1st Edition

Biosimilar and Interchangeable Biologics From Cell Line to Commercial Launch, Two Volume Set

    1268 Pages 40 Color & 53 B/W Illustrations
    by CRC Press

    What’s the Deal with Biosimilars?

    Biosimilars are gaining momentum as new protein therapeutic candidates that can help fill a vital need in the healthcare industry. The biological drugs are produced by recombinant DNA technology that allows for large-scale production and an overall reduction time in costs and development.

    Biosimilars and Interchangeable Biologics: From Cell Line to Commercial Launch covers the strategic and tactical elements of biosimilars in two volumes.

    The first volume, Biosimilars and Interchangeable Biologics: Strategic Elements, explores the strategic planning side of biosimilar drugs and targets issues surrounding biosimilars that are linked to legal matters. This includes principal patents and intellectual property, regulatory pathways, and concerns about affordability on a global scale. It addresses the complexity of biosimilar products, and it discusses the utilization of biosimilars and related biological drugs in expanding world markets.

    This volume also examines the science, technology, finance, legality, ethics, and politics of biosimilar drugs. It considers strategic planning elements that include an overall understanding of the history and the current status of the art and science of biosimilars, and it provides detailed descriptions of the legal, regulatory, and commercial characteristics. The book presents a global strategy on how to build, take to market, and manage the next generation of biosimilars throughout their life cycle.

    The second volume, Biosimilars and Interchangeable Biologics: Tactical Elements, explores the development and manufacturing of biosimilars and targets challenges surrounding the creation of these products. This includes manufacturing, production costs, and intellectual property barriers, particularly in regulated markets (regulatory agencies are still in the process of developing guidelines). It addresses the complexity of biological drugs, and it discusses specific structural elements vital to the functionality, immunogenicity, and safety of biosimilar products.

    This volume also provides an overall understanding of the hurdles, difficulties, and practicalities of developing a strong plan. It introduces a step-by-step approach for creating a strategy that helps develop and manufacture a biosimilar product while reducing overall production costs and meeting the requirements of biosimilarity based on analytical and functional, pharmacokinetic, pharmacodynamic (where applicable), and nonclinical toxicology or toxicokinetic similarity (where appropriate) while remaining competitive in the market.

    Thus, Biosimilars and Interchangeable Biologics: From Cell Line to Commercial Launch, Two-Volume Set supplies practitioners, researchers, and scientists in the biopharmaceutical industry with a valuable resource for practical information at all stages of the biosimilar product process.

    BIOSIMILARS AND INTERCHANGEABLE BIOLOGICS: STRATEGIC ELEMENTS

    Introduction to Biosimilar and Interchangeable Products
    Background
    Manufacturing Systems
    Characterization Systems
    European Perspective on Interchangeability
    Legality of Interchangeability
    Interchangeability Practices
    The Naming Controversy
    Label
    Regulatory Approvals
    EMA Status
    Regulatory Filing Under 505(b)(2)
    eCTD Filing Requirements
    Analytical Similarity
    FDA Views on Development of Biosimilars
    Nonclinical Testing
    Immunogenicity
    Phase III Trials
    Pharmacovigilance
    Commercial Opportunities
    Epilogue
    Bibliography

    Intellectual Property Issues for Biosimilars
    Global Patenting Perspective
    Biological Patents
    Patent Linkage
    Purple Book
    Patent Term Extension
    Patent Term Adjustment
    Determination of Target Launch Dates for Biologics
    Loss of Patent Exclusivity
    Freedom-to-Operate Opinions
    Filing the 351(k) Triggers the Patent Dance
    First Patent Dance Failed
    Notice of Commercial Marketing and Preliminary Injunction
    Sources of Uncertainty
    Interchangeability
    Bibliography

    European Regulatory Guidance
    Background
    Publication of Clinical Data
    2014 Update
    Product-Specific Guidance
    Clinical Safety
    Conclusion
    Bibliography

    EMA-Approved Biosimilars
    Background
    Somatropin (Omnitrope)
    Hyaluronidase
    Enoxaparin
    Filgrastim
    Somatropin
    Erythropoietin
    Follitropin Alfa
    Infliximab
    Conclusion
    Bibliography

    FDA Regulatory Guidance
    Background
    Historical Perspective
    Nonclinical Studies for Biologics
    Biologics License Application
    Guidance for Biosimilars
    Biosimilarity
    Clinical Pharmacology Data to Support Biosimilarity
    Purple Book
    Conclusion
    Bibliography

    ROW Regulatory Guidance
    Background
    Argentina
    Australia
    Brazil
    Canadian Guidelines on Subsequent Entry Biologics (SEBs)
    Singapore
    China
    India
    Islamic Republic of Iran (National Regulatory Authority)
    Japan
    Jordan Food and Drug Administration
    Mexico
    Russia
    South Korea
    Turkey
    United States of America
    World Health Organization (WHO)
    Bibliography

    US Commercialization
    Background
    Competition
    Evolving Pharma Market
    Industry Overview
    Commercializing a Biosimilar
    Industry Events and Forums
    Print Materials
    Advertising
    Social Media
    Website
    Bibliography

