No Clinically Meaningful Difference: The Upward Trend of Biosimilars

No Clinically Meaningful Difference: The Upward Trend of Biosimilars

October 31, 2017PAP-Q4-17-FA-001

Innovation Feature: Innovation for Quality, Cost & Competitive Advantage – Introduction

Keeping up with quality is key for the industry throughout the supply chain. Quality must be ensured from the earliest phases of development, always with an eye toward manufacturing. It is almost taken for granted that a drug product will be produced without any defects, and following all GMP regulations — often times meeting more than one governing agency’s requirements. However, the road to perfection in manufacturing is not necessarily without issue. In spite of these challenges, quality remains the goal — and it is with this goal in mind that innovation happens.

Innovation is driven not only by the need to improve, but also to create difference. The drivers of innovation in pharma and biotech range, though in each case manufacturers must keep an eye toward quality. A happy byproduct of innovation is a firm competitive advantage. Not only does innovation improve process, quality and patient outcomes, it shows a company that can demonstrate effective innovation will likely outperform other organizations.

There are endless developments happening in all phases of the industry — and these developments are more than exciting. The industry is on a precipice, and from now until the next decade is when these advances may finally launch. From immuno-oncology to wearable devices in clinical trials and even an entirely new way to manufacture, we are more than on the verge — we are dangling over the future’s edge.

Innovation Feature: Innovation for Quality, Cost & Competitive Advantage – Part 1

Following a string of approvals, biosimilars are positioned to go the way of generics.

Biosimilars are defined as having no clinically meaningful difference from the biologics reference product, though they are not necessarily “interchangeable.” The legislation encouraging the production of biosimilars was solidified through The Patient Protection and Affordable Care Act (Affordable Care Act) signed into action by former President Obama in 2010. Biologics indeed get special mention, via the Biologics Price Competition and Innovation Act (BPCI Act), which states that a biosimilar can only be a biosimilar if data and trials prove the drug is “highly similar” to a biologic drug product already on the market.1 The act thus explains that biologics are only allowed minor differences and therefore must not diverge in safety or pose any additional risks than the original biologic.1  This act also made the path to becoming a biosimilar easier — as long as the drug is not clinically different from the biologic, a biosimilar is not considered its own original entity and does not have to go through with a full approval timeline; much like generics for API drugs, the only standard is to meet the requirement of equivalency and serve as a copy of the biologic in question.2

There are 50 distinct biosimilars poised to enter the market within the next five years, and these are positioned to create a great deal of competition in the marketplace.

Biosimilars by Name

Of course, questions still loom. For instance, how can healthcare providers keep informed on biosimilars and recognize when they should be substituted for the biologic? The FDA has answered this with their Nonproprietary Naming of Biologic Products, which is a guidance for the industry.3 The guidance states: “the nonproprietary name designated for each originator biological product, related biological product, and biosimilar product will be a proper name that is a combination of the core name and a distinguishing suffix that is devoid of meaning and composed of four lowercase letters.” However, as of the publish date of the guidance, interchangeable products were still not given a suffix format convention. The agency’s recommendation for the suffix of all biologics, whether original, related or biosimilar, is that all follow the same set of “shoulds.”

The main takeaway of the guidance is that the naming should be unique and not meant to be misleading or confusing to the user. A chief recommendation is that no suffix can be “too similar” in either look or name. It should not “be capable of being mistaken for the name of a currently marketed product (e.g., it should not increase the risk of confusion or medical errors with the product and/or other products in the clinical setting),” nor should it “Look similar to or otherwise connote the name of the license holder.”3

Taking this into consideration, it is clear that the FDA is paving the way for biosimilars, and that although only minor differences are allowed (which do not affect the overall performance or efficacy of the drug product), they must be independent in other ways so as not to confuse the market with being an existent product. The first biosimilar to be approved in the US was Zarxio (filgrastim-sndz) manufactured by Sandoz, Inc. Zarxio can be prescribed for the same indications as Amgen’s Neupogen, which was originally licensed in 1991.4 Speaking on the breakthrough approval of the nation’s first biosimilar, FDA Commissioner Margaret A. Hamburg, M.D., noted on March 6, 2015, “Patients and the health care community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy and quality standard,” and that “biosimilars will provide access to important therapies for patients who need them.”

Almost exactly a year following, the agency approved the second biosimilar, with the goal of providing more treatment options to more people and increasing accessibility to affordable care. Inflectra (infliximab-dyyb), manufactured by Celltrion, Inc., is a biosimilar to Janssen Biotech, Inc.’s Remicade (infliximab), which passed through the FDA on April 5, 2016. Again, Leah Christl, Ph.D., Associate Director for Therapeutic Biologics at the FDA, highlights the fact that a biosimilar is not a replica of the biologic: “A biosimilar is not an exact duplicate of another biologic; rather, a biosimilar is highly similar to the reference product.”5 Driving the point home that this is likely the future of pharma and the way we take drugs, Christl emphasizes the growth potential for biosimilars. “Biosimilars are likely to create greater competition in the medical marketplace,” she notes. “This could not only increase treatment options for patients but also lead to less expensive alternatives to comparable products. With an increasing number of biosimilars on the market, consumers may expect to get equally safe and effective treatment, but at lower costs,” says Christl.5

