGylation is commonly used to generate long-acting biologics (Biobetters). However, there are increasing concerns about the safety of PEG resulting from its resistance to being metabolized resulting in the accumulation in various organs including the kidney and brain. PEG is further limited by its polydispersity as well as an increasing risk of pre-exposure caused by the use of PEG in many cosmetics. Amunix has developed XTEN, a protein-based polymer that mimics the biophysical properties of PEG. XTEN is easily metabolized, thereby eliminating the risk of tissue accumulation. Proteins and peptides can be genetically fused to XTEN in a precisely controlled locations to increase biological half-life. XTEN polymers can also be produced by large scale microbial fermentation enabling chemical conjugation similar to PEGylation. XTEN has been successfully applied to a wide range of biotherapeutics and the most advanced product, human growth hormone-XTEN, VRS-317, is currently in late stage clinical testing.

Biography:

Roman joined LFB USA in 2013 where he holds position of Senior Director of Regulatory Affairs. Before joining LFB USA he was a Team Leader at the Office of Blood Research and Review of CBER FDA. His research included molecular biology, cell biology, and expression of recombinant therapeutic proteins. Before joining the FDA, he worked at Holland Laboratory of American Red Cross (ARC). Roman received his Ph.D. in Experimental Endocrinology from Polish Academy of Sciences and subsequently held positions at University of Georgia in Athens and University of Montreal.

Abstract:

Expression of recombinant proteins in the milk of transgenic dairy goats has been established asa viable and cost- effective alternative to mammalian cell culture systems. The first transgenically produced therapeutic protein, recombinant human Antithrombin (ATryn), has been approved by the European authorities in 2006 and by the FDA in. 2009. Since then it has been successfully used to treat patients with hereditary deficiency of antithrombin. Due to the high capacity of the mammary gland for protein expression and milk output, the transgenic system is particularly suitable for production of complex proteins in large quantities. This production system and large capacity for recombinant protein expression has been put to use generating monoclonal antibodies to develop several biosimilar products that will be described herein. This presentation will specifically explorethe scientific and regulatory pathwayfor the development of therapeutic monoclonal antibodies (MAb)expressed in the milk of transgenic animals under the provisions of the Biologic Price Competition and Innovation Act of 2009 (BPCI Act)

Biography:

Dr. Epstein received his BA degree from Wesleyan University, Middletown, CT and his MD/PhD degrees from the Medical Scientist Training Program at Stanford University School of Medicine under the tutelage of the late Henry Kaplan. He is currently Professor of Pathology at the USC Keck School of Medicine since 1984 and has over 160 publications and 30 patents in the field of tumor cell biology and cancer immunotherapy. He is expert in the development of novel cancer cell lines, monoclonal antibodies, antibody fusion proteins, and immunodiagnostics useful for the treatment and diagnosis of lymphomas and solid tumors.

Abstract:

Supported by a NCI SBIR contract, a biosimilar Erbitux antibody, designated ch225, has been developed over the last three years for the immunotherapy of EGFR+, KRAS mutation negative tumors. In 2011, there were 141,210 new cases of colon and rectal cancers and 49,380 deaths in the USA accounting for the 12.2 billion dollars spent on colorectal cancer treatment alone. In addition,head and neck cancers account for 45,000 additional cases that are eligible for Erbitux treatment. These statistics show that Erbitux is an important treatment modality especially since its therapeutic effects against other tumors such as non-small cell lung cancer has been demonstrated.After extensive analyses of commercial Erbitux, a biosimilar antibodywas developed using genetic engineering methods. Our initial studies demonstratedthat ch225 has the same primary amino acid sequence, charge distribution, and glycosylation profile as Erbitux required for its biosimilarity. In addition, the potencyof ch225 against EGFR positive and negative cell linesand PK/PD studies closely matched commercial Erbitux batches both in vitro and in vivo. Based upon these results, extensive cloning methods were used to develop a high yielding subclonein serum free medium which produces over 1mg/ml of antibody stable out to 35 generations. A growth supplement was also identified which increased its productivity enabling the accumulation of 4 x 107 cells/ml with over 98% viability. In conclusion, despite numerous difficulties encountered during the course of this work, a biosimilar Erbitux has been produced and readied for cGMP and clinical trials.

Biography:

Dr. Upendra Nagaich received his Ph.D. from Jiwaji University, Gwalior, India. Presently, Dr. Nagaich is working as Co-ordinator [M.Pharm], Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Noida, India. Dr. Nagaich has been conferred with several awards and honors: Award of Excellence in Pharmacy, Young Pharmacy Teacher Award, Young Performer Award, Distinguished Alumni Award. He is approved supervisor for doctoral research. Dr. Nagaich guided 23 thesis of M.Pharm. and presently guiding 03 thesis of Ph.D& 04 thesis of M.Pharm. He has filed 03 patents, published more than 50 high quality papers in international and national journals of repute, invited as speaker in various conferences.

Abstract:

Therapeutic recombinant proteins are the most significant and swiftly expanding sector of the biopharmaceutical market. The promising commerce of therapeutic proteins have remarked a standard change with enhanced efficacy, greater safety, and reduced immunogenicity approaches from the combination of clinical, scientific, technological and commercial drivers that have identified unmet needs. These proteins can be grouped into molecular types which fundamentally includes anticoagulants, blood factors, engineered protein scaffolds, enzymes, growth factors, hormones, interferons, interleukins, and thrombolytic. Recombinant proteins are manufactured in bacteria, yeast, filamentous fungi, insect cells, mammalian cells, transgenic animals, and transgenic plants. Major production of 39 percent recombinant proteins is achieved by E. coli, 35 per cent by CHO cells, 15 per cent by yeasts, 10 per cent by other mammalian systems. Recombinant Protein drugs have revolutionized the prospects for the treatment of many types of cancer and rheumatic conditions. The foremost approach which has been adopted for the production of second generation protein products comprises reformulation, pegylation and other forms of modification, or the creation of analogues with different amino acid structures. Now the long established pharmaceutical manufacturers will have to spotlight for these future biologic products. It will be a great challenge to bring about the innovation, instead of renovation, to achieve pure, safe, high efficacy, cost effective and high yielding recombinant human therapeutic proteins with excellence.