Table of Contents

5 EXECUTIVE SUMMARY
5 Regulatory pathway
5 Legal considerations
6 Pricing, reimbursement, and access
7 Education needs
8 THE NEED FOR BIOSIMILARS
8 What are biosimilars?
8 The US has lagged behind the EU in developing a regulatory process for biosimilars
9 Biosimilars are expected to deliver considerable cost savings for the US healthcare system
10 There are several questions around biosimilars that need to be addressed
11 Bibliography
13 REGULATORY PATHWAY
14 Omnitrope was a “copy” biologic that was approved prior to 2010 via the 505(b)(2) process
15 The BPCI Act established a dedicated biosimilar approval pathway in the US
16 FDA released guidance on biosimilar approval requirements
20 There are still several uncertainties around the regulatory pathway in the US
22 Indication extrapolation poses the greatest regulatory uncertainty for manufacturers
29 There are several key differences in US and EU approval processes
32 Zarxio was the first biosimilar to be approved through the BPCI Act pathway
33 Bibliography
38 SUBSTITUTION AND NAMING POLICY
38 Biosimilars naming is a contentious issue yet to be resolved
39 Biosimilar labeling is also a key issue
39 Substitution policies are likely to vary across states
45 Bibliography
47 LEGAL ISSUES
47 The innovative industry lobby secured a long period of exclusivity for biologics
48 Biologics currently have four years of data exclusivity followed by eight years of market
exclusivity
50 Patent litigation is being pursued by many originator companies
59 Bibliography
62 PRICING, REIMBURSEMENT, AND ACCESS
62 Different tools are used to control spending on biologics
63 Biosimilars are expected to offer at least 20% discounts relative to the brand
68 Biosimilar use will be driven by a number of measures
80 Payers’ drive to promote biosimilar use depends on the indication
82 Payers will treat biosimilars as brands
83 Accountable care organizations and group purchasing organizations will have an interest in
using biosimilars
84 Bibliography
87 EDUCATION AND COMMUNICATION NEEDS
87 There are still residual uncertainties regarding biosimilars in the eyes of many stakeholders
87 A large proportion of physicians have concerns about biosimilars
90 Patients likely to accept biosimilars
92 Education around biosimilars is critical for access and uptake in the US
95 Concerted education efforts are required in order to boost biosimilar acceptance and use
97 Bibliography

LIST OF FIGURES

8 Figure 1: Definitions of various types of biologics and copy products
9 Figure 2: Key events in the evolution of regulatory environments for biosimilars
14 Figure 3: Approval pathways available for biologics in the US
51 Figure 4: Information exchange steps between biosimilar manufacturers and reference product
patent holders
76 Figure 5: Biosimilars reimbursement under Medicare Part B
92 Figure 6: US healthcare professionals’ understanding of biosimilars
95 Figure 7: Key organizations involved in stakeholder education about biosimilars

LIST OF TABLES

13 Table 1: Key US biosimilar regulatory events
15 Table 2: Committees created to support biosimilar approval
16 Table 3: FDA guidance on biosimilars published to date
19 Table 4: Key scientific principles used for biosimilar application review
23 Table 5: Regulatory considerations for indication extrapolation for biosimilars
28 Table 6: Factors influencing physician acceptability and likelihood of indication extrapolation
29 Table 7: Differences in US and EU biosimilar definitions, regulatory guidance, and other key
regulatory factors influencing biosimilar approval and use
40 Table 8: Biosimilar substitution: state laws and legislation
47 Table 9: Key features of the BPCI Act
49 Table 10: Data, market exclusivity, and patent expiry dates in the US for selected biologics
54 Table 11: Summary of ongoing legal challenges
62 Table 12: Utilization tools for the management of biologics spending
68 Table 13: Utilization tools applied to biosimilars
80 Table 14: Payer strategies aimed at increasing biosimilar uptake will vary by indication and
product characteristics