Interchangeability and Postmarketing Pharmacovigilance of Biosimilars

Hope S. Rugo, MD: Interchangeability is an interesting area. Extrapolation is much easier because that means that you’ve got a biosimilar that was approved in the neoadjuvant or metastatic setting and can use it, alternatively, in the other setting. For example, if you’re testing a biologic growth factor like filgrastim or pegfilgrastim, if it worked in 1 setting, it’s going to work across other settings. I think that everybody’s been able to embrace that much more easily compared to the drugs that are being used for therapeutic purposes to treat cancers.

There’s growing acceptance that this extrapolation is reasonable, but interchangeability is different. You can switch from the reference to the biosimilar at any time. Interchangeable means that there is little difference. The pharmacist who’s filling the prescription can decide which one they’re going to provide you, based on the criteria—what the insurance requests, what’s cheaper, what they bargained for, et cetera—to get a better group price.

So that would be interchangeability. They don’t have to come back to the provider and say, “You ordered the branded trastuzumab. Can I give this biosimilar instead?” If it’s an interchangeable product, the pharmacist can change.

As described by the regulatory agencies, interchangeability is complex because it requires studies that show that you can switch from one to the other and then back again without changing immunogenicity or safety. Obviously you’re not going to be able to look at efficacy well in that setting. It really hasn’t been studied in any appreciable way for the therapeutic anticancer drugs, and I don’t know that it really will be something that happens in the community. In the United States, pharmacists will generally have to ask, “Can we use the biosimilar?” Much of that will be decided by insurers and by negotiations between our infusion centers and drug providers, in terms of which agent is being provided at a lower cost.

Cornelius F. Waller, MD: Manufacturers go to the regulatory agents when they start production of these biosimilars and ask for guidance either by the FDA or [European Medicines Agency, EMA]. Part of this guidance, after the physical chemical analyses and safety and purity issues, and then based on phase 1 and phase 3 data in patients, is that the manufacturer has to present thorough pharmacovigilance and a safety program that takes place after approval of the drug. As a manufacturer, you have to assure that the production is not being changed because then, in a way, you produce your own biosimilar of what you have produced before and you have to follow certain guidelines to assure that the quality is not changing.