5^th European Biosimilars Congress June 27-29 , 2016 Valencia, Spain

Session Introduction

Laszlo Endrenyi

University of Toronto, Canada

Title: Interchangeability of Biological Drug Products

Time : 09:45-10:30

Biography:

Laszlo Endrenyi is Professor Emeritus of pharmacology and biostatistics in the University of Toronto. He has served the university in various positions including on its Governing Council and as Associate Dean of Graduate Studies. He sat on the Board of Directors of the American Statistical Association and the Canadian Society for Pharmaceutical Scientists; he was a president of the latter and received its Lifetime Achievement Award. Externally, he has served on grant review committees and editorial boards of research journals. He has received several recognitions, including an honorary doctorate from the Semmelweis University of Medicine. He is a Fellow of the Canadian Society for Pharmaceutical Sciences and of the American Association of Pharmaceutical Scientists. Dr. Endrenyi published a book on Kinetic Data Analysis and over 180 research papers. He has advised and widely consulted with industry and regulatory agencies.

Abstract:

Conditions for the interchangeability of biological and small-molecule drug products are very different. Small-molecule drugs are well defined and can be exactly reproduced. If their products, brand-name and generic, are declared to be bioequivalent then they are (most frequently but not always) therapeutically equivalent and can be substituted and interchanged. In contrast, biological drugs are structurally and functionally complicated, can be only imitated but not identically reproduced, are sensitive to various environmental and manufacturing conditions, are subject to biological and immunological influences. Consequently, only high similarity but not equivalence can be demonstrated, in various respects, between the marketed and new products. However, even the stated biosimilarity of two products does not enable their interchangeability in terms of switching and alternating. For this, additional conditions must be satisfied. There has been no agreement on these conditions among the various jurisdictions. Legislation in the United States, and also FDA, has set general principles. The European EMA has issued biosimilarity guidelines for several drug products. The latter permit in some cases possible interchangeability even though the issue is under the judgment of the member states. It is desirable to develop a general, scientific basis for the evaluation of interchangeability of biological drug products. Suitable study designs are considered, an approach for the assessment of switching and alternating across multiple domains is presented, and a possible criterion for the interchangeability of biological products is described.

Candida Fratazzi

BBCR Consulting, USA

Title: Evaluating Immunogenicity in Biosimilars

Time : 10:30-11:15

Biography:

Candida Fratazzi devised the concept of SCIO, cost-effective trial design, and streamlining solutions. She has been involved in the development of several bosimilars. As President of BBCR, she acts as a consultant to biotech, pharmaceutical, medical device companies, and investors. She is a renowned Immunologist and has over 15 years of experience in Orphan Drug development. She is the recipient of 2013, 2014 and 2015 Best Pharmaceutical Consultant award, Cambridge Award and ranked among the top 2014 top ranked US Executives. She helps international companies to enter the US and EU markets. She has been trained at the Johns Hopkins University, Harvard University and at Imperial College in London, UK.

Abstract:

Adoption of biosimilars is increasingly attractive to payers around the globe due to the mounting financial pressure from high expenditures on medical treatments. Clinical evaluation of comparative immunogenicity constitutes an important component of the regulatory review for biosimilar candidates. The anti-drug antibody formations are interpreted, during the review process, in relation to pharmacokinetics, pharmacodynamics, efficacy, and safety parameters. Evaluation of the immunogenicity associated with the biosimilar includes its negative impact on clinical relevant outcomes compared with the innovator product. Unwanted immunogenicity may lead to clinical consequences such as reduced or loss of efficacy, altered pharmacokinetics (PK), general immune and hypersensitivity reactions, and neutralisation of the natural counterpart (e.g. the physiological hormone). Relevant areas of discussion are: testing strategies for immunogenicity assessment; and scientific progress on the product-related factors that may contribute to the development of immunogenicity, in particular that are related to protein aggregation and post-translational modifications. For chronic administration products, immunogenicity monitoring is required for a 12-month period of continuous treatment. Furthermore, the anti-drug antibody titers (i.e., erythropoietin, growth hormone, follitropin-alfa) interpretation is influenced by product quality differences and supported by a single-dose comparative pharmacokinetic study in healthy volunteers. The acceptance margins of detected ADA incidence for the biosimilar candidate versus the innovator product have not yet been defined by EU regulators. Indeed, until now, there is no standard bioanalytical assay sensitivity adopted nor any generalization has been made on the negative influence of clinical evidence on ADA incidence. In conclusion, immunogenicity and ADA evaluation are both complex processes that start during pre-clinical comparability and continue throughout pre approval and post-approval monitoring.

Pawan Saharan

Biomix, USA

Title: Paradime shift in discovery & secretion of biosimilars via path breaking innovation

Time : 11:35-12:20

Biography:

Pawan Saharan has MS in Life Sciences (JNU); PhD in medicine (WVU) & Post Doc. (Stanford University). He has several International Publications/Presentations including in Top Scientific Journal Nature from the age of 21. He was nominated for several Global Awards including by New Drug Discovery Programme of Department of Science & Technology (GoI) funded US$ 3 million grant and the best US Scientist Award at age 22 years by AAAS, Washington DC. He has been CSO & CEO for large MNC & founder of Biomix Network Inc. USA & India.

Abstract:

Pawan Saharan invented Radha108 Nano Peptides extracted from Bovine colostrum that naturally produces biosimilar like Cytokines (Interleukin & Interferon) by secretion from Cytotoxic T- cells of the innate immune system, which was increased by 5 times by of Radha 108 Nano Peptides that get absorbed in the blood through buccal mucosa & crosses the Blood Brain Barrier. Radha 108 act on pituitary gland that in turn promotes differentiation of B cells, maturation of macrophages and monocytes & stimulates production of cytokines IL-1 to IL-11, TNF-α, INF–γ & maturation of immature thymocytes into either helper or suppressor T cells that helps building body's immune system strongly to fight any infection and immune disorders like Asthma, Allergy, URTI, Carcinomas and Type 2 diabetes saving hundreds of Billions of $ that are spent in treating such ailments with little or no efficacy. Radha 108 Nano Peptides SEQ ID 1-8 extracted from Bovine Colostrum (with the Granted US Patent No. 9,249,188 & 8,518,454 B2) consists of ELVPGVPRGTQL (DNA- binding Protein Inhibitor ID -3), VAIIQHMIKKLR (Epstein – Barr virus induced gene-2), LPQEVLNENLLRF (Alpha S1- Casein), RLNARMAELR ( S-adenosylm ethionine synthetase isoform type -1), SSLQVLNMSHN( Toll- like receptor -4), EYQELMNVK (Keratin type II cytoskeletal 59kDa component IV), VDTLNDEINFLR (Keratin type II cytoskeletal 7), DGIVNENLAER ( Ribonucleoside – diphosphate reductase small chain). Thus Radha 108 Nanopeptides stimulates the secretion of biosimilar (wide range of Cytokines like Interleukins, Interferon etc) that are very effective in treating all viral & immune disorders like HIV, Swine flu, Allergy, Asthma, Arthritis, Diarrhea, Fever, Fatigue-Malaise, Anemia, Endometriosis, cold & Flu by playing a Crucial role

Kamali Chance

Quintiles, Inc, USA

Title: FDA/EMA Current thinking on totality of evidence for biosimilar approvals

Time : 12:20-13:05

Biography:

Dr. Kamali Chance is a Vice President and Head, Global Biosimilars Regulatory Strategy, Biosimilars Center of Excellence. 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 guidance issued by European Medicines Agency (EMA) have recently undergone revisions and the FDA has issued number of revised guidelines for Quality and Scientific Considerations as well as updated Questions and Answers documents that lend much clarity. FDA has also issued draft guidelines for Nonproprietary Naming of Biological Products as well as Labeling guidelines for biosimilars. 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.

