Biosimilars Series: Regulatory and development issues hurdles exist but are surmountable : Market Research Report

Biosimilars Series: Regulatory and development issues hurdles exist but are surmountable

Published by: Datamonitor

Published: Sep. 13, 2007 - 135 Pages

CHAPTER 1 EXECUTIVE SUMMARY: Scope of the report; Key findings; Key definitions
CHAPTER 2 INTRODUCTION TO THE BIOSIMILARS MARKET: Drivers and resistors of the biosimilars market growth; Drivers of growth in the biosimilars market; Biologics are the fastest growing segment of the pharmaceuticals market; Patent expiry on first-generation biologics; Increasing pressures of cost-containment; Advances in analytical techniques; Resistors of growth in the biosimilars market; Opposition from the innovator companies; Lack of biosimilars regulatory approval pathway in the US is stalling the entry of biosimilars into the US market; Cost and complexity of development; Lack of time on market hinders physician uptake
CHAPTER 3 BIOSIMILARS REGULATORY ISSUES: Europe is leading the way in biosimilars legislation and approval; Guideline on quality issues for biosimilars is based on analysis of comparability after process change; Guidelines on pre-clinical and clinical issues are vague; Results of clinical trials could be extrapolated to other indications in some cases; Product-class specific annexes provide more details; Route of administration used in clinical trials is critical; Five biosimilars have been approved in the EU; Omnitrope's approval forced a change of law to allow approval of biosimilars; BioPartners's Valtropin received approval but Alpheon failed on quality issues; Three biosimilar Epoetins have been approved in Europe; Further guidance is expected; Other regulatory issues in Europe remain; The Bolar provision - a safe harbor for development of biosimilars; Use of trade secret data; Innovators insist that biosimilars should have unique INNs; Others will follow where EU leads; Opposing interests hinder progress in the US; The FDA has delayed issuing guidance for approval of biosimilars; The FDA has already approved follow-on protein products; Avonex marks approval of a first biosimilar; Follow-on hyaluronidase approval; Glucagon and Fortical (salmon calcitonin nasal spray) follow-on protein products; Sandoz's Omnitrope; The FDA's decision to use the abbreviated approval pathway for Omnitrope was met with criticism; Recent activity in the US Senate and Congress suggests legislation on biosimilars approval might be issued in the near future; The Access to Life-Saving Medicine Act is pro-biosimilar and was not accepted by the pro-innovator faction; The Patent Protection and Innovative Biologic Medicines Act of 2007 is pro-innovator; The Biologics Price Competition and Innovation Act of 2007 proposes a middle-of-the road solution; Impact of future legislation on the FDA's biosimilars approval pathway; What happens before legislation is passed?; Abbreviated or full submission routes?; Strategies for innovators to minimize the effect of biosimilar competition; Naming of biosimilars remains an issue in the US; Automatic substitution with biosimilars or not - an unresolved issue; Automatic substitution in the US is unlikely; Substitution policies are defined by individual member states in the EU; Will reimbursement incentives drive biosimilar substitution?
CHAPTER 4 BIOSIMILARS DEVELOPMENT ISSUES: Biosimilars producers have to develop their own manufacturing process; Development of a manufacturing process for biosimilars involves many steps; Process knowledge is key; Choice of cell line is important; Patent protection of biologics is complex; Demonstration of comparability and similarity employs the same techniques; Product knowledge is critical for designing analytical testing strategy; Advice from regulators is invaluable; Lack of experience and data makes defining acceptance margins difficult; Analytical testing of biosimilars; Limitations of analytical testing; Primary sequence analysis; Misfolding can have a serious impact on clinical performance; Different processes result in different heterogeneity profiles - critical factor to explore; Post-translational modifications are a major cause of heterogeneity; Differences in glycosylation patterns need to be investigated; Presence of aggregates can have negative effects on a protein's clinical profile; Differences in hydrophobicity and charge need to be investigated; Stability testing of biosimilars; Comparability after process change; Choice of reference product is important; Some originator products exhibit great inter-batch variability; Pre-clinical testing of biosimilars; Biological activity assays are used in pre-clinical testing of biosimilars; Animal studies have limited value; Pre-clinical safety studies; Immunogenicity testing is critical for approval; Factors influencing the potential of a protein product to elicit an immune response; Immunogenicity considerations are especially important for therapeutic antibodies.; Pre-clinical immunogenicity testing; In vitro methods used in clinical immunogenicity testing; Aggregates have the capacity to trigger immune response; Differences in glycosylation can lead to enhanced immunogenicity; PRCA associated with Eprex led to increased focus on immunogenicity; Final formulation and packaging; Formulation can impact the clinical profile; Differences in packaging can have an effect on safety; Second-generation biosimilars have different formulation and packaging; Clinical trials are necessary for approval of biosimilars; Clinical trials are the longest and most expensive part of the comparability demonstration; Comparative PK studies of biosimilars; Comparative PD studies of biosimilars; Comparative efficacy studies of biosimilars; Clinical safety studies of biosimilars; Clinical immunogenicity testing of biosimilars; Risk management plans are important; Pharmacovigilance plans are necessary for approval of biosimilars; Scientific advice from regulatory bodies; Comparable or interchangeable?; Can a biosimilar be better than the originator's product?; The EMEA has been flexible in its approval of biosimilars to date; Omnitrope was approved by the EMEA despite changes in the purification procedure of the final product; Approval of Valtropin demonstrates the importance of using the correct reference product; BioPartners's Alpheon was rejected on grounds of quality issues; Three biosimilars of Eprex were approved by the EMEA; Finding information about previous approvals is not straightforward; Development strategies for biosimilar manufacturers; A detailed development plan can help avoid pitfalls; Third party advice; Strategic collaborations are used to gain access to complementary competencies; Acquisitions are used to acquire biosimilar pipelines or production facilities
CHAPTER 5 FUTURE DEVELOPMENTS: The EMEA will issue further guidelines; Which biosimilars will be approved next?; The future of biosimilars in the US depends on whether a consensus can be reached in Congress; If the Senate bill is accepted the US will be a more lucrative market; What about other markets?; Biosimilars of monoclonal antibodies; Monoclonal antibodies will not be open to biosimilar competition for several years; Manufacturing and comparability of biosimilar mAbs; New technologies allowing controlled glycosylation are emerging; Regulatory approval of mAbs; The big players are most likely to enter this market
BIBLIOGRAPHY: Publications and online articles; Websites; Conference literature; Datamonitor resources; Suggested reading
GLOSSARY
List of Tables: Table 1: Patent expiries of selected key biologics; Table 2: Safety and efficacy study duration and extrapolation to other indications for different classes of biosimilars; Table 3: Statutory pathways for the approval of small molecule drug generics in the US; Table 4: Three bills regarding biosimilars were introduced in 2007
List of Figures: Figure 1: Drivers and resistors of the biosimilars market growth; Figure 2: The EMEA has published several guideline documents on biosimilars; Figure 3: The Access to Life-Saving Medicines Act is pro-biosimilar; Figure 4: The Patent Protection and Innovative Biologic Medicines Act is pro-innovator; Figure 5: The Biologic Price Competition and Innovation Act balances the interests of the public, biosimilar manufacturers and innovators; Figure 6: Manufacturing of biosimilars involves many steps; Figure 7: Relevance of different tests and studies used to characterize biosimilar products; Figure 8: EMEA's recommendations for the detection and characterization of antibodies in patients' sera

