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The Biosimilars Challenge

Before tackling the dynamics of regulation and production, it seems fitting to set the table in showcasing the potential impact of generic biologics or biosimilars.

Whether it’s food, household items or pharmaceuticals, the economic times in which we live have led consumers to examine the value proposition of less expensive, off-brand substitutes or generic-equivalent offerings. While the differences between canned vegetables, frozen chicken nuggets and towels in these instances may be negligible, there are heightened concerns when turning one’s attention to pharmaceuticals.

While the generic equivalents for small-molecule chemical drugs have been embraced, their biologic cousins face some interesting challenges. Before tackling the dynamics of regulation and production, it seems fitting to set the table in showcasing the potential impact of generic biologics, or biosimilars.

For those requiring biologic drug treatments, the costs are much higher. For example, Avastin® is a cancer drug used with chemotherapy treatments that can cost more than $8,000 a month. Even with help from insurance this is obviously not a bill every patient is going to be able to pay. These costs add to the strain of an already taxed U.S. healthcare system and present an opportunity to hungry pharmaceutical companies still waiting for the next small molecule blockbuster.

Some estimates show more than 150 biologic medicines currently available, many of which have either lost patent protection or soon will. “The development of biosimilars at pharma companies is driven by the high revenue potential of these drugs and the patent expirations of existing biological medicines,” states Eugene Losev, group manager of strategic marketing at Baxter’s BioPharma Solutions business.

Projections for the size of the biosimilar market extend to nearly $5B within the next three to four years, with realized patient savings of between 20 – 50%, depending on the application. Although the patient need and potential business opportunity exists, the production and supply of biosimilars in the U.S. still offers challenges.

The Same, But Different

Currently, biosimilars are available in more than 10 countries around the world, including China, India and throughout Europe. However, there are none in the U.S. because only recently has the FDA provided the framework for an official approval process. Still, most are projecting that the appearance of a biosimilar in the U.S. is at least two years out, with only a handful of clinical trials currently in progress. The reasons behind such a delay illustrate one of the most challenging elements of working with biosimilars.

Unlike common small-molecule chemical drugs, biologics are molecularly much more complex. So this presents obvious challenges to contract manufacturers looking to emulate a substance when they don’t have access to the original developmental data. “It’s a new cell line and really an entirely new product requiring new processes and needing much more information up front,” offers Deepa Dahal, a principal consultant on Quintiles’ Biosimilar Intelligence Team, when discussing the differences between biosimilars and generic chemical drugs.

Additionally, the complex proteins that comprise biologics are derived from genetically modified living organisms, making them significantly more expensive than chemical drug ingredients. Not only are the materials more expensive but biosimilars also require a specifically designed pharmacovigilance plan for each product.

These elements of development and production have led to an FDA approval process that is product-specific in nature to help manufacturers ensure that their product emulates the role of the original biologic. “This can help lower the risk involved,” offers Quintiles’ Nigel Rulewski. “Basically, those companies that have the money to spend during the development stage to ensure their biosimilar matches the original biologic should face fewer issues in getting approval. On the small molecule side as many as one out of every 20 might not be approved by the FDA. With this process, as long as you’ve spent the money and done your homework in the beginning, the risk of not getting approved should be less.”

However, pharmaceutical processors will still need to tailor some of their internal approaches to match the demands of producing biosimilars. “Some CMOs may not be able to handle complex formulations or can handle only a subset of them”, offers Losev. “With some molecules, specialized expertise and equipment are required. In addition, not all CMOs are able to handle large commercial volumes that may be required.”

In addition to the investments in materials, developmental data and regulatory standards, the actual production presents additional challenges. “As an experienced fill/finish CMO, we see major differences associated with the handling of biological materials, which tend to be more sensitive,” offers Losev.

“Unique equipment investments are required to handle biologics. They could include disposable tanks and vessels, low temperature processing and storage, in-line mixing, specialized filtering systems and the ability to handle light and shearing sensitive molecules. In addition, some biologics require pre-filled syringes or cartridges. Equipment and process upgrades that increase yield are necessary for high-cost API products,” he continues.

“Additional processing hurdles can include temperature sensitivity, viscosity, light sensitivity, and shearing sensitivity. The API for biologics is also more expensive, so it’s important to have processes that optimize or increase yield and prevent material loss to keep costs down.”

The environment of developing biosimilars could also challenge the very profits many are seeking. “With development taking longer and demanding more financial resources, companies have to ensure they’re keeping pace with developments in patient care so that the biosimilars going through the development and approval stages won’t be out of date by the time they’re made available,” states Dahal.

Despite some of these challenges, the opportunity to tap into this growing market will be extremely appealing to many and, according to Rulewski, could provide some intriguing business theatre. “It will be interesting to see if price wars develop as pharmaceutical companies compete in these markets,” he states. “We might see just how much room there is in some of these segments.”