Safe Substitution of Biologics

What is automatic substitution?1) Physician writes a prescription 2) 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

INTERCHANGEABLEBIOSIMILARS:

• 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• FDA Draft Guidance on Biosimilars wisely calls for more information before allowing interchangeability.

• May 11 hearing made it clear that the FDA’s draft guidance will proceed cautiously, but that there is pressure to speed up the process – especially with regard to interchangeability.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 NEVEROnly 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.

✓SOMETIMESFDA 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

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• 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.

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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

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• 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 hurdle02/20/2013 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 passesBy 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, 2013 12:00 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 2006

• 14 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

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What Do the EU and Canada Say About the Role of Physicians in Subtitution of Biosimilars?

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• The European Medicines Agency advises that the physician should be in charge of the decision to switch between the reference and biosimilar, or vice versa1.

• “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; 2012. Available from:

http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2009/12/WC500020062.pdf. Accessed November 6, 2012.

2 http://www.hc-sc.gc.ca/dhp-mps/brgtherap/applic-demande/guides/seb-pbu/01-2010-seb-pbu-qa-qr-eng.php

They understand the importance of physicans’ confidence in biosimilars.

In fact, NO EUROPEAN COUNTRY, OR CANADAALLOWS 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?

No risks specified Risks specified0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

80%

88%

% Very important or Critical

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?

85.9%

6.4%

4.3%0.8%0.5% 2.1%

Before the patient receives the medicine

Within 24 hrs after the patient receives the medicine

Within 1 week after the patient receives the medicine

Within 1 month

Within 3 months

No preference

• 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

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• 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

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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.