• Biologics: Also known as biologic agents, biologics are any of a wide range of powerful FDA-approved medications bioengineered from any of a wide variety of living organisms or their components. Containing proteins that target and modify natural intracellular and cellular responses, biologics are generally both expensive and complicated to purify, process, and produce, but have greatly expanded treatment options for a variety of specific disorders. In the past 20 years, biologics have become a cornerstone in treating diseases including rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, irritable bowel syndrome, and inflammatory bowel disease (IBD).

• Biosimilars are prescription biological agents that are highly similar to an already approved biologic medication, also known as the “reference product” or “reference biologic.” The minor differences between a biosimilar and its reference biologic reflect the complex nature of these agents and the different production methods involved. However, biosimilars act in a similar way to their reference biologics, with no clinically meaningful differences in effectiveness, safety, or treatment routine, and they are approved using the same standards of pharmaceutical quality, safety, and efficacy used for all biologic medicines.

• Reference Products, or “reference biologics,” are the already approved biologic medications against which a proposed biosimilar is compared to ensure that it is highly similar and has no clinically meaningful differences.

• Interchangeable Products are biosimilars that can be substituted for the reference product without the involvement of the prescriber. While pharmacy laws and practices vary from state to state, pharmacists can substitute an interchangeable product for a reference biologic without a health care provider writing a prescription specifically for that biosimilar. To be approved for interchangeability,  the U.S. Food and Drug Administration (FDA) requires evidence that: 1) interchangeable products produce the same clinical result as the reference product in any given patient, and 2) switching patients more than once between the biosimilar and reference product is both safe and effective. Currently, none of the FDA-approved biosimilars for inflammatory bowel disease (IBD) have been approved by the FDA for interchangeability.

Yes. The Food and Drug Administration (FDA) requires biosimilars to meet rigorous approval standards to assure that they are as safe and effective as their reference biologic. These standards were established through the Biologics Price Competition and Innovation Act (BPCI Act) of 2009, which created an abbreviated licensure pathway for biological products shown to be biosimilar to or interchangeable with an FDA-approved biological product. The act was passed to provide more treatment options, increase access to lifesaving medications, and potentially lower health care costs.

While there can be minor differences between biosimilars and their reference biologic (such as a different buffer or stabilizer), there are no clinically meaningful differences between them. It is important to remember that even biologics have minor lot-to-lot differences between them by nature, and these differences are carefully controlled and monitored for both the biosimilar and its reference biologic.

No. Biosimilars and generics do have a lot in common. Both are versions of “brand-name” drugs that can offer patients more affordable treatment options. And both are approved through special abbreviated pathways designed to avoid duplicating costly clinical trials. However, there are important differences.

Generics are small molecules with an active ingredient that is structurally and therapeutically identical to that of an original brand-name medicine. They must be identical to the brand name medicine in terms of active ingredient, strength, dosage form, and route of administration, although inactive ingredients can differ; they must also be “bioequivalent” (i.e., has the same rate of and extent of absorption) as the brand name drug based on serum drug levels.

In contrast to most synthetic medications made from chemicals, biologic medications cannot be exactly copied because they are made from living sources. For that reason biosimilars are similar (but not identical) to their reference biologic. Manufacturers of biosimilars must therefore provide extensive information to prove that that their product is “highly similar” to the reference product except for minor differences in clinically inactive ingredients.

Manufacturing biologics results in unavoidable variations that are not seen in the development of small molecule drugs because these agents are unusually large, complex, and derived from living sources. Thus, there are inevitably slight differences between manufactured lots of biologics, as well as between biosimilars and their reference biologics. These variations are normal and expected, but they mean that no two lots are identical. That is why the FDA controls for within-product variations of both biosimilars and biologics using rigorous assessment and control strategies that ensure for consistent safety and clinical performance. Because there are no clinically meaningful differences in terms of safety, purity, and potency between biosimilars and their reference products, they are said to be “highly similar” rather than identical in nature.

Not necessarily. If a reference drug is proven to be safe and effective for one indication (disease or condition), the FDA generally allows approval to be “extrapolated” for all the other approved uses of the originator (reference) drug. Occasionally, however, only a subset of indications will be approved. Fr example, a manufacturer may still have an unexpired patient for a specific indication that precludes granting approval for that particular indication by a biosimilar.

Generally speaking, however, if the FDA has already approved a reference biologic approved to treat a variety of conditions, the FDA will approve the biosimilar for all the other conditions as well, even without specific studies involving patients with those conditions. Thus, if a reference biologic is approved to treat rheumatoid arthritis, plaque psoriasis, ulcerative colitis, and Crohn’s disease, a biosimilar proven to be safe and effective in treating just one of these conditions (e.g., plaque psoriasis) can be used to treat the other conditions already approved for the reference biologic (rheumatoid arthritis, ulcerative colitis, and Crohn’s disease) as well.

Your health care provider can check a prescribing information to determine approved indications for any biosimilar you are prescribed.

While biosimilars and their reference biologic are equally safe and effective, biosimilars provide more treatment options and can potentially lower treatment costs and increase access to care. Biologics are extraordinarily expensive: While fewer than 2% of Americans use them, they represent about 40% of all prescription drug spending and cost an estimated $2.5 billion to develop. A recently published analysis by the RAND Corporation estimated that form 2017-26, biosimilars could reduce direct spending on biologic therapies by $54 billion.