Myths and Misconceptions on Biosimilars

Common myths and misconceptions for biosimilars are explored.

Anthony Mato, MD, MSCE: I want to switch gears and talk about myths and misconceptions that you’ve heard about from biosimilars. We can start with Tim and then jump around. One myth is “Each biologic lot is a biosimilar of itself.” I certainly heard that there’s an anti-CD20 monoclonal antibody, rituximab. We’ve been using biosimilars already.

Tim Peterson, PharmD, BCOP: This is an interesting point, and this brings up something I don’t think we’ve necessarily touched on, and that’s the phenomenon of product drift. A lot of people who probably would make this comment would be referring to product drift—changes in the processing and manufacturing that can happen in rituximab, for example. For rituximab, there can be changes in the processing and how they manufacture it. It can cause changes in, what Bhavesh referred to earlier, the antibody-dependent cellular cytotoxicity, which can actually change over time. This has been very well documented for Herceptin [trastuzumab], in particular where Herceptin was compared with a biosimilar and actually the biosimilar had higher ADCC [antibody-dependent cellular cytotoxicity] activity than the referenced product.

Anthony Mato, MD, MSCE: On some level, if it’s too high, then it is no longer a biosimilar.

Tim Peterson, PharmD, BCOP: You can’t have that either. It needs to be neither inferior nor superior. It sounds counterproductive. If it’s superior, maybe they would want it.

Anthony Mato, MD, MSCE: Then it’s a different drug.

Tim Peterson, PharmD, BCOP: Exactly, then it’s a different drug. I would say, just based on the presence of product drift within 1 particular class, it’s not a biosimilar clearly because we have our quality-assurance pathways with the FDA. Any change in any manufacturing practices, they need to report data that show that there are no significant effects with regard to the purity, the potency, and the safety of those medications. Actually, that process continues to improve and get more involved now that there’s more understanding of this phenomenon of product drift.

Anthony Mato, MD, MSCE: OK. Marc, take this one. The myth is “Lack of indication by FDA means you can’t use that biosimilar even if the biologic is used for that indication.”

Marc Earl, PharmD, BCOP: That’s caused a lot of questions in the white blood cell growth factor space. It didn’t have an indication there, especially in the bone marrow transplant conditioning space. As I mentioned earlier, we should go back to the science perspective and try to understand if you think there would be any issues in this space. Also, do you believe in the biosimilar approval process? That’s where I try to head back to when I get this question.

I try to look to other organizations that we talk about—the NCCN [National Comprehensive Cancer Network] as well. And even if it doesn’t have an indication, get their thoughts on if we still think this drug is appropriate there. We have tried to have this conversation with our physicians and our pharmacists, again through the P&T [pharmacy and therapeutics] committee, to have a multidisciplinary discussion and see if we agree with that. If we agree, then we would go ahead and use that product without an indication if we thought it had coverage. If we had concerns, we would stop. We would not automatically interchange and force that process.

Anthony Mato, MD, MSCE: OK, this is the last 1 we will discuss. I think you’ve already talked on this, Bhavesh: “Interchangeability requires higher quality standards than the biosimilar.”

Bhavesh Shah, RPh, BCOP: Sure. I’ll talk about interchangeability, the extra requirements the FDA has, and put a little light on what that means. For interchangeability, the FDA requires the manufacturers to do multiple pharmacokinetic and pharmacodynamic studies.

Basically, you have to have a washout period. Then you switch the patient, and then you have another washout period. There are about 3 different changes, and at each time point they’re looking at immunogenicity, pharmacokinetics, and pharmacodynamics in the different patient populations. They’re looking to see if there are any changes, if the patients change back and forth multiple times. I would say it requires a significant amount of uplift for manufacturers to do this, so no one has actually done this.

But it doesn’t actually mean that if a provider thinks, “Hey, I’m going to switch this patient from this biosimilar to this biosimilar,” there are any issues with interchangeability. I believe there’s a misconception that you can’t change the patient from 1 part to another because it doesn’t have a changeability status, that there are nonmedical switches that usually happen a lot across the world. Interchangeability is a regulatory term. People need to understand that, and that it’s not a clinical term.