Briefing Report: Biosimilars - Coming to a Pharmacy Near You... At Some Point

Wednesday, April 3, 2013


Sometime in the next couple of years, a new class of biotechnology drugs known as “biosimilars” is expected to become available to U.S. consumers.  Patents on a number of major branded drugs are scheduled to expire in the coming years, fueling the desire of many generic and brand name drug companies to bring the first biosimilar version of each branded drug to market.  However, because biological products are complex, the development and approval of biosimilars is proving to be a time consuming process.  This process is being watched closely by some of the largest pharmaceutical companies in the world—as well as pharmacies, physicians, and other interested stakeholders.  While there is debate surrounding exactly when the first biosimilars will appear on the U.S. market, some estimate these drugs will be available as early as 2014.  In response, California has recently joined the list of states that will soon be considering legislation to regulate these drugs.

This briefing report is intended to serve as a primer for the debate that is playing out in California and at least 15 other state legislatures across the nation.[1]  Potentially at stake is healthcare savings for consumers and profits for some drug companies, depending on how each state decides to handle the wave of biosimilars that could replace critical name brand biologics used to treat cancer, rheumatoid arthritis and multiple sclerosis.

Bio What?

To understand the debate that is taking place in statehouses throughout the U.S., one must first figure out what is meant by a few key terms:

  1. Biological product: According to the Food and Drug Administration (FDA), “[B]iological products include a wide range of products including vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and proteins.  Unlike most traditional, small-molecule prescription drugs made through chemical processes, biological products are generally made from human and/or animal materials.  Biological products are usually larger than and have a more complex structure than small-molecule prescription drugs.  Such products may be manufactured through biotechnology, derived from natural sources, or, in some cases, produced synthetically.”[2]

  2. Biosimilar: The FDA defines a biosimilar as, “…a biological product that is highly similar to a U.S.-licensed reference biological product notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.”[3]  Since biologics are produced in living cells, biosimilars and originator biologics are unlikely to ever be completely identical to each other, hence the reason why the generic versions are called “biosimilars.”[4]

  3. Interchangeable: An “interchangeable” biological product is biosimilar to the originator biological product, and can be expected to produce the same clinical result as the originator product in any given patient.  If administered more than once to an individual (as many biological products are), the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the originator product without such alternation or switch.

How We Got Here

The Patient Protection and Affordable Care Act (ACA), was signed into law by President Obama on March 23, 2010.  Among its provisions, the ACA contained a provision (Section 7002) amending the Public Health Service Act to create an abbreviated licensure pathway for biological products that are demonstrated to be “biosimilar” to or “interchangeable” with an FDA licensed biological product.  Under this new law, a biological product may be demonstrated to be “biosimilar” if data show that, among other things, the product is “highly similar” or “interchangeable” to an already-approved biological product.[5]

Since passage of the ACA, the FDA has been establishing standards for licensure to ensure the safety and effectiveness of biosimilars.  In February 2012, the FDA released draft guidelines adding details to the original proposal for introducing biosimilar drugs.  This was followed by the Biosimilar User Fee Act of 2012, signed into law in July 2012, which allows the FDA to assess and collect fees for biosimilar products from October 2012 through September 2017.  These fees will help the FDA further develop the biosimilars approval process and improve its efficiency and reproducibility.[6]  To date, it is not clear when the biosimilar guidelines will be finalized.  However, it is important to note that the federal biosimilar law prohibits the FDA from delaying action on a biosimilar application simply because it has not yet issued relevant guidance.[7]

Are Biosimilars Available Now?

Although the FDA has yet to approve a biological product as biosimilar or interchangeable, several companies are developing biosimilar products and they are expected to submit applications for licensure under the new law soon.[8]

While the U.S. is still working on its approval pathway, biosimilar drugs have been available in Europe for close to a decade.  The European Medicines Agency (EMA) created an approval pathway for biosimilars in 2004, publishing guidelines in 2005.  The EMA approved its first biosimilar in 2006.  To date, the EMA has approved 14 biosimilars in Europe, although two have been withdrawn since approval.[9]

Other countries are focusing on biosimilars as well, including, but not limited to, Brazil, Russia, India, China, Saudi Arabia, and South Korea.[10]

Legislative Landscape

While the FDA regulates which drugs will be approved, the individual states govern the practice of pharmacy including drug substitution laws.  As such, legislation is being proposed in a number of states to update state drug substitution laws to include biosimilars.  Current California law governing generic pill substitution does not define biosimilars.  As a result, many feel state codes need to be updated right away to ensure that when the FDA approves interchangeable biosimilars they will be able to be substituted at the pharmacy level.  With no legislation at all, biosimilars will still be allowed to be prescribed by physicians but pharmacists will not be able to substitute them for brand products at the retail level.  Opponents, however, view the biosimilar legislation as an attempt to pre-empt the FDA on biosimilar products.

