Biosimilars: Hard to make but lower costs

From biologics to biosimilars 

The processes used to make both biologic and biosimilar drugs are so complex that it is impossible to create an exact duplicate substance. As a matter of fact, it is considered normal for there to be differences between batches and even between doses from the same manufacturer.^{11, 12}

This is a very real dilemma for biosimilars.

U.S. biosimilar rules are complex, confusing

The simplest way to grasp the unique complexity of the U.S. approach to biosimilars is to compare it to that used in the European Union and other countries.

Broadly speaking, both U.S. and European Union (EU) regulators must certify that biosimilars are as safe and effective as their reference products. But the crucial difference is that EU regulators consider all their approved biosimilars to be interchangeable. If the biosimilar has been proven to be as safe and effective as its reference product, it is treated the same way as an approved generic drug.¹⁵

But in the U.S., the U.S. Food and Drug Administration (FDA) may find that a given biosimilar is safe, effective and clinically indistinguishable from its reference product. But that does not make a biosimilar interchangeable. Instead, U.S. law has established a separate approval pathway for any biosimilar drug that wishes to be considered interchangeable.¹⁶

Remember: The FDA has already certified that the biosimilar is as safe and effective as its originator. But to achieve interchangeable status, biosimilar makers must provide additional data demonstrating that switching between the reference product and the biosimilar does not cause additional risk. The goal is to make sure that clinical outcomes and safety stay the same even if patients are repeatedly switched between the reference product and the biosimilar.¹⁷

This added level of scrutiny might seem harmless. There’s no such thing as being too safe, right?

But in fact, it amounts to a brand-new approval process that has created confusion and hesitation among prescribing physicians in the U.S.¹⁸ That confusion is one part of the reason why biosimilars lag far behind generic drugs in terms of numbers prescribed.

The doubts and misunderstandings about biosimilar interchangeability lead to lower prescription rates and fewer substitutions in the U.S.¹⁹

The American Society of Clinical Oncology believes that, where oncology generic drugs would typically achieve around 75% - 90% market share in the first two years of approval, biosimilars for cancer have significantly underperformed in terms of uptake.²⁰

A recent report noted the relatively slow adoption of oncology biosimilars in the U.S. market. This report referenced some of the points mentioned here. In particular, oncologists report having a limited understanding of the biosimilar manufacturing process. This leads to concerns over safety and efficacy from potential variations in the product, and this contributes to a lack of clarity around interchangeability.²¹

Moving beyond oncology, a different study showed that over half the physicians in specialties with high rates of biosimilar utilization (rheumatology, gastroenterology, and dermatology), do not believe in the safety or efficacy of biosimilar medications.²²

We know that interchangeable biosimilars could contribute to improved biosimilar uptake. Why? Because they would be easy to prescribe and physicians would be more confident in their use.²³

But what are some of the practical steps that could help bring this about?

Have more biosimilars available

It could help to simply have more biosimilars available. Recently, biosimilars have started gaining FDA approval in larger numbers. In fact, by July of 2024 the FDA had already approved a record number of biosimilars for a single year.²⁴ Hopefully this will permit more physicians to gain experience and confidence in their use. 

Provide physicians with greater awareness

Physicians need greater awareness of what biosimilars are, and how they are made and tested. For example, it may help them to know that biosimilars have been used in nearly 2.7 billion days of patient therapy since 2015. During that time there have been no meaningful differences in safety or clinical outcomes from their reference products.²⁵ 

End the interchangeability designation

Perhaps the simplest move would be to end the separate interchangeable designation entirely. Interestingly, the Biden administration’s 2025 budget proposes exactly that. It would eliminate the two-tiered approach by ending the interchangeability designation.

As such, all approved biosimilars to be interchangeable with their reference biologic.²⁶

Commenting on the proposed shift, the American College of Rheumatology notes that removing the interchangeability designation “…is more uniform with current scientific understanding, as well as with the methodology implemented by other regulatory jurisdictions, such as the European Union.”²⁷

Notably, legislation to end the two-tiered approach has received bipartisan support in the U.S. Senate.²⁸

In general, competitive markets are good for everyone, and biologic drugs are no exception. Biosimilars have the potential to save billions in costs for clients, patients and the system at large.

Anything that can be done to improve the simplicity and ease of substituting brand name biologics for their matching biosimilars should be encouraged. Interchangeability can play a key role in this effort.