1. U.S. and European Physician Perspectives on Biosimilar Naming and Substitution Michael S. Reilly, Esq. Executive Director, Alliance for Safe Biologic Medicines Presented at the Food and Drug Law Institute 57 th Annual Conference April 23, 2014 Washington, DC

2. ASBM 2010 ASBM formed to provide STAKEHOLDER GUIDANCE to FDA in development of US Biosimilar Pathway STEERING COMMITTEE composed of physician and patient groups, runs day-to-day operations. ADVISORY BOARD: Composed of Physicians, Researchers, Pharmacists, and Patients from around the world. Serves as resource on the science and clinical use of biosimilars, guides our policy recommendations. 2 STEERING COMMITTEE

3. Brazil United Kingdom Brussels, Belgium Madrid, Spain Dusseldorf, Germany Versailles, France South Africa Edmonton, Canada Kunming, China Ankara, Turkey Msida, Malta Madras, India Netherlands Venezuela Porto, Portugal ASBM Serves as a Resource for People Around The World Who Wish To Learn More About Biosimilars…

4. “The Four Pillars” PRIORITIZING PATIENT SAFETY LEVERAGING WHAT WE HAVE LEARNED PROMOTING PHARMACO- VIGILANCE KEEPING DOCTORS RELEVANT ASBM’S GUIDING PRINCIPLES

5. ASBM Has Conducted a Number of Surveys PROVIDES EMPIRICAL DATA regarding regarding perspectives on these new medicines by those most familiar with their clinical use. – U.S. Prescriber Survey (September 2012) – U.S. Pharmacist Survey (October 2013) – E.U. Prescriber Survey (November 2013)

6. Timeline: European Prescriber Survey March 18, 2014 European Prescriber Survey Results Formally Released in Brussels OCT NOV DEC JAN FEB MAR APR October-November 2013 European Prescriber Survey Conducted by Industry Standard Research November 21, 2013 European Prescriber Survey Results Previewed at DIA Biosimilars Workshop in Dublin APRIL 8, 2014 ASBM Presents European Prescriber Survey Results at 58 th INN Consultation

7. 7 Goal of the WHO’s INN Programme: Ensuring the Medicine Prescribed is the Medicine Received. ASBM has twice presented its survey findings to the WHO to aid in the development of international naming standards for biosimilars: U.S. Prescriber Survey results presented at the 57 th Consultation on International Nonproprietary Names (INN), October 22, 2013 European Prescriber Survey results presented at 58 th INN Consultation, April 8, 2014. ASBM has been asked not to discuss the particulars of this meeting, pending publication of the INN’s Executive Summary.

8. 8 DISTINGUISHABLE NAMES WHO has attempted to move from “do we need biosimilars to have distinguishable names?” to “what form would a distinguishable name take?” A shared root with a “biological qualifier” has been proposed. NATIONAL REGULATORY AUTHORITIES Currently there is a patchwork of naming standards by the NRAs of the world- some using distinguishable names, some not using them, and some with no consistent policy. A voluntary global standard requires that they cooperate. Challenges Facing the WHO

9. Benefits of the Proposed BQ System For countries whose National Regulatory Authorities have STRONG pharmacovigiliance systems, adopting the BQ would provide an ADDITIONAL SAFEGUARD to avoid a single point of information failure. While potentially redundant, our survey data indicates that prescribers do not in fact always record all the required data when reporting adverse events. For countries whose National Regulatory Authorities have WEAK pharmacovigiliance systems, adopting the BQ will provide a valuable international framework for clarity and patient safety.

10. Support for the Biological Qualifier among NRAs Proposed at 57 th INN, October 22, 2013 Proposal has the support of representatives from Japan and Australia, which have or are developing their own BQ standards, but expressed willingness to conform with the global standard. EMA thought it unlikely that a biological qualifier would be adopted in Europe but did not rule it out. FDA has indicated its support for distinguishable names, as in the case of tbo- filgrastim, but have not issued any formal policy for biosimilar naming. ✓ ✓

11. 11 Prescribing by INN: Encouraged, even Required in Much of the World REQUIRED by NRAs in China, Colombia, Latvia. ENCOURAGED by NRAs in India, Netherlands. PROPOSED as requirement in Russia. Formerly REQUIRED in Greece and Romania, but since revoked in favor of using brand name. In many countries, it is at the DISCRETION of the prescriber whether to use INN or brand name.