Abstract

Introduction

Europe serves as a model for other countries looking to define their own regulatory approval criteria. The US is on the brink of passing legislation to establish a statutory pathway for biosimilars approval but the opposing interests of biosimilar and innovative companies may result in further delays. Development of biosimilars presents many challenges and potential pitfalls.

Scope

Overview of the key drivers and resistors of the biosimilars market growth Analysis of the regulatory requirements for approval of biosimilars in Europe Overview of the progress the US has made in establishing its approval pathway In-depth analysis of the challenges of biosimilars development, including potential technical pitfalls and considerations

Highlights

Europe has shown a degree of flexibility in its approval of 5 biosimilars to date. Although guidance has been issued biosimilar developers are urged to communicate with the EMEA as approval remains on a case-by case basis. Naming of biosimilars remains a contentious and unresolved issue as it carries implications for substitution with biosimilars. The increasing expenditure on biologics is pressuring US lawmakers to formulate a statutory pathway for approval of biosimilars. The Biologics Price Competition and Innovation bill proposes a compromise attempting to satisfy both innovative and biosimilar companies. However its future is uncertain as it faces a slow progress in Congress. Design of the biosimilar manufacturing process is key process knowledge and understanding of potential risks and pitfalls are necessary to minimize the time and cost of development. Selection of analytical methods for assessing biosimilars quality is critical as each method answers a different question about the product.

Reasons to Purchase

Identify the key trends that are driving and resisting the growth of the biosimilars market Understand the regulatory requirements in Europe and how recent attempts to establish a regulatory pathway in the US might affect that market Gain insight into challenges and potential pitfalls in the development of biosimilars including biosimilars of monoclonal antibodies.

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Biosimilars Series: Regulatory and development issues hurdles exist but are surmountable

Table of Contents

Abstract