Day 1 :
Keynote Forum
Peter Bernhardt
Momenta Pharmaceuticals, USA
Keynote: Fingerprint-like similarity: Making the connection between product characteristics and clinical outcomes
Time : 09:50-10:40
Biography:
Peter Bernhard is a Biotechnology professional with significant technical leadership experience and a proven track record in Analytical and CMC Development. He quickly and fearlessly gets to the heart of situations, identify areas for improvement, and then seek to implement creative and efficient solutions that generate value. His continuous improvement mindset and drive towards future possibilities, combined with his action-oriented nature and ability to navigate around obstacles, allowed him to excel at initiating and executing new projects or developing and refining business processes. He is a quick thinker and learner who can assimilate information from multiple sources and then communicate this information effectively and clearly to the target audience.
Abstract:
Analytical similarity assessments typically focus on comparing the physical, chemical and functional properties of a biosimilars product to the reference product, to understand where the two products are similar and where they are not similar. An attempt is then made to justify why observed differences will or will not impact the clinical outcomes (e.g. safety, including immunogenicity, efficacy, PD or PK). The justification typically requires making a bridge between an observed difference and a clinical outcome via some type of a functional assay. This type of assessment is only as good as the assays being used (e.g. what level of difference would have to be present in order to observe a difference in the functional response). When differences are observed, new or more sensitive assays may be developed, independent of a relationship between the observed
difference and a clinical outcome. We argue that if one starts from a detail understanding of the product, clinical indications,
and safety profile of the reference product and other similar products, then one can a priori determine which physical, chemical
and functional attributes are either known to impact or likely to impact the clinical outcomes. Using this knowledge, attributes
can be identified that may require a detailed understanding of the relationship and interrelationship(s) between the attribute
and the clinical outcomes as well as between attributes and the clinical outcomes (e.g. is there a relationship between high
mannose and sialic acid levels on PK?). With this knowledge first, methods are developed, along with the appropriate controls,
that have the sensitivity required to detect meaningful differences. The assessment of fingerprint like similarity can then be
based on (1) both the full physical and chemical comparison of the product to the RPP and (2) the detailed analysis of the key
properties, with sensitive assays, that allow linkage between key product attributes and clinical outcomes. We will provide an
overview of our view on fingerprint-like similarity and how it can be applied to biosimilars development.
Keynote Forum
Laszlo Endrenyi
University of Toronto, Canada
Keynote: Interchangeability, switch ability and substitution of biosimilars drug products
Time : 11:10-12:00
Biography:
Laszlo Endrenyi is a 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 served as 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. He has published
books on Kinetic Data Analysis and Biosimilar Drug Product Development, and over 200 research papers. He has advised and widely consulted with industry and
regulatory agencies.
Abstract:
The assessment of and 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 bio similarity 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.
- Globalization of Biosimilars | Clinical Development Of Biosimilars | Regulatory Approach for Biosimilars
Location: Sierra
Chair
Laszlo Endrenyi
University of Toronto, Canada
Session Introduction
Deven V Parmar
Cadila Healthcare Limited, India
Title: Evaluation of biosimilar Bevacizumab in the treatment of Indian patients with nonsmall- cell lung cancer
Time : 12:00-12:30
Biography:
Deven V Parmar is Head and Vice President, Clinical R&D, Cadila Healthcare Limited, has his expertise in clinical drug development and biosimilar development. He is a Clinical Pharmacologist by training, with 25 years of clinical research experience work across various geographies
Abstract:
Statement of the Problem: The role of bevacizumab in combination with carboplatin/paclitaxel chemotherapy has been established in patients with non-small-cell lung cancer (NSCLC). This trial was designed to evaluate the effect of Zydus biosimilar bevacizumab compared to innovator’s bevacizumab in Indian patients with NSCLC.
Methodology: A multicentre, prospective, randomized, open-label, active controlled study was carried out on 248 patients with
advanced, unresectable, recurrent or metastatic NSCLC at 28 sites across India. Patients were randomized in 2:1 (169:79) ratio to
receive intravenous infusion of 15 mg/kg of test bevacizumab or reference bevacizumab, plus paclitaxel 175 mg/m2 and carboplatin
(AUC 5 mg/mL×min) every three weeks for six cycles. Overall response rate (ORR) after treatment of 6 cycles was assessed by
using response evaluation criteria in solid tumors (RECIST 1.1). Pharmacokinetics (Cmax and AUC0-t), safety and tolerability, and
immunogenicity were also assessed.