Vivek Halan

Thermyt Novobiologics Pvt. Ltd., India

Title: Biosimilars development: Overview

Biography:

Vivek Halan has a Postgraduate degree in Biotechnology from Bharathidasan University in Trichy, Tamil Nadu. He was awarded Gold Medal for securing highest aggregates in MSc Biotechnology. He has more than eleven years of research experience in downstream process development of various products in oncology, diabetes, osteoporosis, metabolic disorder, inflammation, rheumatoid arthritis and liver associated diseases. He has worked for various companies such as Magene Life sciences Pvt. Ltd., Avesthagen Ltd., and Syngene International Pvt. Ltd., where he was involved in downstream processing of various biologics, biosimilars, innovators and few other proteins such as Kinases, CD molecules as a target. He has received few R&D Star Awards for his contribution in developing various products during his tenure at Syngene. Moreover, he was also involved in recombinant protein expression in bacterial cells, monoclonal antibodies expression in mammalian cells lines in laboratory scale. He has been involved in technology transfer for various biosimilars and innovator and few molecules are in different stages of clinical trials. Currently, he is heading Downstream Process Development Department at Theramyt Novobiologics Pvt. Ltd.

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 up to 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. Cost-effective manufacturing process is a key factor to deliver a biosimilar product into the clinic and the clinical performance of biotherapeutics are highly influenced by manufacturing process. The key factors helps in reducing the cost includes the overall manufacturing process time, high titer producing cells, less number of purification steps, higher recovery and yield of clinically active product. Manufacturing process should be consistent & highly robust. The process includes modern QC & QA procedures, in-process control & process validation. Most importantly, manufacturing process should meet the same standard of originator products and the originator product should be extensively studied during the biosimilar product development. Single use technology applications should be evaluated thoroughly before initiating the uses in a manufacturing facility. The manufacturing processes should be clearly defined, controlled and validated to ensure compliance, clear records and any deviations found that should be investigated and well documented. Manufacturer comprehensively designs the production process taking all relevant guidelines into account.

Session Introduction

Andreu Soldevila

LeanBiopro, Spain

Title: Leanbioproduction of biosimilars for small to mid-size pharma companies

Time : 09:00-09:45

Biography:

Andreu Soldevila has done PhD in Biology, MsC in Biotechnology, MsC in Microbiology and Genètics, MsC in Environmental sciences, BS in Biology and BS in Biotechnology with 16 years of experience in the biotechnology and bio-pharmaceutical industry. He developed as a professional in the area of small molecules, peptides, biotherapeutics and in the last years specially in New Biological entities and Biosimilars. Professionally, he is interested in functions related to science and business (research and development, business development, technology transfer, project management) in the biotech and biopharma sectors.

Abstract:

Andreu Soldevila will present approach for Biosimilar development at Leanbiopro, providing straightforward solutions for the Lean Bioproduction of Biologics, especially Biosimilars in a Quality driven and risk based approach to minimize cost and time to market for our clients. Leanbio will provide solutions for mid-size companies, offering expression systems with freedom to operate, will emphasize in life cycle of analytical methods to support innovator drug characterization, specifications and IPC as proper control strategy and will present leanbiopro approach for life cycle in process development to support early stages of development to process characterization which will provide knowledge to support CMC for nonclinical and clinical trials in compliance with regulatory guidelines.

Fiona M Greer

SGS Life Sciences, Switzerland.

Title: Establishing “Finger-print like” biosimilarity - critical characterization steps for biosimilar assessment

Time : 09:45-10:30

Biography:

Dr Fiona Greer was a founding Director of M-Scan, contract analytical laboratories specializing in biopharmaceutical characterization. Following acquisition in 2010, she is now Global Director, Biopharma Services Development, SGS Life Sciences. Following a Ph.D. in Protein Biochemistry from Aberdeen University (1984) she joined M-Scan to establish and direct biologics characterization services. Here, she pioneered new developments in Mass Spectrometry for structural analysis and sequencing of proteins and carbohydrates resulting in numerous publications and patents. She was instrumental in expansion of the group, establishing a US facility where she was appointed VP. With over 35 years experience in glycoprotein analysis using mass spectrometry and other instrumental techniques, she has been involved with a diverse range of biotechnology products, both novel and biosimilar and consults to companies throughout the world. She is regularly invited to give presentations and workshops at international meetings and has designed and presented various technical training courses.

Abstract:

The development pathway of a biosimilar is unlike that of a novel biotherapeutic. Many regulatory authorities reference a “step-by-step” approach to establishing biosimilarity. In the early stages there is an increased requirement for ana¬lytics. This enhanced analytical effort entails physical, chemical, and biological characterization of the biosimilar in comparison to the originator reference product. Strategies at this stage must include assessment of primary and higher-order structure as well as batch-to-batch variation for both products. If found to be “similar” during this extensive characterisation, subsequent non clinical and clinical data are then required to demonstrate the same safety and efficacy profiles as the reference. The premise is that the amount of clinical data required will be less than for a novel stand-alone application. This presentation will highlight the benefit of using modern instrumental approaches to provide analytical data to support regulatory submissions. • Biosimilar development requires comprehensive physicochemical structural characterization of the (glyco)protein to demonstrate “Biosimilarity” with the originator. • Initially, batches of the target molecule are studied to determine the exact structure, post-translational modifications such as glycosylation and variability of quality attributes to establish the Quality Target Product Profile (QTTP). • Subsequently, comparative data for the biosimilar side-by-side with the originator is required. This includes both structural and functional activities. • Strategies for primary and higher order structure determination will be discussed particularly for antibodies where their size and complexity requires LC/MS/MS approaches. Appropriate orthogonal analytical techniques for “finger-print like” assessment will be reviewed.

Noelle Sunstrom

NeuClone PTY, Ltd, Australia

Title: Cell line development for the production of biosimilar monoclonal antibodies with high target bioactivity and high productivity

Biography:

Dr Sunstrom has been the CEO of NeuClone since it was established in 2007. Dr Sunstrom has over 20 years experience in the biopharmaceutical industry including more than 10 years of executive experience in biopharmaceutical companies. Dr Sunstrom has led teams in product development from bench to the market and founded and led two biotechnology companies based on CHO cell line development. Dr Sunstrom has held previous positions as CSO and Co-Founder of Acyte Biotech Pty Ltd as well as Deputy Director of both the CRC for Biopharmaceutical Research and the Bioengineering Centre at the University of New South Wales.

Abstract:

The cell line development group at NeuClone generates high quality cell lines for the production of biosimilar monoclonal antibodies (mAbs). Two characteristics are required to ensure the successful generation of a biosimilar production cell line – (1) the recombinant molecule must be expressed in sufficient quantityto ensure the project is economically viable, and (2) the molecule expressedmust behighly similar in structure and activity to the originator molecule. Traditionally the selection of cell lines expressing antibodies has been based on the selection of high producing mini-pools of cells that are subsequently further enriched for production by either limiting dilution cloning, clone-picking in semi-solid medium or by single-cell fluorescence-activated cell sorting. Clones are then expanded and evaluated in laboratory scale bioreactors to determine the best process development parameters prior to production scale up that will generate purified material for further product characterisation. The biological activity of a biosimilar mAb should mimic the originator in all aspects in order to achieve biosimilarity, including target binding and various effector functions such as signalling, cell death, proliferation, etc. We have designed a strategy that concurrently screens mini-pools and clones at an early stage for productivity as well as biosimilarity. This novel quality by design approach aims to minimise the riskof isolating high producing clones with insufficient biosimilarity early on– thus reducing the time in identifying clones with high productivity and with the right biosimilar attributes.

