Ever wish you could replicate the taste of that $200 bottle of wine that has been aged to perfection over the past four decades? This task is a near impossibility, as it requires you to replicate things like environmental, harvesting, and storage conditions. Many of these things, like weather, can’t be replicated, yet even very minor changes can mean the difference between an incredibly tasty wine and expensive vinegar.

The difficulty in replicating very finicky, precise conditions is one currently shared by a class of drugs called biologics. You can think of biologics as the “fine wine” of pharmaceuticals, many of which are approved for the treatment of diseases that no other drug can treat, including various types of cancer, arthritis, Crohn’s disease, and many others.

As the patents for some of these biologics have started to expire, pharmaceutical companies endeavor to replicate them as “generics.” These drugs are extremely complex and making an identical, “generic” version is like replicating a fine wine—it’s nearly impossible.

This complexity has launched the development of a new class of drugs, called biosimilars. As the name might suggest, biosimilars are not exactly identical to brand-name biologics, but are, well…similar. Biosimilars are still fairly new in the US—the FDA approved the first biosimilar in 2015—and there are still a lot of unanswered questions.

Answering basic questions such as “what are biosimilars?” and “what are the pros and cons of biosimilars?”, as well as understanding the challenges of biosimilars manufacturing, can help life science marketers when working with patients and companies involved in the development of biosimilars.

Biosimilars 101: What Are Biosimilars and How Do They Compare to Biologics?

So, what are biosimilars? To really understand them, you must first consider the processes by which biologics are made and how they differ from simpler pharmaceuticals, often called small-molecule pharmaceuticals. Take a well-known small-molecule pharmaceutical like aspirin: it has a small and simple chemical structure (21 atoms) and can be easily constructed by chemists in a lab or factory with relatively simple starting materials. This makes it (relatively) easy to copy. As with many other small-molecule pharmaceuticals, once they are off-patent, many manufacturing companies do make copied versions. These identical copies are called generics and there are a lot of benefits to developing them, which include undergoing an abbreviated FDA review process and reduced costs to patients, up to an estimated 80 to 85% less.

In contrast to small-molecule pharmaceuticals, biologics are way clunkier and their synthesis, much less straightforward. Chemists can’t synthesize these drugs, and as their name would suggest, biologics are made in living organisms, like bacteria, yeast, or animal cells. With some slight engineering tricks introduced in a laboratory, scientists can coax these single-celled workhorses into constructing biologics for them.

But, as discussed above, this process is finicky and minor changes in the manufacturing process can alter the molecular structure of the biologic, which in turn, can translate to clinical differences in both safety and efficacy. Any company looking to copy a biologic will have to replicate the exact manufacturing process for the brand-name biologic. These intricate, technical details are not often publicized and a company will have to spend a significant amount of time investigating different manufacturing processes and using complicated bioanalytical techniques to confirm bio-identity. In some cases, the techniques to confirm exact molecular identity don’t exist.

Therefore, the best that many drug companies can hope for is to produce a similar drug, with similar efficacy and safety. Thus, the biosimilar is born.

From Development to Pricing: Issues With Biosimilars

Because biosimilars are distinct from generics, they have a distinct development and FDA approval pathway. Biosimilars are evaluated on a case-by-case basis and certain biosimilars may require additional pharmacokinetic or immunogenicity testing. While the FDA has developed specific guidelines for biosimilar drug development, certain aspects of biosimilar development have come under fire. Development issues with biosimilars and the related pros and cons of biosimilars for both patients and companies include:

Pros of Biosimilars

  • Pricing: Due to the abbreviated approval process that the FDA requires for biosimilars, these drugs are typically less expensive, by approximately one-half in some cases.
  • Increased treatment options: Approval of biosimilars create additional treatment options for often expensive brand-name products. These options are good for patients, as there may be manufacturing problems with a given biologic, in which case, having an approved biosimilar option can help patients continue treatment.

Cons of Biosimilars

  • Indication extrapolation: Some biosimilars may get approval for certain indications that the reference product (i.e., brand-name biologic) was approved for, without having to run a duplicative clinical trial. This may be dangerous for patients and some studies have shown that there is a 30% chance that a patient will experience an adverse event when taking a new biologic, let alone a biosimilar.
  • Efficacy and safety: While biosimilars go through clinical testing, they may not have identical efficacy and safety and thus, are not interchangeable. Some studies have found that biosimilars have very different efficacy from their reference product. Because these are complex molecules, there are also additional potential safety issues that may be caused by immunogenicity.

Given the new nature of biosimilars, there are still many efficacy and safety questions to be answered. One of the larger hurdles for biosimilars use is that the decreased price of the drug is not reaching patients, due to refusal by some insurers to cover biosimilars. With nine biosimilars currently approved by the FDA, many more under review, and large pharmaceutical companies like Pfizer, Sandoz, and Amgen investing in biosimilar development, better understanding of and solutions for these issues are sure to emerge.

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