Findings: All patients were of Asian origin and males comprised >70% of the population in both the groups. The mean age was 57±9.71
years in test bevacizumab and 58±11.35 years in reference bevacizumab. Baseline characteristics were balanced and no statistically
significant difference was observed between both the groups. The ORR was 60.82% (59 out of 97 subjects) in Bevacizumab (Zydus)
group and 58.82% (30 out of 51 subjects) responders in the reference Bevacizumab and 90% confidence interval for the difference of
overall response rate fell within the ±20% equivalence margin (-11.96, 15.97). The pharmacokinetic assessment of the In-transformed
bevacizumab after Cycle-1 data showed the 90% confidence intervals for the ratio of the Test geometric least square mean to reference
geometric least square mean within the 80.00% to 125.00% limits for Cmax (87.99%;120.41%) and AUC0-t (90.70%;122.03%). The
incidence of immunogenicity in the test product treated group was marginally lower compared to the reference drug product treated
subjects (72.16% vs. 76.47%).
Conclusion: The results demonstrated biosimilarity between Zydus bevacizumab and innovator’s bevacizumab with respect to
efficacy, tolerability and safety in Indian patients with NSCLC.
Arthur G Cook
ZS Associates, USA
Title: The commercial landscape for biosimilars: Planning in an uncertain environment
Biography:
Arthur G Cook is a Principal with ZS Associates in San Francisco, CA. His experience is in strategic planning, forecasting, market research, pricing, and decision analysis.
He has worked with pharmaceutical companies across 25 countries in North America, Latin America, Asia, Europe, and Australia and has developed forecasts for products
in over 150 different therapeutic areas. His experience prior to joining ZS Associates includes positions at two major pharmaceutical companies. He also has been a featured
speaker at numerous pharmaceutical and health care industry conferences and is the author of the 2015 second edition book entitled Forecasting for the Pharmaceutical
Industry. Currently, he heads the Biosimilars Center of Excellence at ZS Associates. He holds an MBA from the University of California at Berkeley, a PhD in Chemistry from
Harvard University, and a BS in Chemistry from Stanford University
Abstract:
Over the next 10 years $71 billion in worldwide biopharmaceutical revenue may be affected by the launch of biosimilars products.Several biosimilars launches already have taken place in multiple European countries, and observations from uptake in these markets hold insight for strategic planners, both in Europe and other geographies. In countries such as the US the commercial landscape is complicated by additional uncertainties in regulatory and legal policy. In this talk we will examine the learning from prior launches and apply these insights in a decision analysis framework to aid in planning for future biosimilars introductions. In particular we will address the challenges of forecasting biosimilars uptake and innovator erosion.
Ravindra Patel
OmniBRx Biotechnologies, India
Title: An overexploitation approach for cell culture based modular bioprocessing
Biography:
Ravindra Patel is an Inventor, Founder and CEO of OmniBRx Biotechnologies Pvt. Ltd. He has invented the DBR technology (Patent Pending) for ADC range of single-use bioreactors, the first in-class SUB’s offering very efficient high density cell culture in small culture volume. He holds 10 years of enriched experience in the field of Bioprocessing and Biotechnology research. He is pursuing his PhD in Biotechnology from DYPU, Mumbai. He did his Master’s in Biotechnology from Sardar Patel University, Gujarat.
Abstract:
In the battle of controlling healthcare costs, the high cost pharmaceuticals, especially biologics has become an important issue.
Successful production planning requires consideration of cost factors such as manufacturing cost, capital investment to build
new facilities or to retrofit existing ones, as well as the inventory costs. The cost attributed to the opportunity lost in selling the
product or failure to meet market demand is also considered as the inventory cost. Any unplanned downtime could severely affect the
customer service level, if facility utilization is too high. Underutilization of manufacturing facilities conversely suggests a misplaced
investment in capacity. The overexploitation approach was designed to mitigate the above described facility constrains due to its
power of combining the benefits of perfusion and fed batch processing mode with adequate elimination of facility constrains of fedbatch
bioprocessing was done. The key factors considered are: adapting to modular single use technologies for facility design; smallest
mall footprint for upstream processing saves initial investment, significantly; multiproduct facilities to be designed capable of offering
production output in kilograms per month; completely avoiding the use of conventional stainless steel bioreactors and culture revived
from single low-passage cell bank can be expanded for several months without compromising the product quality. With continuous
processing advantage while adapting an overexploitation approach, the cultured cells can be processed up to 60 passages, typically.
