Do we finally have clarity on the regulatory process for more biosimilars to reach the market? Now that the FDA has approved its second biosimilar product Inflectra (infliximab) to market, will we see more biosimilar approvals in 2016?

Why were there no biosimilars for biologics in the past?

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Previously, there was no regulatory pathway for a biosimilar. Biologics typically are derived from living organisms. FDA broadly defines biologics as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cell and tissues. Biologics can provide unique challenges. They work by causing an immunologic reaction in the patient; different physiological responses may be seen, particularly among certain patient populations.

Biologics depend on living systems to produce products for market. Even tiny variations in the manufacturing process can significantly affect the finished medication and, most importantly, the way it functions in the body. “The product is a process.” A drug, by contrast, is a small molecule which is produced by chemicals. Once we understand the chemistry of a drug, anyone can produce it, thereby making generic drugs comparatively simple to regulate. However, biologics are large molecules which have been manipulated in some way and are impossible to replicate completely.

The cost of manufacturing a biosimilar is almost 100 times the cost of manufacturing a generic drug. The complexity of manufacturing a biologic requires a large, up-front financial investment for biosimilars compared to the small-molecule generic drug market. Biosimilar makers must essentially re-invent a production process, and then prove to the FDA that it results in a drug that is clinically the same as the branded product.

Will we see more biosimilars on the market?

If biosimilars provide the same benefit as biologics, surveys show the use of biosimilars would lower the cost of these medications as much as 40 percent and that competition from biosimilars would reduce total drug spending by approximately $25 billion over the next 10 years. There are still some outstanding federal and state regulatory issues, including whether biosimilars will share the same name with reference biologics and whether pharmacists in states will be able to automatically substitute interchangeable biologic products without unnecessary encumbrances.

However, there are several biosimilar applications pending at FDA and since the recent approval of the Celltrion/Pfizer biosimilar Jannsen’s Remicade, FDA may be under pressure to approve these pending applications. One of the concerns is how much data the FDA would require to establish the “no clinically meaningful difference” standard for 351(k) biosimilar applications.

Congress has been fairly critical of the pace at which the FDA is approving biosimilars and how Medicare plans to reimburse for biosimilar products. The FDA has begun to collect more money under the user fee program and that should provide the FDA with more robust funding for biosimilars. The Federal Food, Drug and Cosmetic Act, as amended by the Biosimilar User Fee Act of 2012, authorized FDA to assess and collect fees for biosimilar biological products from October 2012 through September 2017. FDA dedicates these fees to expediting the review process for biosimilar biological products.