Day 2 :
Keynote Forum
Mario DiPaola,
Blue Stream Laboratories, Inc, USA
Keynote: Use of Biophysical Techniques for the Analysis of Biosimilars
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:
Biosimilars are quickly gaining position as a cornerstone of the evolving biopharmaceutical industry. Like other generics, these drug products can lower costs for life-saving therapies, but must have an efficient and well-developed characterization platform in order to deliver on economic savings. Due to the complex nature of biologics, the three dimensional structure of the protein and the higher-order structural interactions must be taken into consideration when trying to show comparability (similarity). Biophysical techniques are geared for just this type of analysis and, therefore, should be part of any biosimilars analytical characterization platform. Various biophysical techniques and their applicability to the analysis of biosimilars will be discussed during the presentation. To inform on the value that these techniques can add to a comparability program between a biosimilar product and innovator product, a case study will be presented.
Keynote Forum
Laszlo Endrenyi,
University of Toronto, Canada
Keynote: Scientific Factors in Biosimilar Product Development
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:
When the patent of a biological drug expires biosimilar products are often developed. The practice is complicated due, e.g., to the size and structure of the molecules, the complexity of the manufacturing process and the possibility of immunogenicity. The development of biosimilars calls for the consideration of several features which should be pursued in a stepwise manner and are ultimately jointly assessed based on the total available evidence. The planning and execution of the steps should rely on scientific principles. Thoughts should given, among others, to criteria for biosimilarity and interchangeability, the degree of similarity, the consistency in manufacturing processes, the assessment of quality attributes of structural and functional characterization, and the appropriate design and statistical evaluation of the investigations. The assessment of critical quality attributes for structural and functional characterization should follow the level of their relevance to the clinical outcomes. Quantitative criteria should take into account not averages but also variations. They could be either unscaled or scaled, either unweighted or weighted, either disaggregated or aggregated. A proposed biosimilarity index addresses the question of “how similar is similar” and reflects the sensitivity in the heterogeneity of variation. Quantitative indices characterize also conditions of interchangeability such as switching and alternating between drug products. Study designs should also follow these conditions. For comparative clinical studies, scientific considerations should include the choice of clinically sensitive endpoints, adequate sample size and study duration, and the appropriate design of the investigation(s).
Biography:
Oxana Iliach is a Senior Director Regulatory Affairs at the Biosimilar Center of Excellence, Quintiles. She has more than 15 year’s experience in healthcare industry, including the last 10 years in regulatory affairs at pharmaceutical and biotechnology industries.
Her expertise lies in the development of global regulatory strategy for biosimilars with the focus on overall quality and CMC compliance. She has a PhD in Pharmaceutical Science from St. Petersburg Chemical and Pharmaceutical Academy, Russia. She is a professor at Seneca College of Applied Arts and Technology, Toronto, Canada and a member of CAPRA (Canadian Association of Professionals in Regulatory Affairs) and RAPS.
Abstract:
Biosimilars is still a relatively new and rapidly developing area of biologics; as such there are ongoing changes in regulatory requirements for biosimilars in different countries across the globe. Recent changes in regulatory requirements in USA and EU have definitely attracted much attention and sparked many comments and discussions. In light of changes in these two jurisdictions, the regulatory landscape in Canada is somewhat overlooked. However, a few interesting and exciting changes in regulatory requirements for Subsequent Entry Biologics (SEBs) have occured in Canada in the last year. Examples include the revision of the guidance document “Information and Submission Requirements for Subsequent Entry Biologics (SEBs)” and the SEB Scientific Advice Meeting Pilot project.This presentation will address the following questions: Are there more differences than similarities between Health Canada, FDA and EMA regulatory requirements, and what is the future perspective?
- Brexit Effect on Biosimilars | Biosimilar Analytical Strategies | Legal Issues and BPCI Act
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 a member of PDA Regulatory and Quality Advisory Board
Abstract:
The UK decided to leave the European Union on 23 June2016, but will Brexit change Biosimilar market?
One group believes that that Brexit UK will have a significant impact on Biosimilar market in UK because UK currently don’t have a regulatory pathway to approve Biosimilars. The approval process for Biosimilars is currently carried out through a Centralized procedure with the EMA. Additionally, none of the seven Biosimilars available in UK are manufactured locally. Brexit could result in disruption of supply chain, additional importation testing, additional recertification requirements after importing, new import/export charges and uncertainty regarding regulatory strategy.Others optimistic group pinpoints that the EMA is currently headquartered in London and relocation of the headquarter to other EU country will not happen soon. Furthermore, UK may not want Drug manufacturers to follow two separate regulatory pathways for Biosimilars. It is beneficial for both UK and EU to remain part of same regulatory scheme. How Brexit will impact regulatory pathway and approval of Biosimilars, is yet to be determined. Author will present the impact of Brexit on Biosimilar market.
Dinesh Palanivelu,
Biocon Research Centre, Bangalore, India
Title: Evolution of Structure-Function paradigm in Biopharmaceutics based on Global Regulatory Needs
Biography:
Dinesh Palanivelu has completed his PhD at the age of 29 years in the field of Structural biology from Biozentrum, University of Basel, Switerland and postdoctoral studies from University of California, San Francisco, Cardiovascular Research Insitute, San Francisco U.S.A. He is the Scientific Manager - Team leader in Analytical and Molecular Characterization Division, Biocon Research Centre, Biocon Limited, Bangalore, a premier Biopharamceutical Organization in India. He has published several particles in the field of Structural biology and Protein chemistry in internationally reputed journals.
