By Anna Rose Welch, Chief Editor, Biosimilar Development
In the biosimilar industry, there have been what could be considered “legendary” occurrences that have both turned heads and buoyed this industry’s spirit and drive to succeed. One of these is the seemingly mythical but real story of Norway’s great biosimilar transition. It’s impossible to read an article or attend a biosimilar conference without at least coming across references to the country’s success. The U.S. Supreme Court’s decision to side with the biosimilar industry on the Amgen vs. Sandoz patent dance skirmish was a triumph, as well.
But if we were to step back and focus on the individual company level, the entrance of biosimilars and development of the market has offered companies unique leadership opportunities. And though I find myself impressed by the varying efforts of several companies to progress both their biosimilar businesses and the industry as a whole, there is one company that stands out to me as earning “legendary” status. That company is Samsung Bioepis.
In February 2017, I found myself in Philadelphia interviewing a now-former VP at Samsung Bioepis. We were celebrating a milestone in the company’s existence — it’s fifth anniversary — by discussing the company’s efforts to establish its process innovation. It was this process that enabled the company to have three biosimilars approved in Europe, two submitted for EMA review and one for FDA review — all in five brief years. In two articles, I highlighted the company’s process — in particular, the use of quality “toll gates,” Quality by Design (QbD), and unique risk-management techniques — and the importance of in-house training to share the company’s “lessons learned.”
Now, a year later, the company has seen all of its biosimilars under European review approved, and a majority of them have been launched, including Europe’s first Herceptin biosimilar. In the past year, the company also announced its partnership with Takeda to co-develop novel biologics. So, when I realized Brian Hosung Min, an SVP and head of drug substance at Samsung Bioepis, would be presenting at the World Biosimilars Congress in San Diego in May of this year, I jumped at the opportunity to see how far the company and its process innovation has progressed. Over lunch before his eighteen hour flight back to South Korea, Min discussed the company’s ongoing efforts to realize a lower cost-of-goods sold (COGS), speed up production, and manage risk in biosimilar and novel biologics development.
Technological Innovation: It’s Not All About Trends
Though five products approved and/or marketed in six years may already be lightning-fast for a small biotech, Samsung Bioepis has no intention of slowing down. As Min highlighted, the company currently has 120 bioreactors running 24/7 at close to 100 percent capacity. And in order to quickly develop and receive approval for a number of its biosimilar candidates, the company carried out numerous experiments in parallel.
“The more we can do to reduce the cost of development and manufacturing, the better we can transfer the cost savings to patients or payers through lower prices and be more competitive,” Min said. “We’re always thinking about this — it’s a mindset.”
Thanks to this mindset, the company has set some ambitious future goals to reduce the COGS. The company’s ultimate goal is to establish a successful micro scale-down model. Even those of us who aren’t manufacturing experts are likely familiar with the scale-up process, through which batch sizes are increased as the drug progresses successfully from laboratory into clinical development. But a scale-down model, on the other hand, is a small-scale model that embodies the large-scale commercial process. Not only is an efficient scale-down model critical for improving process understanding, but it ultimately protects a company from quality problems and failure upon reaching commercial scale.
As Min explained, “We can use the information gleaned from a small scale model to predict the quality and operating conditions and prepare for any variabilities when we reach a larger production scale.” (I like to think of this as extrapolation, but this time in the manufacturing world as opposed to the prescribing world.)
Samsung Bioepis’ GMP production scale is 15,000L. They are currently using a 2L scale-down model, but the hope is to work down to a micro-scale high-throughput system (HTS). “We’re not quite there yet,” Min added. “But in making the scale-down model even smaller, we would be decreasing overall development cost by reducing the amount of raw materials needed, as well as the number of people that are needed to run each experiment. With an even smaller scale-down model, we can run more experiments which, theoretically, should mean we gain more data, and, in turn, greater knowledge of the process to make our product similar.”
The use of scale-down models may not be novel in the realm of biologics. After all, the need for predictive scale-down modeling in process validation has been discussed in guidances from the FDA and the International Conference on Harmonization (ICH). But the emphasis placed on this practice varies depending on the company and the therapeutic focus. “All of these technologies and tools are available to everybody — innovators and biosimilar developers,” he described. “But, from my experience, how you handle that technology is different.”
As an example, Min points to how these technologies are used for innovator products compared to biosimilars. For one, it’s no secret that biosimilar process development is more scientifically challenging to accomplish than that of an innovative drug. For an innovative drug, the manufacturer evaluates many processes and selects the most efficient one. However, there is no need to match another developer’s science or product. The need to match is where the biggest challenge arises in biosimilar development (hence, the critical need for tools like scale-down models). For a biosimilar company, such as Samsung Bioepis, these types of tools aren’t just a new, nifty scientific toy to add to a lab; they’re critical to ensuring the science can be successfully scaled up so the biosimilar’s critical quality attributes match those of the originator.
When I asked Min which future trends in manufacturing he was keeping his eyes on, he reiterated the fact that all the tools you can want or need are available, but it’s how you choose to use them. While there are some newer technologies — for instance disposable technologies — that are turning heads, they will likely be only game-changing for certain products. Larger-volume drugs like etanercept, which are in high demand and have a lower purification yield, will be much better suited for larger stainless tanks, he explained. Disposable technologies will be more important for projects that require only 1,000 L as opposed to 15,000 L. “For those projects, it of course makes sense to use disposable technology,” Min said. “But these types of things to me are not trends, per se. We just need to pick and choose which project will be a good fit for the various tools at our disposal.”
A New Era: Balancing Novel Biologics Ambitions And Biosimilars
Indeed, it’s these types of questions that are the biggest things on Min’s mind —“Where can we succeed and what is the right thing for us to do?” he shared. And these questions are likely to continue as the company faces its entrance into the innovative drug development space.
Choosing to start with biosimilars instead of innovative biologics — the opposite decision of many leading players today — is a good example of Samsung Bioepis' dedication to risk management. “Every biosimilar we’ve launched so far has been first or second to market,” Min said. “This could be attributed to many things, but risk management has been key.”
He explained that, the company has embedded the lessons learned and its technical capabilities into what it refers to as its Agile Biologics Development Platform. Moving forward, the company intends to leverage this platform for the development of novel biologics. Min says the lessons learned through biosimilar development will go a long way to helping the company mitigate cost overruns and time delays — the two biggest issues plaguing novel drug development.
Last fall, Samsung Bioepis and Takeda announced a new joint collaboration to work on multiple novel biologics, starting with a treatment for acute pancreatitis. This partnership will be particularly important in helping Samsung Bioepis learn about the unfamiliar aspects of novel drug development — for instance, choosing targets and developing a pipeline.
“Making a deal with Takeda is another form of risk management for us, because they know how to do the early stages of development,” he said. “If we can apply what we know about downstream process development and manufacturing, we can help each other, so we’re eventually able to go through the whole process on our own.”
Though the company rose to success rapidly as a biosimilar pure-play, Min clarified it was never the plan to have biosimilars be its only business. “From day one, our long-term goal was to become a leading biopharmaceutical company,” said Min. “It was never our intention to remain solely focused on biosimilars. We are in the biosimilar business for the long haul, and biosimilars will continue to serve as our foundation.” Meanwhile, the company hopes the steps it has taken towards novel biologics development will set the stage for long-term growth.
Min emphasized that the “hunger” mentality which propelled the company to biosimilar success will likely remain instrumental going forward. “There are a number of reasons we’ve been able to do all that we have over the past six years. The most important among these, however, is the people. If you strip away the science, technology, and business strategy, at the very core is our dedication and blue-collar work ethic to become the best at what we do.”