Reem Hamdy A Mohammed

Cairo University, Egypt

Title: Biosimilars in rheumatology practice: Where we stand?

Biography:

Reem Hamdy A Mohammed is Professor of Rheumatology and Clinical Immunology, Department of Rheumatology and Rehabilitation, Kasr Alainy School of Medicine, Cairo University. She graduated in year 1995- with excellent grades with honors, received a Master degree in Rheumatology and Rehabilitation in May 2000, PhD in Rheumatology/Clinical Immunology and MD Rheumatology and Rehabilitation in 2004. She is Fellow of the RCP, International Fellow of the American College of Rheumatology. She shared in three international book publications, has over 20 research publications in the field and is a member of the editorial board and a reviewer in a number of reputable rheumatology journals. She is devoted to serving the field of rheumatology at different levels including academic, clinical as well as research.

Abstract:

Biopharmaceuticals are biological medical products derived from cell culture or fermentation to produce therapeutic proteins that target pathogenic protein molecules by either neutralization or inhibition of their biologic hazards. Biosimilars on the other hand represent a form of biopharmaceuticals intended to be clinically equivalent end product yet unidentical to another existing biopharmaceutical. Reasons behind their being unidentical to an existing biologic are rather complex, however, many of such products are being increasingly investigated in the field of autoimmune diseases. The use of biosimilars has been linked to a 20-25% cutdown in therapeutic costs. With the increasing need for such product clinical development programs are being progressively updated to provide sufficient evidence for equivalent efficacy and comparability of safety and immunogenicity between candidate biosimilar and the reference biologic. Considering the latest therapeutic advent with the establishment of the treat to target strategy, the use of biosimilars in rheumatology practice seems tempting and deserves potential consideration with intense efforts.

Session Introduction

Nabeela Rasheed

McAndrews, Held & Malloy, Ltd, USA

Title: Dosing, double patenting and the US biosimilars landscape

Biography:

Nabeela Rasheed obtained her PhD from University of Liverpool, United Kingdom and after completing two Postdoctoral fellowships, she joined a law practice. She has been practicing in the area of Biotechnology patent law for over 20 years. As a licensed US attorney, she counsels in all areas of patent law and has particular experience in working with antibodies and other biologics. She is currently a shareholder at McAndrews, Held & Malloy.

Abstract:

The US Biosimilars landscape is developing in parallel with that of Europe. With the advent of the relatively new Inter Partes Review proceedings at the United States Patent and Trademark Office (USPTO), Biosimilar applicants are provided with a new forum to clear the path for early Biosimilar entry. Currently, the USPTO is reviewing a number of key patents that could impact the early entry of biosimilar versions several blockbuster drugs into the United States market. Key in this review are patents that claim dosing regimens and formulations. How the USPTO and the Courts view such regimens and formulations patents will be crucial in the question of early US Biosimilar entry. In parallel, obviousness-type double patenting, a once arcane judicially-created doctrine has become an extremely prominent defense against various patents in the biologics arena. This session will focus on dosing, formulations, and double patenting and the future of the biosimilar landscape. A comparison of strategies used at the USPTO with those used at the EPO also will be provided.

Session Introduction

Dipti Gulati

PJI Biotech, USA

Title: Biosimilar Development Cost: Role of Analytics

Time : 10:55-11:25

Biography:

Dipti Gulati completed her Ph.D 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 groups of PDA.

Abstract:

A biosimilar product is a biological product that is approved based on showing that it is highly similar to the reference product, with no clinically meaningful differences in terms of safety, efficacy and quality from the reference product. Biosimilar development is more time consuming and costlier that the generic development due to complex manufacturing process and product. While generics takes only couple years to develop with a cost of about 5-10 millions, biosimilar takes 8-10 years to develop with the cost of 100-300 millions. Typical steps in Biosimilar development are to characterize US licensed reference product, define target product profile, reverse engineer the biosimilar, define critical quality attributes, perform analytical comparability between proposed biosimilar and reference product, optimize the process until high analytical similarity between reference and biosimilar is achieved and address the residual uncertainties with analytical, non-clinical and clinical studies. A deep knowledge of critical quality attribute of reference and biosimilar product is the critical step for the development of biosimilar. It is important to understand how CQA links to the manufacturing process (critical process parameter and critical material attributes) and clinical performance of product (safety, efficacy and immunogenicity). A biosimilar product is not exact copy of reference product but similar to reference product. However, if biosimilar critical quality attributes are highly similar to reference product CQA, there is a great possibility that clinical performance of biosimilar will be similar to innovator product. Thorough understanding of product quality attributes can be achieved by analytical characterization and testing. The comparison between critical quality attributes can also be performed by analytical comparability studies. Analytics also allows the detection of changes in quality attributes due to change in molecule or process. There are great number of tools which can even detect minor differences in carbohydrate structures. Additionally, there are a whole array of biological assays available, which can detect if change is clinically meaningful or not. Higher analytical capability (Product Knowledge and analytical tools) is the key to reducing the development time and cost of Biosimilar.

Luis H. Camacho

Center for Oncology and Blood Disorders, USA

Title: Pharmacovigilance in Cancer Medicine

Time : 11:25-11:55

Biography:

Luis H. Camacho, MD, MPH received his MD degree from The Universidad Militar Nueva Granada in Bogota Colombia and Internal Medicine at The George Washington University in Washington DC. He subsequently trained in Medical Oncology and Hematology at Memorial Sloan-Kettering in New York. Dr Camacho has dedicated his career to clinical investigation and drug development. He has over 150 peer reviewed publications including scientific abstracts, original articles, and book chapters. Dr Camacho serves the board of several regional and National societies and committees. This year, Dr. Camacho has joined our organizing committee at Euro Biosimilars 2016.

Abstract:

Biologicals are critical in cancer medicine. Four of the top ten biological blockbusters worldwide are oncology drugs used for therapeutic or supportive care. The global market for biologic cancer therapies approximately totalled US$ 51.2 billion in 2014 and is expected to reach US$ 66.4 billion in 2019. Since the patents for most of these top-selling agents will expire by the year 2020, industry will turn to develop. In fact, manufacturing biosimilars is more cost and time effective than developing their reference products. However, the postmarketing safety monitoring is among many concerns surrounding the field of biosimilars in oncology. A PUBMED search for safety reports of the top three top cancer biologicals with upcoming patient expiration demonstrated only between two and eighteen publications since their FDA approval over one decade ago. Interestingly, while the toxicities observed during the development of bevacizumab were similar to the pre-marketing experience, a greater incidence of neutropenia was described with rituximab and a higher incidence of heart failure when in combination with adriamycin was described with the use of trastuzumab in their postmarketing vigilance. Greater efforts to educate patients and healthcare providers to report AEs as well as requesting periodical dissemination and publication of reports by sponsors will be determinant to ensure the post-marketing safety of these agents and gaining the trust of health care providers. Ultimately, the responsibility for identifying safety signals in postmarketing should be shared by healthcare providers, sponsors, and regulatory agencies in Europe and the US.

Alexander Pitters

Kaiser Optical Systems, SARL, France

Title: Process Raman Spectroscopy for In-Line Monitoring of Mammalian Cell Cultures in Real Time

Time : 11:55-12:25

Biography:

Alexander Pitters is a Life-Science Engineer (M.Sc. - University of Technology and Economics Berlin), worked at Max Planck Institute for Molecular Genetics in Berlin as a Biologic-Technical Assistant, at Procter&Gamble Brussels Innovation Centre as a Process Development Engineer, and at Bayer Technology Services in Berkeley as a PAT-Biologics Engineer. He joined Kaiser as an Applications Scientist to analyze data, create chemometric models and develop business within the pharmaceutical industry.

