1. UNITED SPINAL ASSOCIATION AUGUST, 2014 Biologics & Biosimilars: An Overview 1

2. What is a biologic? 2

3. Biologics Are Complex Biologics are innovative medications that aren’t made, they are grown in living cells. Biologics are complex molecules– up to 1,000 times larger than conventional medicines. Manufacturing a biologic is a complex process that takes several months from start to finish. It’s important to remember that biologic medicines can never be exactly duplicated by two different manufacturers in the way that simpler medications can. Sources: EuropaBio, NDT Plus, Biosimilars, Nat. Biotechnol, Biopharm Int. 3

4. Biologics Have Revolutionized Healthcare Although relatively new, biologics are already used by more than 350 million patients worldwide. Biologic medicines revolutionized how diseases and conditions such as rheumatoid arthritis, Crohn’s disease, hemophilia, multiple sclerosis, and many other disorders are treated. Patterned after proteins the body itself produces, biologics can treat many serious diseases in ways conventional medicines cannot. Source: PhRMA 4

5. What is a biosimilar? 5

6. Biosimilars Biosimilars are products that are “highly similar” to (but not exact copies of) the reference biologic product. As a part of the Affordable Care Act (ACA), Congress provided the Food & Drug Administration (FDA) authority to review and approve biosimilar versions of FDA approved biologic medicines. The FDA is in the process of developing guidelines to approve biosimilars. While there are a small number of biosimilars approved in several other countries, there are currently none approved for use in the United States. The FDA received its first application for approval of a biosimilar in July 2014. 6

7. What Biosimilars Are…And Are Not As the name suggests, biosimilars are similar to a particular biologic, they are not the same. All biosimilars differ from the innovative product and from each other. They are not generic biologics. Source: Annals of Oncology 7

8. Why There Can Be No “Generic Biologics” The active ingredient of a biosimilar can, at best, only resemble that of the original biologic. How an innovator company makes its biologic can never be duplicated down to the last detail; a biosimilar is made using different cells and different processes. Source: Letter from FDA to Congress 8

9. Ensuring Safety And Effectiveness The variations between an innovator biologic and a biosimilar could potentially trigger an attack against a biosimilar by the body’s defenses.  This could cause unwanted and/or unsafe symptoms or render the biosimilar, and possibly the original biologic, less effective. To ensure comparable safety and effectiveness, biosimilars require more thorough testing than generic medicines. Source: EMA, Pharmaceutical Sciences, CDER, Biosimilar News 9

10. Issues for Patients to Consider 10

11. Access to Biologics and Patient Welfare It is important to provide access to biologic treatments for patients who need them, and biosimilars play a part in meeting this goal. An equally and perhaps more important consideration is to ensure patient safety and welfare in all stages of development, approval, and monitoring of biologics, including biosimilars. 11

12. Important Issues for Patients As federal agencies and the states implement the new biosimilars law, they are making important decisions about the regulation of biosimilars that are crucial to assuring patient safety. Interchangeability: This year, the FDA will be decide what standards must be met for a biosimilar medicine to be judged “interchangeable” with the original biologic medicine. Strict standards are needed to ensure patient safety. Rigorous Testing For Each Condition: The FDA will be determining whether drug companies must conduct rigorous clinical testing to prove that a biosimilar works safely in each distinct group of patients with that disease. Failure to perform adequate testing in each group of patients and disease type may put patients at risk. Naming: Using a distinguishable but related non-proprietary name for biosimilar medications (i.e., distinguishable from the original biologic) would enable medical professionals and the FDA to better track these products and more easily access any adverse reactions that may occur in patients who use biologics, including biosimilars. 12

13. Important Issues for Patients, (Continued) As federal agencies and the states implement the new biosimilars law, they are making important decisions about the regulation of biosimilars that are crucial to assuring patient safety. FDA Transparency: Improved transparency throughout the application and approval process of biosimilars is important to assure appropriate oversight and to ensure that all voices, particularly those of patients, are heard. Substitution/Notification: Because even an interchangeable biosimilar will not be identical to the original biologic medicine, most doctor and patient groups feel it is important for a prescribing doctor to be notified after a pharmacist substitutes a biosimilar for a prescribed biologic medicine. A biosimilar that is not interchangeable should only be used if prescribed by an appropriate health professional. Recordkeeping: Ensuring pharmacists maintain records of substitutions for significant periods of time would allow the medical community to track long-term treatment outcomes of biosimilars. 13

14. What United Spinal Association Has Said About Biosimilars “The FDA is expected to publish proposed guidance for public comment this year related to key aspects of implementation of the biosimilars law. We need Congress to hold oversight hearings on this important process and we urge the FDA to release guidance as soon as possible that ensure patient safety, patient access to the right biologic medicines, patient choice and full transparency.” “Choice should be at the center of any decision to substitute or switch therapies and should only be decided by the patient and provider. Patient choice needs to be preserved and regulatory decisions must be based on sound science.” “Biosimilar regulations must put patient safety first. Policymakers and regulators must address appropriate patient safety and efficacy concerns as they relate to decisions around interchangeability, clinical indications, labeling, naming and substitution.”  Particular attention must be given to assure that rigorous clinical testing proves that a biosimilar works safely in each and every condition or disease for which it is approved to be prescribed, as well as in each distinct group of patients with that disease. 14