Abstract:
Protein biopharmaceuticals become a major focus in biotechnology industry for treating various life-threatening diseases. Unraveling their structural complexity represents an biggest analytical challenge. In past decade, the state-of-the-art analytical tools have been developed to dissect primary and higher order structures, PTM modifications, purity and impurity profiles and pharmacokinetic properties to provide Structure-Activity Relationship (SAR), specifically in the field of biosimilars1. Biosimilars are defined as follow-on-biologics that have been shown to have comparable quality, safety, and efficacy to the innovator products. Regulatory approval for a biosimilar version is provided on the basis of its comparability to an innovator product2. The complexity of the manufacturing process, analytical methods, structural heterogenity and the possibility of severe immunogenicity reactions makes evaluation of similarity between an innovator and the biosimilar version a great challenge for the scientific community and regulatory agencies3.
Biosimilar development involves an iterative target-directed approach, driven by thorough understanding of the structure and its biological function of a target molecule. This includes understanding batch-to-batch consistency, stability, and whether variants or aggregates can be linked to safety and efficacy4. The role of Higher-Order-Structure (HOS) has become a major investigation tool for establishing Structure-Function relationship. Differences in HOS provides potential clues to any observed biological and/or immunological differences between proteins and variant forms. What is required to integrate HOS into existing biopharmaceutical processes? Will doing so prove worth the cost, time, and effort?
Here, we present the pleothera of HOS tools designed for biosimilar programs to understand the purity and impurity profiles to establish its SAR across several orthogonal analytical methods. Extensive HOS characterization datasets adds value to the totalilty of evidence which helps the regulatory agencies in the decision making process. In summary, the paradigm shift in structure-function relationship is the current requirement for global regulatory approvals for biosimilars.
Laura Burson,
Sheppard, Mullin, Richter & Hampton LLP, USA
Title: Using IPRs In the Biosimilars Context
Biography:
Ms. Laura Burson is a partner in the Intellectual Property Practice Group in SHEPPARD, MULLIN, RICHTER & HAMPTON LLP’s Los Angeles office. She is Co-Leader of the firm's Hatch-Waxman and Biosimilars Team.
Ms. Burson focuses on intellectual property litigation with an emphasis on patent law. She is a registered patent attorney, admitted to practice before the U.S. Patent and Trademark Office. Laura has experience in all phases of litigation, including trials, arbitrations, and appeals involving intellectual property and technology-related matters. Her clients come from a broad range of technology areas, including medical devices, chemicals and chemical processes, biotechnology, pharmaceuticals, computers, and other technologies. She is also active in pro bono matters and has served a volunteer prosecutor in criminal jury trials. She currently serves on the boards of directors of LAIPLA and Center for Civic Mediation.
Abstract:
In Amgen v. Sandoz, the Federal Circuit held that biosimilar applicants are not required to provide their Biologics License Application (BLA) or engage in the patent dance – the process under the BPCIA in which the parties identify which patents the parties believe should be litigated. However, the court held that an applicant who fails to provide its BLA must provide the brand with 180-days’ notice of launch. In Amgen v. Apotex, the Federal Circuit held that a biosimilar applicant must always provide the brand with 180-days’ notice before launch, regardless of whether the applicant provided its BLA or engaged in the patent dance. The result of these decisions may be that few biosimilars applicants engage in the patent dance.
Rather than litigating biologics patents under the BPCIA, biosimilars applicants may challenge biologics patents by filing IPRs. We will review IPRs that have been filed in the biologics area, analyze key institution decisions, and provide takeaways from the institution decisions and our views on lessons that should be learned from these decisions.
Biography:
Shimada T has completed his Ph.D. at the age of 38 years from University of Tsukuba. He is the R&D manager of Life Science Research Center, SHIMADZU Corporation. His career in SHIMADZU is from 2001, and has been participated in several project such as age-related liver proteomics, next generation mass spectrometry, collaboration with National Cancer Center Japan, and academic careers in several university. He has published more than 20 papers in scientific journals. His specialities are protein chemistry, proteomics, and bioanalysis by mass spectrometry.
Abstract:
Monoclonal antibodies have become a major therapeutic strategy in cancer care. The approved antibody drugs have been about 41 items, and many clinical trials including biosimilars have been now performing in the world. For precision medicine, pharmacokinetic (PK) information in blood or disease tissue will become one of the good indicators for drug efficacy. Therefore, versatile analysis for the direct detection of antibody drugs will be desired. The LCMS bioanalysis of antibody drugs is a significant platform for the selective quantitation of antibody specific region or the feasibility of multiplex assays. For a regulated LCMS bioanalysis independent of a variety of monoclonal antibodies or biological taxonomy sources, we have focused on the two features: antibody structure-indicated method, and complementarity-determining region (CDR)-targeting quantitation.
Minimizing peptide complexity while maintaining specificity of antibody signature peptides is essential for antibody LCMS bioanalysis. To the best of our knowledge, CDR-selective preparation in antibody proteolysis has never been investigated to date. We have reported a novel method for the Fab-selective proteolysis to identify and quantify antibodies by the limiting protease access to the substrate, which we have named nano-surface and molecular-orientation limited (nSMOL) proteolysis. nSMOL enables efficient and quantitative detection of CDR peptides while decreasing the peptide numbers of the analytical target without denaturation. We have reported several papers for fully validated bioanalysis of antibody drugs. This approach will be applicable for many monoclonal antibodies and biosimilar drugs. Furthermore, the clinical PK based on LCMS may be expected to aid acceleration of the development of biopharmaceuticals.