How copies of complex biologic drugs are making treatments more accessible
A quiet revolution has been unfolding since 2015—one that promises to make life-changing treatments more accessible while maintaining the same rigorous safety standards.
In the world of medicine, a quiet revolution has been unfolding since 2015—one that promises to make life-changing treatments more accessible while maintaining the same rigorous safety standards. This revolution is powered by biosimilars, nearly identical versions of complex biologic drugs that have reached the end of their patent protection. For patients with conditions ranging from cancer to rheumatoid arthritis, these drugs represent both hope and affordability in an often expensive healthcare landscape.
Biological medicines, or "biologics," are unlike traditional chemical-based drugs. They're large, complex molecules produced from living organisms—everything from bacteria to animal cells—using sophisticated biotechnology 3 . Think of them as microscopic biological factories designed to perform specific functions in the body.
When these biologics lose patent protection, biosimilars can enter the market. But a biosimilar is not simply a generic copy—the manufacturing process is far more complex. While generic drugs are chemically identical to their reference products and relatively simple to produce, biosimilars are highly similar to their reference biologics but not exactly the same 3 .
This distinction arises because living organisms naturally introduce minor variations—much like how two baker's batches of sourdough might have slight differences despite using the same starter.
Why does this matter? The complexity of biologics means they can be 200 to 1,000 times larger than conventional chemical drugs, with intricate three-dimensional structures that are impossible to replicate exactly 3 . Instead, biosimilar manufacturers must demonstrate through comprehensive testing that their products have no clinically meaningful differences from the reference product in terms of safety, purity, and potency 3 .
| Characteristic | Biosimilars | Generics |
|---|---|---|
| Molecular Size | Large, complex molecules (up to 270,000 Da) | Small, simple molecules (up to 300 Da) |
| Production | Produced using live organisms; 5-9 years development; High cost | Chemical synthesis; 2-3 years development; Lower cost |
| Structure | Highly similar to reference product; same amino acid sequence | Structurally identical to reference medicine |
| Regulatory Focus | Comparability studies focusing on similarity | Bioequivalence studies |
Complex molecules derived from living organisms with inherent variability. Require extensive analytical, nonclinical, and clinical studies to demonstrate similarity.
Simple chemical compounds with identical structure to reference product. Primarily require bioequivalence studies to demonstrate therapeutic equivalence.
The United States established its legal framework for biosimilars with the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), creating an abbreviated approval pathway that acknowledges the unique nature of these products . The first biosimilar, Zarxio (filgrastim-sndz), wasn't approved until March 2015, illustrating the careful approach regulators have taken 2 .
The FDA requires biosimilar developers to provide scientific evidence demonstrating that their product is highly similar to an already-approved FDA biological product (the "reference product") 1 .
Extensive comparison of the physical, chemical, and biological characteristics
Evaluation of toxicity, pharmacokinetics, and immunogenicity
Human trials to demonstrate similarity in safety, purity, and potency 3
The FDA has issued numerous guidance documents to help manufacturers navigate this process, covering topics from "Comparative Analytical Assessment" to "Postapproval Manufacturing Changes" 1 .
The period from 2015 to 2018 marked the dawn of the U.S. biosimilars market, with a growing number of approvals that expanded treatment options across therapeutic areas. These early entrants paved the way for today's robust biosimilars market.
| Biosimilar Name | Approval Date | Reference Product | Therapeutic Area | Manufacturer |
|---|---|---|---|---|
| Zarxio | March 2015 | Neupogen (filgrastim) | Prevention of infection during cancer treatment | Sandoz |
| Inflectra | April 2016 | Remicade (infliximab) | Rheumatoid arthritis, Crohn's disease, other inflammatory conditions | Pfizer |
| Erelzi | August 2016 | Enbrel (etanercept) | Rheumatoid arthritis, plaque psoriasis, other inflammatory conditions | Sandoz |
| Amjevita | September 2016 | Humira (adalimumab) | Multiple inflammatory conditions | Amgen |
| Renflexis | May 2017 | Remicade (infliximab) | Multiple inflammatory conditions | Organon |
| Cyltezo | August 2017 | Humira (adalimumab) | Multiple inflammatory conditions | Boehringer Ingelheim |
| Mvasi | September 2017 | Avastin (bevacizumab) | Various cancers | Amgen |
| Ogivri | December 2017 | Herceptin (trastuzumab) | Breast and stomach cancers | Biocon |
| Ixifi | December 2017 | Remicade (infliximab) | Multiple inflammatory conditions | Pfizer |
| Retacrit | May 2018 | Epogen (epoetin alfa) | Anemia | Pfizer |
Creating a biosimilar is like reverse-engineering a masterpiece—but without being able to examine the original brushstrokes. Developers must analyze the reference product and create their own manufacturing process to produce a highly similar molecule.
Genetically modified organisms (bacteria, yeast, or animal cells) that produce the desired protein; each manufacturer develops its own proprietary cell line
Controlled environments for growing host cells and facilitating the production of the target protein through fermentation
State-of-the-art equipment to characterize the biosimilar's physical, chemical, and biological properties and compare them to the reference product
Used to separate and purify the target protein from other cellular components after production
The development process begins with analyzing the reference product's structure—its amino acid sequence, protein folding, and glycosylation patterns. Then, scientists work to create a matching molecule, knowing that minor variations are inevitable but must not affect clinical performance 3 .
This requires a comparability assessment rather than establishing efficacy and safety from scratch as with new drugs. The goal is to validate similarity between the biosimilar and reference product through rigorous side-by-side testing 3 .
As biosimilars have entered clinical practice, real-world evidence has accumulated to support their use. A recent systematic review examining rheumatoid arthritis treatment found that biosimilars demonstrate comparable effectiveness to originator biologics, with similar treatment retention rates and disease activity control 4 7 .
The review, which analyzed data from 34,280 patients across 13 studies, found no significant differences in effectiveness outcomes between biosimilars and their reference products 7 .
This real-world evidence is particularly valuable because it reflects experience in diverse patient populations treated in routine clinical settings—beyond the carefully controlled conditions of clinical trials.
The impact of biosimilars extends far beyond the laboratory or regulatory agencies. These products play a crucial role in:
To biological therapies that might otherwise be cost-prohibitive 3
Through price competition—biosimilars are typically priced 50% lower than their reference biologics on average 2
By making expensive treatments more affordable for healthcare systems 3
Competition from biosimilars has already reduced the average sales price of corresponding reference biologics by approximately 25% 2 , demonstrating their potential to generate significant healthcare savings.
The biosimilars landscape continues to evolve rapidly. As of May 2024, the FDA had approved 53 biosimilars 2 , with that number growing to 75 by April 2025 . The future will likely see:
Products that can be substituted at the pharmacy level without prescriber intervention
Extension of biosimilars into new therapeutic areas beyond current applications
Of biosimilar guidelines to accelerate development and approval 8
As the market matures and confidence grows, biosimilars are poised to fulfill their potential as key players in making biological therapies more accessible and affordable worldwide.
The story of biosimilars is still being written, but one thing is clear: they represent a remarkable convergence of scientific innovation, regulatory foresight, and practical solution to one of healthcare's most pressing problems—how to deliver cutting-edge treatments to patients who need them, regardless of cost barriers.