Manufacturers of biosimilars realize that the US market comprises roughly 60% of global pharmaceutical revenues. Therefore, the US Food and Drug Administration’s regulatory standards weigh heavily on the minds of pharmaceutical executives. For companies that sell or intend to sell their biosimilars on the global market, they must adhere to the standards of regional and local regulators, at significant cost.
A panel discussion of experts at the Festival of Biologics 2023 meeting last week in San Diego tackled this challenging issue: Global harmonization of standards will likely be a principal factor shaping the future of biosimilars.
Real-World Evidence to Provide Confirmatory Data
One of the greatest regulatory challenges for biosimilars, said Aaron Josephson, Director, Regulatory Policy & Intelligence, Teva, “is the lack of harmonization globally.” Without it, “[pharmaceutical companies] have to spend money, resources, and time to meet the requirements of every regulatory region, and those costs add up quickly,” he said during a panel discussion.
Mr. Josephson commented, “Real-world evidence can be leveraged, to create a different paradigm for evaluating biosimilars. We can rely on the analytical data to provide reasonable assurance of effectiveness. Let’s use the data collected elsewhere in the world to provide the confirmatory data.” He suggested this might be directed by a global consortium or by the World Health Organization.
Gillian Woollett, DPhil, Vice President and Head of Regulatory Strategy and Policy, Samsung Bioepis, added that global reference products already exist. “The pivotal trials of the reference product are the same. We need the same for biosimilars. However, several countries still require country-specific data. Yet, the science is the same among countries.”
This doesn’t just apply to late-stage clinical trials. “Even the [pharmacokinetic] study requirements from one country to another can be a barrier,” added Leah Christl, PhD, Executive Director, Global Biosimilars Regulatory Affairs, Amgen. “Yet, the science is the same among countries. Any additional barrier is a cost of access. Some countries cannot afford that additional barrier.”
Avoiding Unnecessary Human Studies
Dr. Woollett asserted, “The science has done what it should do. When we already have the analytical results, what is the residual uncertainty? What will clinical studies actually tell us at that point? We shouldn’t be experimenting on human beings if we don’t have an important question to answer.”
Moving away from later-stage clinical investigations is not so simple, according to Sandy Yan, MD, PhD, Head of US Regulatory Affairs, Hengenix Biotech (Shanghai Henlius). Dr. Yan, who had also worked at the FDA, reminded that no biosimilar has the exact fingerprint of the biologic. She doesn’t think there will be a single decision, which allows for the elimination of clinical studies in biosimilar evaluations.
Dr. Christl agreed that although there will always be differences analytically between molecules, the question is whether these differences will result in outcomes differences. “We have confidence in certain types of products,” she said, “but biologics are only going to get more complex. We have to be flexible. FDA has always been flexible. The switching studies are not a requirement (across the board).”
What are we seeking to understand when we require the clinical study? Dr. Woollett asked. Will this significantly change the regulatory risk or the decision to approve or not approve the product?