Abstract:

Mammalian cell cultures are complex processes where cells are cultivated under highly controlled conditions using media with a very high number of components. Current effort is focused on obtaining a better understanding of mammalian cell cultures by cultivating predominantly CHO cells for therapeutic protein production. To ensure a healthy progression of the cell culture, it is important to understand and monitor the stages of the biologic manufacturing. In order to build quality into a process a primary step is to analyze the process, understand what the critical quality attributes are, and monitor or rather control those factors. Consequently, there is a significant interest and value in techniques that provide instantaneous response for monitoring and analyzing biopharmaceutical processes. Molecular techniques - such as Raman spectroscopy - are widely used for PAT applications, because they provide in-situ information in real-time. Kaiser Raman spectroscopy is a method by which multiple bioprocess assays can be measured in situ within the bioreactor or fermenter environment. Raman is a fundamental vibrational spectroscopic technique that provides chemical and physical information that can be used to generate multi-component qualitative and quantitative predictive models. The presence of water does not interfere with the spectrum as it does with other spectroscopic methods such as NIR and mid-IR. Thus, Raman is well-suited for a host of upstream and downstream bioprocess applications. Real-time measurements within Biopharma are achieved for Glucose, Glutamine, Glutamate, Lactate, Ammonium, Viable Cell Density, Total Cell Density, Osmolality, Monoclonal Antibodies and Viability. The analyzer software enables a fully integrated bioprocess management and the instruments allow to control 4 bioreactors from a working distance of 1 to 1000 m. In recent years, Kaiser Raman has opened up new avenues to bioprocess analytics by demonstrating a technology that is robust, scaleable, provides in situ knowledge, and is transferable between cell lines, media feedstocks, and process conditions. During process development, Raman is now crucial for adopting QbD principles to define manufacturing design spaces and demonstrate holistic process and quality understanding. During production, a single Raman sensor can be used to monitor and enable control of several critical parameters in real time. Compared to traditional off-line analytical methods, in situ Raman reduces cost, consumables, sterility risk, equipment maintenance, and operator overburden. The wealth of bioprocess information enabled by in situ, real-time Raman is being realized by many companies to deploy leaner, continuous, and hybrid biopharmaceutical manufacturing. Analyzers can be used to study solids, liquids or gas without sampling accessories or preparation. Kaiser Optical Systems is the leader in Raman instrumentation and advanced holographic components for spectroscopy. Products and services are positioned in pharmaceutical and chemical manufacturing around the world.

Dipti Gulati

PJI Biotech, USA

Title: Biosimilar development cost: Role of analytics

Biography:

Dipti Gulati completed her PhD 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 groups of PDA.

Abstract:

A biosimilar product is a biological product that is approved based on showing that it is highly similar to the reference product, with no clinically meaningful differences in terms of safety, efficacy and quality from the reference product. Biosimilar development is more time consuming and costlier that the generic development due to complex manufacturing process and product. While generics takes only couple years to develop with a cost of about 5-10 millions, biosimilar takes 8-10 years to develop with the cost of 100-300 millions. Typical steps in Biosimilar development are to characterize US licensed reference product, define target product profile, reverse engineer the biosimilar, define critical quality attributes, perform analytical comparability between proposed biosimilar and reference product, optimize the process until high analytical similarity between reference and biosimilar is achieved and address the residual uncertainties with analytical, non-clinical and clinical studies. A deep knowledge of critical quality attribute of reference and biosimilar product is the critical step for the development of biosimilar. It is important to understand how CQA links to the manufacturing process (critical process parameter and critical material attributes) and clinical performance of product (safety, efficacy and immunogenicity). A biosimilar product is not exact copy of reference product but similar to reference product. However, if biosimilar critical quality attributes are highly similar to reference product CQA, there is a great possibility that clinical performance of biosimilar will be similar to innovator product. Thorough understanding of product quality attributes can be achieved by analytical characterization and testing. The comparison between critical quality attributes can also be performed by analytical comparability studies. Analytics also allows the detection of changes in quality attributes due to change in molecule or process. There are a great number of tools which can even detect minor differences in carbohydrate structures. Additionally, there is a whole array of biological assays available, which can detect if change is clinically meaningful or not. Higher analytical capability (Product Knowledge and analytical tools) is the key to reducing the development time and cost of Biosimilar.

Christina Vessely

Biologics Consulting, USA

Title: Analytical Assessment of Biosimilarity – Considerations in Study Design

Time : 12:25-12:55

Biography:

Christina Vessely, earned her Ph.D at the University of Colorado Health Sciences Center. has about 20 years experience in analytical and formulation development within the biotechnology industry. Her experience ranges from early stage research through late stage development and commercialization for small and large pharmaceutical companies. Areas of expertise include analytical method development and validation, development of reference standards, stability strategy and evaluation, and establishment of comparability and/or biosimilarity. Product experience includes vaccines, insulin analogs, cytokines, monoclonal antibodies, and other therapeutic proteins. She has been involved in the development and execution of CMC/Regulatory strategy for both novel and biosimilar products.

Abstract:

The demonstration of biosimilarity is critical to the approval of biosimilar products. While confirmatory studies may be required to confirm safety in animals and in the clinical setting, these studies are limited in their ability to assess differences between the biosimilar and the reference product. Analytical characterization has therefore become the key to the assessmet of biosimilarity. One of the most difficult aspects of the demonstration of biosimilarity is the design of the biosimilarity study. This includes the determination of how many lots of reference material must be analyzed as well as which analytical methods are required for the comparison. A strong analytical package should include release assays as well as extended characterization methods. The specific methods are dependent on the individual product. Procurement strategies for reference product must also be considered. Asessment of the reference product should be a survey of the product quality over time, as opposed to a snapshot of product quality for a single lot. Cost of the reference products can become a critical factor in procurement strategy and study design. This goal of this presentation is to provide some guidance on the design of biosimilarity studies for the analytical characterization of the biosimilar product, looking both at release characteristics as well as degradation pathway assessments.

Aparna Kasinath

Syngene International Limited

Title: Recommendations from the AAPS LBABFG Biosimilars Action Program Committee for the Validation Of Pharmacokinetic and Immunogenicity Assays in Support of Biosimilar Drug Development

Time : 14:45-15:15

Biography:

Aparna Kasinath is currently Head & Test Facility Management, Regulated Bioanalytical Laboratory, Syngene International Limited, Bangalore, India. Aparna has more than 14 years of assay experience which includes close to a decade of Immunoassay Development/Transfer, Validation and Sample analysis in support of PK and Immunogenicity studies for novel biologics and biosimilars. Aparna has a PhD from Sardar Patel University, Gujarat, India and was selected as a UNESCO fellow to the Czech Academy Of Sciences, Prague as a part of her PhD program. Aparna is an active member of various Bioanalytical Groups and works to not only to synchronize bioanalytical Practices with Global Regulatory Requirements, but also strives to bring out the Indian Bioanalytical Perspective on to a Global Platform for effective Harmonization of best practices.

Abstract:

While, the development of Biologics is complicated and a strategy driven approach, mainly owing to the complexity and nature of the molecule, development and commercialisation of a Biosimilar is two fold challenging. The Biosimilar is not only required to meet safety and efficacy end points as with all biologics, but also must demonstrate comparability with its Innovator. Demonstration of comparability requires robust developed and validated assays that are able to pick out bioanalytical differences between the Biosimilar and Innovator. Pharmacokinetic and Immunogenicity assays are the major measurement platforms for safety and efficacy data arising from non clinical and clinical studies. Currently there are no regulatory guidelines that clearly define the process/ path to be taken for designing comparability assays. This talk is aimed at discussing the recommendations made by the AAPS Ligand Binding Assay team for a harmonized strategy for Biosimilar assay development and a One or Two assay bioanalytical strategy. This discussion is tailored to all biosmilar manufacturers and biosimilar bioanalytical scientists in particular.

