The FDA Pathway for Interchangeable Biosimilars

Ali McBride, PharmD, MS, BCOP, FAzPA, FASHP: The definition of interchangeability, and also the capabilities of what it means, was recently approved by FDA. The idea of interchangeability is that you can actually switch between the brand-name and biosimilar-based products without leading to any changes in safety or efficacy. Imagine you have a brand-name biologic A and a biosimilar B. The patient can change between A and B at any point in therapy on a consistent basis, and there will be no difference in outcome or safety and efficacy profile.

That becomes an important standing issue. What you’re saying is, the drug product has enough confidence, based on clinical studies, to show no difference. That really provides that extra layer of support to get there. There are already studies that have been done that actually have a similar-based biosimilar valuation when you’re switching between product A and product B, and the outcomes have no difference.

Whether those same companies will need to do added studies to address it will be an important question. In addition, there is the interchangeability status. The definition was just approved. Will companies go back and do extra studies, which will lead to higher costs? We don’t know. What we do know is the fact that you do have interchangeability will allow for the actual switching, the interchangeable switching, to occur between the biosimilar and brand-name products. That in itself will be very important. When it comes to oncolytics, I don’t think we actually have to worry about that too much. Supportive care will be of importance, but the therapeutic oncology therapies will usually be staying the same. So if you started on a biologic, the brand-name product, you’ll probably stay on that, unless there’s a patient relapse or other cases where you may switch.

When it comes to non-oncological therapy, like insulin—for example, when insulin becomes a biosimilar rather soon—that will be important to understand at the actual specialty pharmacy or pharmacy counter, because you’d be able to switch automatically, based on interchangeability designation. Therefore, the patient may switch it just as we’ve been doing for generics for many years.

What is the current availability of interchangeability based on designations? That is a great question, and the answer is, no. It’s actually a quick question for me. There are currently no biosimilars with interchangeability status. That’s important to know because we also have to understand that the FDA and interchangeability status, the actual document—which initially was draft document for almost 2 years—was finally finalized this year. If we’re looking to search for that, there was no means to do it because there was no pathway to the interchangeability status.

That also adds into other discussions, because over the last few years we’ve seen a large number of states that have new laws associated with biosimilar interchangeability. The United States has numerous laws, and each law is different based on the state. One could be as simple as actually having that understanding of a biosimilar within the EMR [electronic medical record] system, and that allows you to have an understanding of it.

In other cases, if you switch under a biosimilar, you have to notify the physician’s office. That can be a simple fax. If that does occur, will that fax even be sent to the physician? We don’t know, because many offices get 100, 200, 400 faxes a day. It may be compiled in a whole list of faxes. The interchangeable designation, the state laws, may have varied impacts. We do know the state legislation undergoing right now, but the actual initial guidance by the FDA allowed for the pharmacist to switch, based on interchangeability, without notification to the physicians.

We have a federal law, which says 1 thing. We have a state law, which says something else. So there may be some variation based on implementation, based on notification, and based on any type of measurements associated with states that do not make the physician or the prescriber aware of biosimilars or the biosimilar legislation. There’s a lot of important information going on at the state level, but right now we do not have interchangeability.

When we’re taking a look at the biosimilar safety and efficacy position across the board for a biologic or biosimilar, the FDA data indicate that there’s no difference in outcomes or adverse event profiles. That’s already been based on the clinical trials, or clinical trial. It’s also based on any other adverse effects, including immunogenicity, when we’re taking a look at those antibodies or looking at pharmacokinetic or pharmacodynamic capabilities with biosimilars, too.

In all these cases, those data have already been there. They’ve been supported, published, and provided to get that drug approved in those indications. So if you’re looking at the indications the biosimilar has been approved for in the sensitive populations or the extrapolation pieces, I think that understanding is well developed. In fact, that solidifies utilization of biosimilars here in the US [United States]. Don’t forget, the EU [European Union] has been doing this for almost 12 years now with biosimilars implementation. All we’re doing is piggybacking off those current indications.

The 1 thing that is new for both our sites is utilization of biosimilars in the curative setting for oncology. That changes the game much more than expected. Because when we’re switching, when we’re understanding the biosimilar cascade, there has to be confidence—which, again, is provided by the clinical trials but also by utilization—that a biosimilar will maintain that curative indication in those populations.

Kashyap Patel, MD: The safety and efficacy of biosimilars still need to be taught, and I’ve been speaking about biosimilars for the last 2-and-a-half, 3 years. There’s been a slow uptake happening, but still there’s a lot more education that has to be done because physicians are too busy, and the technology and development of the new drugs is outpacing our capacity of absorbing all the information. The manufacturers have to do a lot more in providing education about the new path for the biosimilar, the totality of evidence, the safety, the efficacy, and immunogenicity.