12. How Distinguishable INNs Aid in Pharmacovigilance IDENTIFICATION Patients, physicians, and pharmacists should be able to accurately identify the product, ensure it is the intended prescription, and avoid inadvertent substitution. A biosimilar should be distinguishable both from its reference product and from other approved biosimilars which reference the same biologic. PHARMACOVIGILANCE Distinguishable naming helps differentiate products for observing and reporting adverse events. Track and trace of biologics is more challenging than with chemical drugs. Adverse impact may go unrecognized in patients for months. Multiple means of product identification avoid a single point of information failure. MANUFACTURER ACCOUNTABILITY Patient response must be traced to the correct manufacturer’s product.

13. European Prescriber Survey 13 First large-scale survey on biosimilars in Europe. Examined physician knowledge and prescribing practices. Conducted by Industry Standard Research, October-November 2013 15-Minute Web-based Survey 470 Prescribers distributed equally between 5 countries in Western Europe: France Germany Italy Spain United Kingdom Roughly equal distribution between six specialties in which biologics are frequently prescribed.

14. E.U. Prescriber Survey: Familiarity Level with Biosimilars 14 54% possess only a “basic understanding” of biosimilars Only 22% consider themselves “very familiar” with biosimilars 20% have heard of them but cannot define 4% have never heard of them

15. 15 European Prescriber Survey Same Nonproprietary Name = Structurally Identical? “If two medicines have the same non-proprietary scientific name, does this suggest to you or imply that the medicines are structurally identical?” (N=470) 53% of respondents mistakenly believe biosimilars with identical non-proprietary name as its reference biologic is structurally identical to that reference biologic.

16. 16 European Prescriber Survey Same Non-proprietary name = Same Indications? “If two medicines have the same non-proprietary scientific name, does this suggest to you or imply that the medicines are approved for the same indications?” (N=470) 61% of respondents believe biosimilars with an identical non- proprietary name as its reference biologic is approved for the same indications, which may not be the case.

17. 17 European Prescriber Survey Identifying Biologic Medicines in Patient Record Only 32% of respondents use brand name and non- proprietary name (INN) to identify the exact biologic being prescribed. 24% use INN only, which could result in patients receiving the wrong medicine.

18. 18 European Prescriber Survey: Reporting Adverse Events 17% report only the INN. Identical INN for two different medicines can result in pooling of adverse events, false attribution and other difficulties.

19. European Prescriber Survey: Batch Number Inclusion 19 27% of prescribers NEVER include. 33% only SOMETIMES include. 40% ALWAYS include. “How often do you include the batch number when reporting adverse events?” (N=470)

20. What do Physicians Say about Biologic Substitution?

21. Industry Standard Research21 European Prescriber Survey Results: Importance of Prescribing Authority “How important is it to you to have the sole authority to decide, together with your patients, the most suitable biologic medicine for their disease?” (N=470)

22. Industry Standard Research22 European Prescriber Survey Results: Importance of DAW Authority “In a situation where substitution by a pharmacist was an option in your country, how important would it be to you to have the authority to designate a biologic medicine as ‘DISPENSE AS WRITTEN’ or ‘DO NOT SUBSTITUTE’?” (N=470)

23. In fact TODAY NO EUROPEAN COUNTRY, OR CANADA ALLOWS Automatic Substitution: AUTOMATIC SUBSTITUTION

24. France: Limited Substitution 24 ELEMENTS OF THE LAW: Recognizes the difference between chemical and biologic medicines (not identical copies). Pharmacist informs prescriber of substitution Requires record-keeping of substitution Substitution can be permitted by physician CONCERNS: Creation of a 2-tier system: “naive patients” are given a different standard of care than patients prescribed existing biologics.

25. Summary: Key Findings of Surveys 25 There is a need for further education about biosimilars among physicians. The current “patchwork approach” of each NRA developing its own naming system is not adequate to ensure that patients receive the medicine prescribed by their physician. Distinguishable nonproprietary names are important to practicing physicians, and it is our hope that this will be useful to WHO in crafting a global standard that will improve safety for patients worldwide. It is important to physicians to retain the authority to use “do not substitute” to ensure the patient receives the correct medicine.