Rafiq Islam

Celerion Inc., USA

Title: A case study: Scientific challenges for bioanalytical method development of biosimilars

Biography:

Rafiqul Islam is the Senior Director of Bioanalytical Services at Celerion Inc. In his current role he is responsible for the scientific and operational leadership of both small and large molecule bioanalysis which includes the development, validation and execution of sample analysis to support pharmacokinetic, immunogenicity, bioequivalence and biosimilar studies. Previously, he held similar positions at EMD Millipore, Covance and Huntingdon Life Sciences. He also held several positions of increasing responsibility with Curagen Corporation. His experience and expertise includes biosimilar product research and development; bioanalytical analysis in FDA regulated environment, and streamlining workflows for laboratories with diverse operations in multiple sites. He has successfully led bioanalytical businesses over last 15 years utilizing a blend of scientific knowledge and managerial expertise in major CROs

Abstract:

According to recent FDA guidance, a Biosimilar is a biological product which is shown to be highly similar to the reference product not withstanding minor differences in clinically inactive components. It is essential to demonstrate that there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potency. Accurate and reliable bioanalytical and immunogenicity data are critical to demonstrating safety and efficacy of biosimilar and to show comparability between innovator and Biosimilar. Demonstration of comparability between biosimilar and innovator compound could be challenging due to different methods used to establish the strength of the drugs. This may lead to significantly different concentrations between biosimilar and innovator drug. Cell-based potency assays may not be able to detect differences between biosimilar and innovator due to wide acceptance ranges (70% to 130%) used in these assays. If the concentration differences cannot be resolved, it may require two assays to measure pharmacokinetic samples for innovator and biosimilar drugs. Use of two separate assays may indicate that the two products are significantly different and necessitate analysis of both compounds using both assays. Proving similarity of the immunogenicity of the biosimilar and innovator can also be quite challenging due to the fact that these types of assays are generally qualitative. The rate of immunogenicity can be particularly difficult when the incidence of positive response is low. In addition, a small process changes during the manufacturing of therapeutic proteins may lead to significant changes in the rate of immunogenicity. Due to these reasons, it is necessary to develop two robust immunogenicity assays, one for biosimilar and one for innovator, with comparable sensitivity, precision, specificity and drug tolerance. Our labs recently developed bioanalytical assays to support biosimilars of Forsteo® (also known as Forteo®). This presentation will explore above challenges and present solutions using Forsteo® assays as a case study.

Session Introduction

Sarah Cooper

National Health Service (NHS), UK

Title: Supporting biosimilar clinical trials in the UK

Time : 14:10-14:40

Biography:

Sarah Cooper is a Clinical Nutritionist by background having completed a PhD in Clinical Nutrition at the University of Sheffield, UK. She has over 12 years’ experience of delivering clinical research in a variety of settings. She joined the NIHR CRN in 2010 initially as a Operations Manager for the Specialties and is currently a Business Development Manager (Commercial)

Abstract:

The National Health Service (NHS) is a single healthcare system providing care to over 60 million people from cradle to grave, free at the point of access. The NIHR Clinical Research Network (CRN) is the research delivery arm of the NHS. It provide the world-class infrastructure that allows high-quality clinical research to take place in the NHS. The CRN turns the pledges in the government’s Strategy for UK Life Sciences into reality, by creating a better environment for conducting large scale commercial contract clinical research, so that life sciences companies can allocate clinical studies to the UK with confidence. We help researchers to set up clinical studies quickly and effectively; support the life-sciences industry to deliver their research programmes; provide health professionals with research training; and work with patients to ensure their needs are at the very centre of all research activity. We provide free support to help the life-sciences industry deliver high quality research in the NHS. Our Study Support Service provides access to dedicated research staff and support to assist with commercial contract study delivery across all therapeutic areas throughout the whole of England. It offers a flexible package of tools and services that can be shaped to meet the needs of individual companies. We work with companies to support the lifecycle of the study- from finding the right sites to deliver biosimilar clinical trials, through to support in getting the study set up within the NHS, right until end of recruitment.

Triona Bolger

Navigant Consulting, Inc., USA

Title: The emergence of orphan biosimilars

Time : 14:40-15:10

Biography:

Tríona holds a Ph.D from Kings College London and is a Senior Consultant in the Life Science Practice at Navigant Consulting with a strong interest in commercial strategy for both speciality and big pharma. She has over 4 years experience in life sciences, healthcare and consulting working in projects including stakeholder/payer mapping in an emerging market, market opportunity assessments, commercial opportunity assessment, pricing and product assessments, new product planning, market forecasting, commercial evaluation and brand planning. Tríona previously worked with Alcimed, a boutique consulting firm specialising in innovative sectors: life sciences (food, biotech, health), energy, aerospace, ICT, chemicals, aerospace & defense. Additionally, Tríona worked as a recruitment consultant with SRI Consulting, a specialist recruitment firm serving the Life Science, Consumer, Not for Profit, Climate Change and Academic sectors. Tríona holds a Ph.D in Craniofacial Developmental Biology from Kings College London and a B.A.Sc in Biochemistry from Trinity College Dublin.

Abstract:

There are $33 billion worth of annual revenue for orphan biologics that have expired or are expiring in the next 10 years, yet no biosimilars for these products have surfaced or are in late stage developement. With more clearly defined regulatory pathways for biosimilar approval recently, we address many critical questions facing originators and biosimilar makers: • Will patient identification and clinical trial recruitment pose an insurmountable hurdle for orphan biosimilars? • Will regulators entertain relaxing evidence requirements to enable biosimilar development? • Are physician and patient services a highly proprietary and costly barrier to biosimilars? • Are, or will there be, particular incentives for reimbursement of orphan biosimilars? • Is there a market size threshold for biosimilars to achieve positive commercial returns? To seek answers, we must appreciate the perspectives of four key stakeholders – regulators, payers, physicians and patients. Navigant’s financial modeling shows that orphan biologics with more than $250 million revenue will likely attract biosimilars from a profitability perspective. We are at the precipice of a new biosimilar era. Regulatory pathways have been paved; complex mAbs biosimilars like Remsima have been approved; a wave of patent expiries are sweeping across the product landscape; the first batch of biosimilars are establishing safety and credibility, providing comforting experience to physicians and patients. Investments made by major biologics companies and up starts alike will unmistakably accelerate and intensify the growth of biosimilar markets. In this context, while orphan disease presents a unique set of unknowns to biosimilar players such as the availability of clinical study subjects, KOL loyalty and payer activism, the law of pharmaceuticals will prevail in the end. Pricing strategy and payer effectiveness will be the most critical consideration in its commercial success, while a less strenuous clinical development program will make the path to market that much more favorable.

Session Introduction

Ruediger Jankowsky

Cinfa Biotech, Germany

Title: Overcoming the challenges of biosimilar development as a mid-size player

Time : 14:00-14:45

Biography:

Ruediger Jankowsky was appointed to the Managing Director of Cinfa Biotech in 2014. He is responsible for the set-up and leadership of Cinfa Biotech’s international organization. He has over 15 years of experience in the pharmaceutical industry, where he held various international executive positions in global and mid-size pharmaceutical companies. During this time he developed an expertise in medicinal product development and business development. Before joining Cinfa Biotech, he was responsible for the global management of biosimilar development projects at a leading biopharmaceutical manufacturer. He holds a PhD in protein biochemistry.