In California, two different bills have been introduced on the topic.  The first, AB 1139 (Lowenthal) authorizes a pharmacist filling a prescription order for a biological product subject to the Federal Food, Drug, and Cosmetic Act, to select a biosimilar product, as defined by federal statute, provided that product is deemed by the federal Food and Drug Administration to be interchangeable with the prescribed product.  There doesn’t appear to be any objection to limiting substitution to drugs declared interchangeable by the FDA, which is currently all that is being proposed by AB 1139.  Once the FDA makes that determination, however, there is debate as to what substitution practices are appropriate.

SB 598 (Hill) builds upon the provisions proposed in AB 1139 (Lowenthal), by mirroring existing state law concerning generic pill substitution and adding a provision that requires a pharmacist to enter information about the substitution into the patient record system or notify the physician within five days after a substitution is made.  SB 598 also requires the Board of Pharmacy to maintain a current list, if available, of biosimilar products determined by the FDA to be interchangeable.[11]

Let The Debate Begin

Supporters of SB 598, and of many of the bills being debated nationwide, feel that such measures are needed to protect patient safety and ensure a full and complete patient record.  They say biosimilars will present new challenges that have not been seen with generic medicines because of their difference in size, structure and the manufacturing process.  They point out that the manufacturing process requires extensive genetic expertise, and argue it is also prone to errors, justifying the need for continuous testing and control.  Proponents believe the after-the-fact notification to a physician’s office and the record-keeping requirements are important safeguards to have in place so that the patient’s medical record is updated to reflect the exact medicine that went into the patient’s body in the event there is an adverse reaction to a biosimilar product.

Opponents, however, feel these provisions are being promoted by drug companies that want to impede the ability of the market to develop less expensive options of some important medications.  They feel the provisions are designed to restrict the ability of pharmacists to substitute biosimilars for brand name products.  Specifically, they believe requiring a pharmacist to notify the doctor if a switch is made and requiring that records of the switch be maintained for years will deter pharmacists from substituting a biosimilar product, thereby limiting the use of biosimilars that could save patients, and taxpayers big money.  The Generic Pharmaceutical Association points out that the limits “…don’t sound too onerous but undermine confidence in these drugs and are burdensome.”  Opponents point to FDA Commissioner Margaret Hamburg’s remarks in February 2013 that attempts to undermine trust in biosimilars is "worrisome and represent a disservice to patients who could benefit from these lower-cost treatments.  Substitutability helped spur the growth of the generic(s) industry and is similarly essential to help foster competition in the biological drug market.  Ultimately, such competition will spur innovation, improve consumer choice and drive down medical costs."[12]

Moving Forward

There is no agreement on when the United States will enter the biosimilar marketplace, however, once biosimilars are introduced they are forecasted to increase access to valuable new therapies and reduce costs.  While cost-savings estimates vary, some believe allowing biosimilars could save billions of dollars.  Pharmacy-benefit manager Express Scripts believes that “…copies of a handful of key drugs could save the nation $70 billion over 10 years.”[13]  It will be the job of lawmakers to balance these potential cost savings with patient protections when California, and the United States, eventually begins to open the door to these new biological medicines and manufacturers.

For more information on this report or other Business, Professions & economic Development  issues, contact Amber Alexander, Senate Republican Office of Policy at 916/651-1501.

[1] Bills Pending in Other States. Background Information for SB 598. Office of State Senator Jerry Hill. March 2013.
[2] Information for Consumers (Biosimilars). November 2, 2011. Food and Drug Administration.
[3] Information for Consumers (Biosimilars). November 2, 2011. Food and Drug Administration.
[4] Trusheim, Mark R, Aitken, Murray L and Berndt, Ernst R. Characterizing Markets for Biopharmaceutical Innovations: Do Biologics Differ from Small Molecules? 2010, Vol. 13, 1, pp. 1-45.
[5] Information for Consumers (Biosimilars). November 2, 2011. Food and Drug Administration.
[6] Biosimilar User Fee Act (BsUFA). November 1, 2012. Food and Drug Administration.
[7] H.R. 3590, Section 7002 (a)(8)(C) Biologics Price Competition and Innovation Act of 2009 of the Patient Protection and Affordable Care Act.
[8] Information for Consumers (Biosimilars). November 2, 2011. Food and Drug Administration.
[9] McCamish, Mark and Woollett, Gillian. Worldwide experience with biosimilar development. Mar-Apr 2011, Vol. 3, 2, pp. 209-217.
[10] Elvidge, Suzanne. Facing Up to the Biosimilar Challenge: Preclinical and Beyond.”  Fierce Biotech.  January 2013.
[11] SB 598 Fact Sheet. Background Information for SB 598. Office of State Senator Jerry Hill. March 2013.
[12] Dr. Margaret Hamburg, FDA Commissioner. Generic Pharmaceutical Association Conference. JW Marriot, Orlando, Florida. 25 February 2013.
[13] Rockoff, Jonathan D., Weaver, Christopher and Whalen, Jeanne. Biotech Drugs Still Won’t Copy.  Wall Street Journal.  27 Feb. 2013: B.1.