Md Abu Zafor Sadek
University of Dhaka, Bangladesh
Title: Global Status of Biosimilars & Prospects in Asia
Biography:
Md. Abu Zafor Sadek has been serving as a Senior Additional Manager at Renata Limited, one of the top tier pharmaceutical companies of Bangladesh. Being graduated in Pharmacy from Khulna University, he started his career at Orion Pharmaceuticals Limited as Product Executive. Thereafter, he completed his MBA in International Business from Dhaka University. He has more than 10 years career in pharmaceutical management with excellent track record. His area of interests includes launching time demanded new products, brand management, strategy formulation, business opportunity identification, international business, training, presentation skills etc. In addition to his regular job, he is perusing for Doctor of Business Administration (DBA) Degree on growth potential of biosimilars products in Bangladesh from Institute of Business Administration (IBA), Dhaka University, and the leading business school of the country. He has four publications in different local and international journals. He has presented biosimilars and other topics at different conferences around the world including 5th European Biosimilars Congress, Valencia, Spain and 2nd Biosimilars Asia-Pacific Summit, Singapore. He is also involved in writing health column for the leading Bangladeshi newspapers
Abstract:
Almost one decade back the first biosimilars was launched in Europe. Now they have 15 biosimilars and all are well accepted since
high price branded biologics were tough to reach by many patients. Recently biosimilars has been endorsed everywhere in the
world starting from developing to developed countries. United States Food and Drug Administration (USFDA) approved the first
biosimilars in 2015 and currently they have 03 biosimilars which are playing pivotal role in price cutting of branded biologics. They
also have many biosimilars to be launched shortly. Australia, Canada, Africa and Asia are also aggressive with biosimilars specially
India, Korea, China made remarkable effort in biosimilars. However, considering the changes in disease pattern, increasing use of
biological drugs, huge number of population, rising health awareness, recent economic growth, success history of some biologic
companies, dependence on generic items, price sensitivity, relax regulation, growing health budget, very low production cost and
other relevant factors, Asia is an important hub for biosimilars. Therefore, this study found out the prospects of biosimilars in Asia.
Anka G Ehrhardt
Bristol-Myers Squibb Co., USA
Title: Receptor occupancy in flow cytometry: A key PK/PD option in biologics clinical studies
Biography:
Anka G Ehrhardt is a Biophysicist with a Doctorate degree in Human Physiology. She is currently working in the United States Building and directing a team applying the latest technologies in support of the development of new live saving drugs
Abstract:
Receptor occupancy assays are a key method in dose escalation studies to understand the amount of drug required to cover the available receptors during patient dosing, as well as to deliver PK data for PK/PD work. For many biologics, flow cytometry assays utilizing peripheral blood are well suited for receptor occupancy studies, and are used often in the clinic. This presentation will summarize some of the common considerations and different versions of RO assays in the context of clinical studies.
- Emerging Biosimilars in Therapeutics | Biosimilars Analytical Strategies | Regulatory Approach for Biosimilars
Location: Sierra
Chair
Mayra Liz Guzman-Kaslow
GK Regulatory Compliance & Engineering Consulting Corporation
Session Introduction
Asif Mahmood
Pfizer, USA
Title: Biosimilars: Challenges in safety and risk management
Time : 11:50-12:20
Biography:
Asif Mahmood has diverse leadership experience as a health services professional with significant accomplishments in all aspects of pharmacovigilance, clinical development, medical affairs, regulatory affairs, primary health care, project management & international health programs. He is currently working as Disease Area Cluster Lead for Biosimilars & Drug Delivery Devices at Pfizer. His past experience includes working as Associate Vice President PV and Therapeutic Area Head (Rare Diseases) for Sanofi
Genzyme, working as Senior Director & Director for vaccines PV at Sanofi Pasteur and working as Medical Consultant for Apotex Inc., Canada. Prior to joining industry, he has worked as Joint Executive Director for Pakistan Institute of Medical Sciences, Registrar of the Post-graduate Medical Institute PIMS and as Deputy Director General of Ministry of Health, Pakistan. He has also worked on various primary healthcare, public health, and health planning & development programs as well as on World Food, UNICEF; WHO & JICA assisted programs on drug safety, emergency preparedness and primary healthcare.
Abstract:
Advances in biotechnology have ensured a world of opportunities for biosimilars to enter the market and serve the needs of patients in a cost-effective manner. However, pharmacovigilance and risk management for biosimilars present a significant challenge that arise from their unique characteristics as biologics as well as from their differences with the reference innovator products. Traditional PV processes may not incorporate sufficient provisions to meet the particular requirements for biosimilars. While a biosimilar and its reference drug can show similar efficacy, it can exhibit a different safety profile with respect to the nature, seriousness or incidence of reported adverse events (AEs). Therefore, there is a need to clearly identify the specific product associated with the AE. Hence, product naming is an important consideration for biosimilars traceability. The potential for immunogenicity represents an important safety concern with all biologics, including biosimilars. The nature and severity of immunogenic reactions
may differ from those observed for the reference innovator and immunogenicity data from the reference product may not be directly
extrapolated to the biosimilar. Given the relatively small number/size of clinical trials required for regulatory approval of biosimilars,
full characterization of the immunogenicity profile of a biosimilar may not be established at the time of regulatory approval. Continued post-marketing surveillance of biosimilars is critical for effective risk management. Also, the unique nature of biosimilars requires a labeling approach that combines data on the reference product with data specific to the biosimilar due to differences in their source materials, manufacturing processes and impurities. Finally, the safety specifications in the RMP of a biosimilar should include the identified and potential risks of the reference innovator product as well as risks identified from studies on the specific biosimilar product.