Abstract:

The market for biosimilars is evolving, rapidly. Based on the growing confidence in biosimilars, many players are entering this market, including mid-size companies. Such players with a more local focus have many opportunities in the future biosimilar market because of their strong local presence, flexibility and nimbleness. However, there are challenges regarding development costs, timelines and risk. To address these challenges, mid-size players require a clear strategy for product design, development and market launch right at the project start. In the first place, the product design has to reflect the requirements from all stakeholders. Pharmacists can provide valuable input to product design as they have a holistic view in terms of quality, usability, economics of treatment, supply chain and other aspects. Secondly, for product development, there are essential prerequisites such as robust funding, an expert team and a strong partner network. However, the development costs for biosimilars are significant and the development time up to approval exceeds five years in most cases. Hence, efficient development programs are needed without compromising quality. The biosimilar concept provides tools to make the development efficient. Accordingly, biosimilarity is established at the analytical and functional levels and confirmed by clinical studies. Thus, a thorough analytical and functional data set using state-of-the-art methods is required as well as highly specific and sensitive clinical study designs to detect clinically relevant differences. The biosimilar concept approach allows for high-quality data, and helps making development efficient, thereby supporting mid-size players to overcome the challenges of biosimilar development.

Session Introduction

Lueder Behrens

Boehmert&Boehmert, Germany

Title: The importance of IP protection and SPCs for biologics and biosimilar products

Time : 15:15-15:45

Biography:

Lueder Behrens studied biology at the University Bremen (Germany) and University of Glasgow (UK). For his diploma in virology and his PhD in field of immunology, he worked at Max-Planck-Institute for Biochemistry/Neurobiology in Martinsried/Munich. Subsequently, he was postdoctoral researcher in the field of neurovirology at the Institut Pasteur in Paris (F). In 2001, he started his training and legal studies to become a patent attorney. Since 2005 he is fully qualified patent attorney and later became a European patent attorney. He joined the renowned IP law firm Boehmert&Boehmert in 2015 and works in the offices in Berlin and Munich.

Abstract:

Research and Development nessecitates important financial investments, in particular in the pharmaceutical field, where clinicial studies costs easily hundreds of millions of Euros. Patents are important business tool to maintain exclusivity for the products provided in R&D and secure rights on the results of the underlying work. Pharmaceutical product development from lead compounds to the authorized drug easily takes more than 10 years. It is important to maintain product exclusivity in order to guarantee a satisfying return on investment. Biological products are used at increasing frequency in the pharmaceutical field, e.g. as therapeutics in the treatment of cancer and inflammatory diseases, as hormones, vaccines, etc. These products may also be subject to patent protection. It is of utmost importance for pharmaceutical companies to maintain exclusivity for a maximum period as the development and clinical testing up to market entry may be even longer than for small molecule drugs. Supplementary Protection Certificates (SPCs) provide legal means to extend protection for market authorized drugs. Recent decisions of the highest European Courts may provide guidance on the extent of protection conferred by such SPCs in the biopharmaceutical field. These decisions could provide guidance on how to protect biologicals and may influence the market entry of biosimilar products.

Paul A Calvo

Sterne, Kessler, Goldstein & Fox, USA

Title: An update on the legal landscape for biosimilars in the USA

Time : 16:15-16:45

Biography:

Paul Calvo is a Director at Sterne, Kessler, Goldstein & Fox P.L.L.C. in Washington, DC, where he spearheads the firm’s biosimilars practice. He is experienced in advising biopharmaceutical companies ranging in size from startups to industry-leading multinationals on complex legal issues related to the protection and enforcement of their intellectual property. He practices primarily in the fields of immunology and biotherapeutics, with a particular focus on therapeutic antibodies.

Abstract:

The past year has seen a great deal of activity related to the legal challenges for biosimilars in the United States. The legal landscape for biosimilars and the BPCIA is becoming clearer as decisions such as Amgen v. Sandoz are being handed down by the courts and an increasing number of biosimilar applications are being accepted by FDA. Legal challenges are also occurring at the US Patent and Trademark Office as biosimilar applicants attempt to obtain patent certainty in advance of submission of the biosimilar application to FDA. This presentation will outline the current status of the legal activity surrounding biosimilars in the US.

Christoph Volpers

Michalski Hüttermann & Partner, Germany

Title: Intellectual Property Issues in Global Biosimilar Programs

Time : 16:45-17:15

Biography:

Christoph Volpers earned a PhD in Molecular Biology from the University of Mainz, Germany, and an MBA from Bradford University, UK, both with Distinction. Chris has almost fifteen years of experience in Intellectual Property and Licensing. Before he joined the patent law firm Michalski Hüttermann & Partners, Dusseldorf/Munich, as Senior Patent Consultant in early 2015, he was Director IP Biologics of the Teva Pharmaceutical Industries/ratiopharm group for six years with global responsibility for innovative biologics and biosimilar products. He is founder of a biopharmaceutical consultancy firm, author of more than 20 publications and a member of the Licensing Executive Society.

Abstract:

In addition to development, manufacturing and commercial challenges, patent legal issues have a major impact on the success of a global biosimilar program. The multidimensional complexity of the patent landscape relating to a biosimilar candidate is due to the variety of categories of patent rights, encompassing, e.g., compound, process, formulation, indication, dosage and device patents; to the territorial diversity in scope and term of patent protection; to the technical complexity of biopharmaceutical production; and to the rapidly evolving, often controversial case law in this field. All these aspects need to be addressed when it comes to freedom-to-operate analysis and clearance of biosimilar projects, but is also relevant for securing one’s own IP position by filing and prosecuting applications on, e.g., improved process, formulation or device features. The talk will discuss challenges and chances along those lines and will give relevant examples. An update will be provided on some recent developments in patent law which will have an impact on future biologics and biosimilars patent landscapes in major markets, such as the Unitary Patent in Europe and the evolving biosimilars legislation in the US.

Nabeela Rasheed

McAndrews, Held & Malloy, Ltd, USA

Title: Dosing, Double Patenting and the US Biosimilars Landscape

Time : 17:15-17:45

Biography:

Dr. Nabeela Rasheed obtained her PhD at the age of 25 years from University of Liverpool, United Kingdom and after completing two postdoctoral fellowships, she joined a law practice. She has been practicing in the area of Biotechnology patent law for over 20 years. As a licensed US attorney, she counsels in all areas of patent law and has particular experience in working with antibodies and other biologics. She is currently a shareholder at McAndrews, Held & Malloy.

Abstract:

The US Biosimilars landscape is developing in parallel with that of Europe. With the advent of the relatively new Inter Partes Review proceedings at the United States Patent and Trademark Office (USPTO), Biosimilar applicants are provided with a new forum to clear the path for early Biosimilar entry. Currently, the USPTO is reviewing a number of key patents that could impact the early entry of biosimilar versions several blockbuster drugs into the United States market. Key in this review are patents that claim dosing regimens and formulations. How the USPTO and the Courts view such regimens and formulations patents will be crucial in the question of early US Biosimilar entry. In parallel, obviousness-type double patenting, a once arcane judicially-created doctrine has become an extremely prominent defense against various patents in the biologics arena. This session will focus on dosing, formulations, and double patenting and the future of the biosimilar landscape. A comparison of strategies used at the USPTO with those used at the EPO also will be provided.

