Safe Substitution of Biologics

What is automatic substitution? 1) Physician writes a prescription2) Pharmacist is allowed, or required, to provide a different medicine to the patient X

What Does The Law Say About Interchangeability? Biologics Price Competition and Innovation Act, Section (351)(i)(3) ‘‘(3) The term ‘interchangeable’ or ‘interchangeability’, in reference to a biological product that is shown to meet the standards described in subsection (k)(4), means that the biological product may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.

Congress defined 2 different levels of biologic copies INTERCHANGEABLE BIOSIMILARS: HIGHLY Similar SAME EFFECT in any given patient is EXPECTED NO ADDED RISK from switching BIOSIMILARS: HIGHLY Similar

FDA is Proceeding Cautiously with Biosimilars FDA Draft Guidance on Biosimilars wisely calls for more information before allowing interchangeability. May 11 hearing made it clear that the FDA’s draft guidance will proceed cautiously, but that there is pressure to speed up the process – especially with regard to interchangeability.

Is biologic substitution [no doctor involvement] scientifically appropriate? X NEVER Only Similar. FDA has not approved as safe for substitution. Highly Similar but … Not expected to have same effect in any given patient Not determined to have the same risk if patient is switched. ✓ SOMETIMES FDA has determined safe for substitution Highly Similar Safe effect in any given patient No greater risk if switch vs no switch OK to switch UNLESS Dr. has specified no switching

ASBM Interchangeability Recommendations made at FDA May 11 Hearing 7 Thorough evaluation and understanding of biosimilar before designation as “interchangeable” Only biosimilars determined to be “interchangeable” should be substituted

Who decides if substitution is allowed? Congress said “interchangeable” means switching without physician involvement. FDA determines if a product meets the criteria for “interchangeable” – this is a scientific decision. States historically have decided what pharmacists are allowed to do. ≠

States Are Crafting Their Own Substitution Policy Under pressure to control health costs amid tight budgets, States are creating biosimilars policy that would allow AUTOMATIC SUBSTITUTION of a prescribed biologic with a biosimilar by an insurer, pharmacy, or other third party, PROVIDED Physician is notified after the substitution has occurred. Opponents of PHYSICIAN NOTIFICTION point to the EU as a model for use of biosimilars to control costs.

Early Indications From States 10 Lack of uniformity - likelihood of a patchwork approach. Cost pressures great. Likely there will be some states where PHYSICIAN NOTIFICATION after a substitution has occurred may not prevail. Biosimilar drug bill clears hurdle 02/20/2013 SALT LAKE CITY — A local lawmaker’s push to help facilitate the introduction of biosimilar drugs to the Utah market has cleared a key committee hurdle. SB 78, sponsored by Sen. Stuart Adams, R-Layton, received a favorable recommendation in a Senate committee Wednesday and now advances to the Senate for further review. ' Biosimilar' drug bill passes By Lloyd Dunkelberger, Herald-Tribune / Tuesday, February 19, 2013 TALLAHASSEE- The battle over biosimilar drugs moved ahead today in the Florida House, as the Health Quality Subcommittee approved a bill that would create standards for using a new wave of pharmaceutical products that are expected to gain in popularity in the next few years. Gewanter: Legislation would protect patients taking complex meds Thursday, January 24, :00 am BY HARRY GEWANTER The treatment of many serious and chronic medical conditions has been changed dramatically by a class of cutting-edge medications called “biologics.” These medications have produced clinical miracles for thousands of children and adults with arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, cancers and other diseases. Instead of facing death or significant disability, biologics have changed the course of these diseases and allowed patients to continue to work, attend school and have a more typical life.

Learning from Biosimilars Data from the EU Biosimilar pathway established 2003, First biosimilar approved in approved by January 2013 Modest savings Slow market saturation Smooth and steady rollout, emphasis on physician education Expected savings in US market could be low initially 11 EU Experience In 2004, the European Union (EU) became the first jurisdiction in the world to authorize a formal regulatory pathway for biosimilars. The statuary and regulatory provisions have been adopted over time through a public and scientific process and now the EU's rigorous guidelines, requirements, and experiences provide an instructive reference to the United States and other regions.

What Do the EU and Canada Say About the Role of Physicians in Subtitution of Biosimilars? 12 The European Medicines Agency advises that the physician should be in charge of the decision to switch between the reference and biosimilar, or vice versa 1. “Health Canada does not support automatic substitution of a Subsequent Entry Biologic for its reference biologic drug and recommends that physicians make only well- informed decisions regarding therapeutic interchange.” 2 1 European Medicines Agency. Questions and Answers on Biosimilar Medicines (Similar Biological Medicinal Products). London: European Medicines Agency; Available from: Accessed November 6, They understand the importance of physicans’ confidence in biosimilars.

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

Biologic Substitution: The Physician’s Perspective

A Physician’s Guiding Principles Patient safety is paramount. Information is power: the more we know, the better for patients. Manufacturers’ accountability. Hippocratic Oath: “first, do no harm”

Survey Results: Importance of Notification of Medication Switching: With and Without Known Risks Question: How important would it be for you to be notified by the pharmacist that your patient has received a biologic other than the one you prescribed …if you were aware that the product could cause an unwanted immune response in some patients or that small differences between brands could have clinical implications for patients? Survey of 376 physicians who prescribe biologics

Preferred Timeline for Notification (n=376) Question: At what point would you prefer to be notified of a change in the biologic medicine dispensed? Respondents held clear preferences for their timelines for notification. About 85% would prefer to be notified “Before the patient receives the medicine.”

Our message to the FDA: when balancing potential Cost Savings against Patient Safety… …Safety must always win.

“Dispense As Written”: The Physician’s Reaction to Pressure and Interference 19 Rushing biosimilars into use before rigorous quality data over time or interchangeability determination undermines physician confidence in biosimilars. Cutting physicans out of the treatment decision, or overruling them creates an incentive to prescribe “Dispense as Written”. Thus, paradoxically, utilization of biosimilars (and any potential cost savings) will actually be undermined by rushing biosimilars into the market and cutting physicians out of the loop.

Promoting Use of Biosimilars: The Right Way 20 QUALITY leads to CONFIDENCE leads to UTILIZATION: Establish safety and quality through CLINICAL TESTING and aggregate DATA OVER TIME. From EU approval to first biosimilar was 3 years, they currently have 14. (US approval of first biosimilars likely in 2014). This will increase physician confidence in the quality of the product. The EU Worked WITH Doctors: Did not countermand physician’s medical orders by switching patients’ medication from biologic to biosimilar. Instead, promoted the value prescribing quality biosimilars INITIALLY.

The EMA Biosimilar Substitution Policy Adheres to ASBM’s Four Pillars: PRIORITIZING PATIENT SAFETY over cost savings, speed, or politics. LEVERAGING WHAT WE HAVE LEARNED from the EU’s science-based approach. PROMOTING PHARMACOVIGILANCE: holding manufacturers accountable for the quality of their product. KEEPING DOCTORS RELEVANT: Physicians and their patients should determine treatment, not a third party.

For BIOLOGICS and BIOSIMILARS to provide long-term benefits to patients around the world, Quality and Confidence must be assured via strong GLOBAL STANDARDS that prioritize patient safety, hold manufacturers accountable for their product, and keep treatment decisions in the hands of physicians.