Biosimilars Ease into the Pharmacy  

It is likely that biosimilars will not only fill a gap in the healthcare system as being a lower cost alternative, but that as more drugs shift toward patent expiry territory, these will be considered go-to drugs. Not only will that increase competition in the market, but this competition is sure to fuel greater innovations. In a Supreme Court decision on June 12, 2017 (just over two years from the passing of the first biosimilar in the US), a unanimous decision was reached to confirm that manufacturers do not need to wait the typical six months after FDA approval to begin manufacture.6 In the opinion, Justice Clarence Thomas wrote, “An applicant may provide notice of commercial marketing before obtaining a license.”7 This has the potential to speed up the process of patient accessibility greatly; the waiting time from approval to manufacture becomes nil with this new measure. The ruling shook up the industry, with mixed opinions coming from all sides; however, Stephen Hanauer, MD, Professor of Medicine at Northwestern University in Chicago, summed up the money-making potential of the decision for the industry, noting: “Six months of marketing is a lot of money for a billion-dollar drug,” he continued. “This will affect the economics of the pharmaceutical industry.”8


The potential for capital is further clarified when looking at the market for biosimilars as a whole — namely, the projected growth and product value over the next ten years. According to health information technologies and research firm QuintilesIMS, this space is poised for incredible growth in the US. The company predicts that the global biologic medicines market will exceed $390 billion by 2020 and account for up to 28% by value of the global market for pharmaceuticals.9 This growth is predicted to create more choice and greater treatment options. Also according to QuintilesIMS, “Over the period 2016-2020, some 225 new active substances (NAS) are expected to come to market globally.” Of these, based on trends over the last 20 years, approximately 30% will be biologic in nature.9 Spending has no sign of slowing down, either. The firm predicts a highly steady growth rate, with “global spending on medicines expected to grow at a compound annual growth rate of 4%-7% over the same period, to reach up to US $1,430 billion” by 2020.

It is likely that biosimilars will not only fill a gap in the healthcare system as being a lower cost alternative, but that as more drugs shift toward patent expiry territory, these will be considered go-to drugs.

A key to sustaining the growth of the biosimilar market is the embracing of competition, facilitated by government. There are 50 distinct biosimilars poised to enter the market within the next five years, and these are positioned to create a great deal of competition in the marketplace.9 However, for patients to fully reap the benefits of biosimilars, the competitive landscape must be embraced as part of the culture of innovation, progress and development. The challenge of biosimilars coming to market is directly related to government, as the national healthcare costs will be reduced. QuintilesIMS projects the United States, Germany, France, Italy, Britain and Spain will save as much as $110 billion by 2020, approximately, because of biosimilars entering the mainstream.9

Ready to Manufacture

According to the 2017 Nice Insight Contract Development and Manufacturing Survey, 33% of respondents whose business is engaged in the development of biologics are involved in the manufacture of biosimilars. Of those, 17% outsource biosimilar production to contract service providers. The US is behind the EU curve when it comes to biosimilars, and may need to go into overdrive during the coming years in order to make up for lost time. There are 32 biosimilar products approved for use in patients in Europe, based off of 12 biologics, as compared to the five in the US.10 Furthering the trend, interchangable biosimilars are expected to be produced within the next two years. 11

Innovate or Die

It’s an exciting time for the industry, and the reason for that excitement is mainly innovation. Whether the driver is cost, quality or just trying to find a solution that doesn’t yet exist, the marketplace stands to benefit from an influx of new ideas, better answers and improved processes. The firm that is able to capture this innovation wave will not only come out ahead — a byproduct of innovation is competitive advantage — but will also be able to claim a greater social good, as these lifesaving therapies reach the table almost as soon as they are approved. Keeping this in mind, it’s best to get out of the way of innovation, for there is little that can be done to stop it.   

Read Part 2: Moving Beyond Monoclonal Antibodies



  1. Information On Biosimilars. U.S. Food and Drug Administration. 10 Mar. 2010. Web.
  2. From Our Perspective: Biosimilar Product Labeling. U.S. Food and Drug Administration. 11 Jan. 2017. Web.
  3. Nonproprietary Naming Of Biological Products: Guidance For Industry. U.S. Food and Drug Administration. Jan. 2017. Web.
  4. FDA approves First Biosimilar Product Zarxio. U.S. Food and Drug Administration. 6 Mar. 2015. Web.
  5. Biosimilars: More Treatment Options Are On The Way. U.S. Food and Drug Administration. 28 Aug. 2017. Web.
  6. Zachary Brennan. “US Supreme Court: No Six-Month Wait For Biosimilars After FDA Approval.” Regulatory Affairs Professionals Society. 12 Jun. 2017. Web.
  7. Sandoz Inc. V. Amgen Inc. et al. Supreme Court Of The United States. 12 Jun. 2017. Web.
  8. Damian McNamara. “Supreme Court Ruling On Biosimilars Will Lower Drug Costs.” Medscape. 17 Aug. 2017. Web.
  9. “Delivering On The Potential Of Biosimilar Medicines: The Role Of Functioning Competitive Markets.” IMS Institute For Healthcare Informatics. Mar. 2016. Web.
  10. Simon Wentworth. “Are We On The Verge Of A Biosimilars Breakthrough In The USA?” The Pharma Letter. 22 Aug. 2017. Web.
  11. Zachary Brennan. “FDA: Interchangeable Biosimilar Approvals Expected Within 2 Years.” Regulatory Affairs Professionals Society. 26 Jun. 2017. Web.


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