Duu-Gong Wu

Director of Regulatory Consulting PPD, USA

Title: Regulatory Update and Overview of Specific Scientific Issues for Development and Approval of Biosimilars in US

Biography:

Duu-Gong Wu, Director of Regulatory Consulting at PPD has more than 25 years of combined US FDA and industry experience, working for 14 years at FDA as a reviewer/supervisors and 12 years as a regulatory and CMC technical consultant. He is a well-known expert in regulatory and scientific issues of biosimilar development. Prior to his works as a consultant, he worked at US FDA with the last position as Deputy Division Director of Division of New Drug Chemistry II in CDER Office of New Drug Chemistry, specializing in the review of biological products. In addition to the reviews of a large number of biotech products approved by FDA, He represented CDER as a member of ICH Expert Working Groups for both Q5E (biotech comparability) and Common Technical Document-Quality (CTD-Q) for biotech products from 1998 to 2004. Previously, he also participated in drafting ICH Q6B and Q5C guidance documents for biotechnological drug products. He served as a member of FDA Follow-on Biologic (biosimilar) Working Group, Ad Hoc Reviewer associated with USP Biotechnology Committee and the chairman of FDA CDER Follow-on Growth Hormone and Insulin Working Group responsible for setting the regulatory requirements for the approval of Omnitrope®. Currently, Dr. Wu has been assisting clients in the development of a number of MAb and therapeutic protein biosimilars at various stages with two successful IND submissions to FDA. Dr. Wu completed his Ph.D. degree in Biochemistry and Molecular Biology at University of Maryland School of Medicine and postdoctoral study at Johns Hopkins University School of Medicine, before he joined US FDA.

Abstract:

The passage of 2009 Biologics Price Competition and Innovation Act of 2009 (BPCI Act) in US established a regulatory pathway for the approval and marketing of biosimilars in US. FDA subsequently published a number of general guidance documents between 2012 and 2015 to provide guidelines to the industry on the regulatory process and clarifies the data requirements for the developments and approval of biosimilars. For the final approval of first biosimilar, Filgrastim, FDA also utilized the publication of advisory committee report to lay out the examples of regulatory and data requirements under current biosimilar law. Futhermore, the recent submission of a biosimilar application for Humira® to both EMA and US FDA also represented a milestone with far reaching implications to the field of biosimilar developments in US. Based on Dr. Wu’s unique regulatory experience at FDA and recent interactions with various regularory agencies on the development of several biosimilar Mabs and therapeutical proteins, the presentation will cover the followings: 1) An update on the current regulatory development in the US, 2) Concept of step-wide approaches in demonstratiion of comparability as recommended by FDA. 3) The unique challenges of complex regulatory and scientific issues in US such as User Fees. consultation meetings, reference products, naming, interchangeability of biosimilars. 4) Recommendations to overcome the challenges for the biosimilar product develoment in US.

Peter Bogaert

Peter Bogaert, Covington & Burling LLP, Belgium

Title: Key Regulatory and Legal Developments for Biosimilars in the EU

Biography:

Peter Bogaert is the managing partner of the Brussels office of Covington & Burling LLP where he also heads the life sciences group. He has detailed regulatory expertise under EU and national laws, handles legislative and other policy assignments and provides strategic advice. He also represents life sciences companies before the European Courts in Luxembourg and in local litigation in Belgium. Mr. Bogaert's practice covers pharmaceuticals, biotechnology, medical devices, special foods and feed, cosmetics and other consumer products and he represents numerous innovative life sciences companies, including start-ups, as well as several industry associations. Mr. Bogaert has been a member of the Brussels bar since 1984 and was called to the English bar in 1995. He holds law degrees from the University of Leuven (magna cum laude, 1982) and Oxford University (first honours, 1984).

Abstract:

The EU operates a well-established biosimilars review process that has more than a decade of experience. Almost all biosimilar applications are reviewed by the EMA, which has issued extensive guidance that covers general principles for review of biosimilars and also addresses specific aspects for various active ingredients. The practices and guidelines are also regularly updated in light of regulatory experience and international developments. Key areas of attention now are: (i) What role should the EMA play with regard to switching and interchangeability? This must be assessed also against the background of the separation of EU and national powers under the EU treaties, which provide, for instance, that the Member States have responsibility for “the organisation and delivery of health services and medical care.” (ii) What role could the EMA play in the context of HTA? Should this focus on relative efficacy or relative effectiveness and would this have an impact on biosimilars? (iii) What role can big data play for biosimilars? The regulatory approval system must also be seen in the broader context, which can have a significant impact on real use of biosimilars. This includes the INN policies of the WHO and the role of public procurement and its practical implications for switching. The talk will focus on these elements and also provide a general update on the regulatory situation in the EU. Recently, for instance, some applications for non-biotech biosimilars were made at the national level and add a new dimension to the picture.

Session Introduction

Christelle Dagoneau

Catalent Biologics, USA

Title: Impact on technology integration on better and faster biosimilars pipeline

Biography:

Christelle Dagoneau, PhD, is Director, Business Development for Catalent Pharma Solutions where she has been heavily involved in the design of biosimilar development programs for the past 5 years. Prior to joining Catalent, she served as Head of Marketing and Sales at PX'Therapeutics (France) for 6 years and has held additional commercial, marketing and research funding roles in France and in the United Kingdom between 2001 and 2005. She holds a PhD in Organic Chemistry as well as a Master in Technology & Busines Management obtained from Grenoble Business School.

Abstract:

By 2020, patents will have expired for originator biologics accounting for about $100bn and Biosimilars are expected to take over on about 25% of this market. Today, 250 companies are focusing on follow-on biologics therapies and, looking at the key players, strategic alliances are now in place and recent acquisitions have further structured this new and expanding market. Still, a swarm of new biosimilar developers plan to enter the game and will rely on stategic partnership with Biosimilar expert solution provider like Catalent to support their with innovative and virtual business models. In this talk, the author will give an overview of the standard development strategies applied to the development of biosimilar products from innovator’s characterizationn through to Phase I manufacturing stage including general timelines and budget estimates. She will also describe how the end-to-end integration of development, analytical and manufacturing activities combined with customized and high-throughput design of experiments (DOE) for cell line/process development stages can accelerate development timelines and help select better biosimilar molecules.

Candida Fratazzi

BBCR Consulting, USA

Title: Biosimilar globalization- A silver lining in untested waters

Biography:

Candida Fratazzi devised the concept of SCIO, cost-effective trial design, and streamlining solutions. She has been involved in the development of several biosimilars. As President of BBCR, she acts as a consultant to biotech, pharmaceutical, medical device companies and investors. She is a renowned Immunologist and has over 15 years of experience in Orphan Drug development. She is the recipient of 2013, 2014 and 2015 Best Pharmaceutical Consultant, Cambridge Award and 2014 top ranked US Executives. She helps international companies to enter the US and EU markets. She has had her training at the Johns Hopkins University, Harvard University and at Imperial College in London, UK.

Abstract:

Twenty-four countries have already approved biosimilars. Some of them, like China and Russia, are not WHO compliant or have developed a biosimilar specific development pathway. Biosimilar authorisation poses a number of substantial scientific and regulatory challenges for local regulatory authorities. Overall, the WHO perspective drives the similar biotherapeutic products globally. The WHO promotes a stepwise comparability exercise indicating that more work is done in pre-clinical comparability, less work is needed in clinical studies. The clinical requirements vary accordingly to existing knowledge of the reference product and the claimed therapeutic indication(s). This presentation focuses on two challenges that, in our opinion, are common across the globe. Clinical studies are necessary to demonstrate comparative efficacy. Special attention should be devoted to immunogenicity which must be always investigated for all products with due consideration to risks in different indications. Clinical Safety is to be monitored closely via risk specification and pharmacovigilance plan (PV). From a regulatory perspective, a risk management plan (RMP) or PV plan requirements do not differ in biosimilars from other biologic therapeutics. Extrapolation of safety and efficacy data is justified from one indication to another with a comprehensive comparability program with the innovator and when the target receptor and the mechanism of action are identical. We reckon it critical to discuss extrapolation of data in the context of major changes in the manufacturing process of the originator biologicals. In such situations, the clinical data and the overall information of the exercise from one indication could be allowed to other indication extrapolation.

