1st Edition

Biosimilars and Interchangeable Biologics
Tactical Elements




ISBN 9781498743495
Published December 23, 2015 by CRC Press
575 Pages 23 Color & 41 B/W Illustrations

USD $220.00

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Book Description

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.

Part of a two-volume set that covers varying aspects of biosimilars, 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.

Of specific interest to practitioners, researchers, and scientists in the biopharmaceutical industry, this volume 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.

 

 

Table of Contents

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

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Author(s)

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.