Biosimilar and Interchangeable Biologics: From Cell Line to Commercial Launch, Two Volume Set, 1st Edition (Hardback) book cover

Biosimilar and Interchangeable Biologics

From Cell Line to Commercial Launch, Two Volume Set, 1st Edition

By Sarfaraz K. Niazi

CRC Press

1,174 pages | 40 Color Illus. | 53 B/W Illus.

Purchasing Options:$ = USD
Hardback: 9781482298918
pub: 2015-12-23
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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.

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.

Table of Contents

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

About the Author

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.

Subject Categories

BISAC Subject Codes/Headings:
MED009000
MEDICAL / Biotechnology
MED071000
MEDICAL / Pharmacology
SCI010000
SCIENCE / Biotechnology
TEC059000
TECHNOLOGY & ENGINEERING / Biomedical