Biography:
Dr. Sunit was trained as Developmental/Cardiovascular Biologists in Leuven, Belgium where he received his PhD. He worked in industry (Mermaid Pharmaceuticals, Hamburg Germany) for several years where he was involved in target identification using model system. He has spent time at Max Planck Institute where he was involved in the CNS development related project. After coming back to India in 2007, he joined Avesthagen where he headed the biosimilar group. He was responsible for development of biologics including recombinant protein and monoclonal antibodies using mammalian expression system. He is associated with Zumutor Biologics since its inception and
currently heads the Product Development team.
Abstract:
Monoclonal antibodies are high molecular weight proteins (~150 kDa). As is common for biotech-derived molecules of this size, they have highly complex secondary and tertiary structures, subject to post-translational modifications. Heterogeneity of monoclonal antibodies due to the vast number of modifications presents great challenge to the thorough characterization of the molecules. Different orthogonal techniques are required to understand the structure and stability of the molecules thoroughly. The major challenge in developing biosimilar monoclonal antibody is to evaluate what impact certain quality attributes do have on clinical efficacy and safety, and what level of difference is acceptable from a biosimilarity perspective. Different modifications and challenges in developing biosimilar monoclonal antibody will be discussed.
K Aftab
Isra University Karachi, Pakistan
Title: Biosimilars: Challenges in safety and risk management
Biography:
K Aftab, PhD, Pharmacologist, graduated from Department of Pharmacology, Faculty of Pharmacy, University of Karachi, Pakistan in 1995. He worked for pharmaceuticals industry as Quality Control & Quality Assurance Professional and was actively involved in research & development of pharmaceutical preparations. He has worked in few medical & dental colleges & universities as Assistant, Associate and became Full Professor of Pharmacology in 2005 and also worked as Visiting Professor in different universities & research institutions. From 2009-2011, he worked in KSA as a Full Professor of Pharmacology. Now, he has published more than 35 papers in scientific journals of international repute and presented many lectures & poster presentations throughout the world; most awards to him were for the science and technology success. He was involved in drug discovery and the scientific evaluation of traditional remedies used in different disorders. His group has developed expertise in a wide range of activities and made valuable contributions on medicinal value of plants by providing pharmacological basis for their usefulness as antihypertensive, cardio-tonic, laxative, antispasmodic
and anti-diarrheal. In recent years, he focused on the biodiversity & pharmacological activities of marine organisms.
Abstract:
Holarrhena pubescens belongs to the family Apocynacea, commonly known as “Kurchi” is highly reputed in traditional medicine as a remedy for amoebic dysentery and other intestinal ailment. Bioassay-directed fractionation of the ethanolic extract of Holarrhena pubescens resulted in the isolation of steroidal alkaloids i.e. holamide and pubscinine. Holamide showed a three proton
doublet at 1.45 (J=6.56 Hz) and two AB doubles at 3.17 and 3.00 each for on proton (J=12.06 Hz) in the 1H NMR spectrum suggested that it belongs to conanine series of alkaloid (A class of compound with the steroid nucleus and a five members heterocyclic ring with nitrogen). In contrast, pubscinine showed one methyl at 1.28 while the doublet is missing a three proton singlet was observed at 2.28 due to a vinylic methyl indicated a double bond in the 18,20–epimino ring of the conanine series of alkaloids. In anaesthetized rats,
the holamide and pubscinine caused a fall in blood pressure in a dose-dependent manner. Pretreatment of animals with atropine completely abolished the hypotensive response of acetylcholine; whereas hypotensive effect of holamide and pubscinine were not modified by atropine. Similarly, acetylcholine produced contractile effect in guinea-pig ileum, which was antagonized by atropine, however both (holamide and pubscinine) failed to produce any stimulant response on guinea-pig ileum. These data indicate that the steroidal alkaloids i.e. holamide and pubscinine from Holarrhena pubescens mediated hypotensive response through a mechanism different to that of acetylcholine.