An Overview of Biosimilarity



Adam M. Brufsky, MD, PhD: Hello and thank you for joining this OncLive® Peer Exchange titled, “Emergence of Biosimilars in Oncology.”

In the year 2020, healthcare systems are expected to realize significant cost savings with the availability of 3 biosimilar drugs in oncology: rituximab, bevacizumab, and trastuzumab. There is great value in educating physicians about the use of biosimilars in clinical practice, as when providers understand the scientific rationale and justification, they can appropriately convey clinical messages to their patients and potentially help to streamline the process for increased biosimilar adoption.

I am Dr Adam Brufsky, MD, PhD, professor of medicine and associate chief of the Division of Hematology/Oncology at the University of Pittsburgh School of Medicine, and co-director of the Comprehensive Breast Cancer Center in Pittsburgh, Pennsylvania.

Participating today on our distinguished panel is Dr Kashyap Patel, CEO of Carolina Blood and Cancer Care, vice president of the Community Oncology Alliance, trustee and clinical affairs chair of the Association of Community Cancer Centers, and the medical director of the International Oncology Network in South Carolina.

In addition, this video series will include commentary by Dr Lee Schwartzberg, the executive director of the West Cancer Center, chief of the Division of Hematology/Oncology, and professor of medicine at the University of Tennessee Health Science Center, the medical director at the West Clinic, and the president/CMO at Vector Oncology in Memphis, Tennessee.

Thank you so much for joining us and let’s begin.

Lee Schwartzberg, MD, FACP: The best way to explain biosimilars is to start by explaining what a biologic is. A biologic is a medicine that is made in a living cell, and that’s very different from small molecule drugs, which are made through chemical processes and are easy to replicate.

A biosimilar is a new entity that is highly similar to the original or approved referenced biologic. Examples of biologics are antibodies, or antibody drug conjugates, things that are made in living cells and in very complicated molecules. The other thing about biologics is they’re not always the same because the basic structure is the same, but there are additions that are created in cells through this complex process, and there may be slight variations from batch to batch. So that’s very different from a generic, where every single molecule will look the same as every other single molecule.

That means that any biologic actually can vary from batch to batch. And over time, because of the conditions that it’s made in living cells, if they vary, or if the cell culture is different, or hundreds of other factors, each batch can be slightly different from one or another.

The FDA started approving biologics a few years ago, actually lagged behind Europe, which has been doing it for quite some time. And it is a complex process because it’s not showing that it’s structurally the same.

The FDA process for approving a biologic is different than what it is for approving an originator or reference product. Like any other new molecular entity, the originator product goes through the analytic steps to make sure the product is pure, doesn’t have reactivity with other things; it works in animals. But then there is a very lengthy clinical approval process, and that goes through the well-known phase I, II, and III process where first, safety is identified. Then small populations are tested, and finally there are 1, or usually multiple phase III studies, where a new product is tested against an old product to see if it is safe and effective. Those are the 2 criteria that the FDA uses for approval. That’s an originator. So if you think about it, it’s kind of an inverted pyramid. It starts with, you have the product. You make sure it’s analytically pure, it does what you think it does, do the pharmacology. But really what you’re doing is the clinical trials.

For a biosimilar it’s the exact opposite. It’s a true pyramid, where most of the work is done showing that the analytic purity and similarity to the originator is identical, and less work for the clinical process. Because if you show that the biosimilar is in fact highly similar to the originator product in terms of the way it looks, the product itself, its functional attributes, its pharmacology and its pharmacokinetics, then you can do fewer clinical trials. And to be honest, that’s really the whole benefit of biosimilars, that the expensive part of the process, which is doing these large clinical trials, doesn’t have to be done if you have a product that looks highly similar with only minor differences. Just like every batch of the originator looks somewhat slightly different. That’s what we’re looking for in a biosimilar.

Therefore, most of the work is done on showing the analytic similarities; multiple tests are done on the structure of the product, making sure the purity is correct, there are no impurities in it. Then looking at it in vivo, but in animal models, to make sure its activity and its functional attributes are highly similar to the originator. And then ultimately doing, in people, pharmacokinetic and pharmacodynamic studies to show that the drug is handled in a person’s body and a patient’s body the same way that the originator is. And then doing typically 1 clinical trial that is a large-scale trial to show that its efficacy and safety are equivalent, or noninferior. The actual term that’s used in these trials is an equivalence study. So statistically you have to show within a narrow range that the outcome is very similar between the biosimilar and the originator product. But the key difference is you’re doing only 1 large trial, and that suffices for the FDA to approve the drug to be used for the biosimilar the same way the originator is used, according to the FDA.

Biosimilars have to go through in their development a very rigorous quality assurance process. That looks at the way the drug is manufactured, and essentially scores of different analytic variables that have to be checked off to show that it is no different than the originator product. That’s where a lot of the rigor in the development of these molecules occurs.

Transcript Edited for Clarity

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