Luis Ulloa

Rutgers – New Jersey Medical School, USA

Title: From neuronal networks to neuromodulation with biosimilars

Biography:

Dr. Ulloa completed his postdoctoral studies from Memorial Sloan Kettering Cancer Center. He is currently Associate Professor at Rutgers – New Jersey Medical School. He has published more than 75 papers in reputed journals and serves as an editorial board member of pretigious scientific journals.

Abstract:

Sepsis remains a leading cause of death in hospitalized patients, despite the efficacy of the new antibiotics and the major advances in modern hospitals. These mortality rates remain high because new antibiotics are efficient controlling the infection, but they do not control inflammation. Sepsis is one of the most lethal examples of inflammation as the overzealous systemic inflammation becomes more dangerous than the infection itself. Currently, most of the therapies are largely supportive, and there is no effective treatment for severe sepsis. We reported that electrical vagal stimulation controls inflammation and improves survival in experimental models of sepsis1,2 . But, the clinical implications of this mechanism were limited by the surgical procedure required for electrical nerve stimulation. We recently reported that neuronal stimulation with transdermal neurostimulation prevented systemic inflammation and improved survival in experimental sepsis. Neurostimulation inhibited the production of inflammatory factors by inducing the production of dopamine from the adrenal medulla. From a pharmacological perspective, dopamine inhibited macrophage’s activation via D1-like dopaminergic receptor3. Clinically, neural stimulation through neurostimulation is a promising strategy to control inflammation, but its efficacy is questioned due to the placebo effect. We also studied the effects of electroacupuncture in anesthetized patients during surgery, analyzing blood samples collected under general anesthesia to avoid any placebo effect. Electroacupuncture during surgery reduced the postoperative use of analgesics, physiological stress, hyperglycemia and inflammatory responses to trauma. These studies were funded by the NIH-GM084125.

Michael G Tovey

Ecole Normale Supérieure, France

Title: High throughput assays for the determination of the potency and comparability of biosimilars and innovator products

Biography:

Michael G Tovey, PhD, is INSERM Director of Research, Laboratory of Biotechnology, Ecole Normale Supérieure, Cachan, France. He is author of >250 articles on cytokines, biotechnology, and immunogenicity, a member of numerous scientific boards, Chair of the International Cytokines Standards Committee, a Member of the ICIS International Council, the European Adjuvant Advisory Committee, Editor-in-Chief of Detection and Quantification of Antibodies to Biopharmaceuticals, Associate Editor Cytokine, Associate Editor Journal of Interferon and Cytokine Research, Associate Editor The Scientific World Journal, a member of the Editorial Board of the Journal of Immunoassay & Immunochemistry and chair of Coral Gables Symposia.org

Abstract:

Successful development of biosimilars is dependent upon the establishment of validated and standardized assays that allow direct comparisons of the relative potency and comparability of innovator molecules and biosimilars. A validated standardized high throughput assay platform will be described in this presentation that is applicable to most biopharmaceuticals and that allows direct comparison of drug potency and comparability of innovator molecules and biosimilars in the same assay. Case studies will be presented for biopharmaceuticals ranging from novel forms of human insulin and FGF-21 to bevacizumab, trastuzumab, and structurally diverse TNF-α antagonist.

Md Abu Zafor Sadek

Renata Limited, Bangladesh

Title: Growth potential of biosimilar products in Bangladesh

Biography:

Md Abu Zafor Sadek is a Pharmacy & Business Graduate who has been successful in his 10 years career in pharmaceutical brand management & training with a high degree of creative mindset and who loves to enjoy the stretching goals. In addition to his regular job, he is pursuing for Doctor of Business Administration Degree from the Institute of Business Administration (IBA), University of Dhaka, the leading business school of the country. He has two publications in two different journals.

Abstract:

In view of the global changes in disease pattern, reduced health budget, patent expiry of some high valued products and side effects of chemical drugs, global pharmaceutical giants are concentrating on biotech products among which anticancer, cardiovascular, antidiabetic, antiasthmatic, antiarthritic products are specially important. However, developing a biotech product involved huge cost which is possible only by research based top companies. Realizing the fact, many pharmaceutical companies tried to imitate the original biotech products after patent expiry and became successful which bring a breakthrough in terms of health cost. These imitated products are termed as biosimilar products. Considering present stumpy growth in pharmaceuticals, geographical location, economic growth, drug policies, expertise etc Bangladesh may be an impressive hub for rapid growth of biosimilar products. Therefore, this study will concentrate to determine the growth potential of biosimilar products in Bangladesh.

Session Introduction

Jianguo Yang

Abpro, China

Title: Globalization Of Biosimilars

Biography:

Dr. Jianguo Yang, is the CEO of Abpro, China and Vice President Abpro, USA. He was the principal scientist , leads late stage biologics commercial projects at Genzyme/ Sanofi. Prior to Genzyme, he worked on early, late stage and commercial biologic drug development in MedImmune /Astrazeneca and Abbott labs , respectively . With over 16-year bio-pharm industry experience, and achieved world record high mammalian cell line productivity, he is an international recognized expert in biologics development, and frequently invited keynote speaker / chairperson / scientific advisor for international conferences, a member of Editor and Advisor Board for Bioprocess International Journal, reviewer for scientific and professional Journals, and authored numerous publications and patent applications. He holds both M.S. and Ph.D. degrees in molecular cell biology and biotechnology from Illinois Institute of Technology.

Abstract:

Globalization of biosimilar will come soon in the near future. China will be one of the largest biosimilar markets in the World. This presentation will articulate challenges, and opportunities and great investment potentials in China biopharma industry.

Session Introduction

Vivek Halan

Thermyt Novobiologics Pvt Ltd, India

Title: Biosimilars Development - Overview

Biography:

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 up to 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. Cost-effective manufacturing process is a key factor to deliver a biosmilar product into the clinic and the clinical performance of biotherapeutics are highly influenzed by manufacturing process. The key factors helps in reducing the cost includes the overall manufacturing process time, high titer producing cells, less number of purification steps, higher recovery and yield of cliically active product.Manufacturing process should be consistent & highly robust. The process includes modern QC & QA procedures, in-process control & process validation. Most importantly, manufacturing process should meet the same standard of originator products and the originator product should be extensively studied during the biosimilar product development. Single use technology applications should be evaluated thoroughly before initating the uses in a manufacturing facility. The manufacturing processes should be clearly defined, controlled and validated to ensure compliance, clear records, and any deviations found,that should investigated and well documented. Manufacturer comprehensively design the production process taking all relevant guidelines into account. I would like to give an overview on biosimilar development espcially the manufacturing process starting from the laboratory and current scenario. My discussion is intended for audience from biopharma industry as well as active collaborators from various institutes and universities.

Abstract:

Vivek Halan has a post graduate degree in Biotechnology from Bharathidasan University in Trichy, Tamilnadu. He was awarded Gold medal for securing highest aggregates in M.Sc Biotechnology. He has more than eleven years of research experience in Downstream Process Development of various products in Oncology, Diabetes, Osteoporosis, Metabolic Disorder, Inflammation, Rheumatoid arthritis and Liver associated diseases. He has worked for various companies such as Magene Life sciences Pvt Ltd, Avesthagen Ltd, and Syngene International Pvt Ltd where he was involved in downstream processing of various biologics, biosimilars, innovators and few other proteins such as Kinases, CD molecules as a target. He received few R &D Star awards for his contribution in developing various products during his tenure at Syngene. Moreover, he was also involved in recombinant protein expression in bacterial cells, monoclonal antibodies expression in mammalian cells lines in laboratory scale. He has been involved in technology transfer for various biosimilars and innovator and few molecules are in different stages of clinical trials. Currently, he is heading downstream process development department at Theramyt Novobiologics Pvt Ltd.