    Global Commercialization
    Background
    Product Naming Issues
    Bibliography

    Quality and Lifecycle Management
    Background
    Pharmaceutical Development
    Critical Quality Attributes
    Product Life Cycle Management and Continual Improvement
    Quality Risk Management and Product and Process Development
    Differing Approaches to Pharmaceutical Development
    CMC Considerations for the Drug Substance
    CMC Considerations for the Drug Product
    Life Cycle Management
    FDA Comparability Protocol (CP)
    CP Compilation Summary
    Applicability of a CP
    Components of a CP Submission
    Reporting of the Manufacturing Change(s) Implemented Using an Approved CP
    Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process (Q5e)
    Operational Systems
    Quality Control Systems
    Bibliography
    Appendices

    BIOSIMILARS AND INTERCHANGEABLE BIOLOGICS: TACTICAL ELEMENTS

    Structural and Functional Elements
    Basics
    Multidimensional View
    Primary Structure
    Secondary Structure
    Tertiary Structure
    Quaternary Structure
    Posttranslational Modification (PTM)
    Protein Folding
    Protein Structural Variability
    Recombinant DNA
    Bibliography

    Immunogenicity Considerations
    Introduction
    Immune System
    Antigens
    Antibody
    Protein Immunogenicity
    Biosimilar Product Immunogenicity
    Immunogenicity Testing
    Conclusion
    Bibliography

    Product Development Strategies
    Background
    Selection of Product
    Manufacturing System Selection
    Cell Line Choice
    Reference Product
    Test Method Development
    Specifications
    Reverse Engineering
    Analytical and Functional Similarity
    Nonclinical Studies
    Clinical Pharmacology Studies
    Interchangeability Protocols
    Regulatory Uncertainty
    Legal Teams in Place
    Commercialization Challenges
    Bibliography

    Stability and Formulation Considerations
    Introduction
    Formulation of Biosimilar Products
    Common Formulation Elements
    High Concentration Formulations
    Stability Testing Guidance
    Bibliography

    Biosimilarity Tetrahedron
    Tetrahedron Concept
    Similarity Concept
    Comparability versus Similarity
    Analytical and Functional Similarity
    Analytical Instrumentation
    Identity
    Purity
    Potency
    Safety
    Clinical Data
    Risk-Based Critical Quality Attributes
    Nonclinical Data
    Stages of Analytical Similarity
    Level of Similarity
    Statistical Modeling of Similarity Data
    Interchangeability
    Conclusion
    Bibliography

    Recombinant Expression Systems
    Background
    Expression System Development
    Manipulations to Improve Yield
    Mammalian Cells Expression Systems
    Mammalian Cell Expression Improvements
    Yeast Expression Systems
    Insect Cells
    Transgenic Animals
    Cell Banks
    Bibliography

    Upstream Systems Optimization
    Background
    Bacterial Manufacturing Systems
    Mammalian Manufacturing Systems
    Yeast Cell Manufacturing Systems
    Transgenic Animal Systems
    Cell Lines and Characterization
    Future Prospects
    Bibliography

    Downstream Systems Optimization
    Introduction
    Bacterial Downstream Processing
    Mammalian Downstream
    Yeast Downstream Processing
    Insect Cell Processing
    Transgenic Animals Processing
    Bibliography

    Single-Use Manufacturing Systems (SUMS)
    Background
    Safety of Single-Use Systems
    Polymers and Additives
    Regulatory Requirements
    Risk Assessment
    Single-Use Containers
    Summary
    Single-Use Mixing Systems
    Connectors and Transfers
    Filtration
    Controls
    Filling and Finishing Systems
    Environmental Concerns
    Bibliography

    Commercial Manufacturing Overview
    Introduction
    Media
    Culture Growth
    Process Overview
    Process Maturity
    Validation
    Scale-Up
    Specific Scale-Up Issues
    Specific Economy Issues
    Process Materials
    Environment Control
    Biosafety Levels
    Good Manufacturing Controls of Active Pharmaceutical Ingredients
    Cleaning Procedures
    Processing and Filling
    Laboratory Testing
    Laboratory Controls
    Documentation
    Bibliography

    Outsourcing Considerations
    Background
    Value of Outsourcing
    Factors to Consider in Outsourcing
    Key Requirements
    What to Outsource?
    Cell Line Suppliers
    CMOs
    Biopharmaceutical Support Services
    Analytical Support Providers
    Contract Research Organizations
    Product Development Services
    Fill and Finish Providers
    Legal Matters
    Managing Outsourcing
    Outlook

    Biography

    Sarfaraz K. Niazi, PhD, is the founding executive chairman of Therapeutic Proteins International LLC, a world-class pure-play developer and manufacturer of biosimilar and interchangeable recombinant biologics, headquartered in Chicago. Dr. Niazi began his career teaching pharmacy at the University of Illinois (1972–1988), where he became a tenured professor. He then entered the pharmaceutical industry at Abbott International, becoming a Volwiler Fellow. He left Abbott in 1995 with a passion for making high-cost biological drugs affordable. Dr. Niazi set up several ex-U.S. biosimilar companies and, in 2003, established Therapeutic Proteins International, the only U.S. integrated company of its kind to date.