Biosimilars v Biologics

Background

Biologics, also known as biopharmaceuticals, are medications that are extracted from any natural and living source such as plants, animals, or even microorganisms. They are commonly considered to be large complex mixtures, in comparison to small molecule (chemically manufactured) drugs. Not only are the biologics complex, but making them requires scientists to follow a rigid series of steps–much more extensive than that for small molecule drugs. The powerful drug is normally used by scientists to derive the cure of cancer and minimize any damage to joints or organs caused by inflammatory diseases. The reason biologics are so potent is due to their genetic makeup. 

Formation of Biologics:

Biologics are the proteins extracted from living cells. These cells are placed in surveillance laboratories when they are put into shake flasks (a common lab tool used specifically for bioprocess development) filled with nutrients. There, the cells will begin to multiply and build a healthy population. Once the population is big enough, the culture (another name for a group of cells) will be moved to a bioreactor (a device where chemical processes involving cells are carried out). The cells are put through multiple bioreactors that provide optimal conditions for the cells, such as high nutrient soil, levelled temperature and oxygen level to ensure the cells and the protein within reach maximum growth. Once the culture has reached its peak, the cells are cleaned and the protein is removed through the process of filtration, purification and formulation.  This step is lengthy as there are many different techniques used for purification (such as resin and liquid buffers or column chromatography), but nonetheless  vital to the process as it ensures that potential viruses are removed and the protein is converted into a pure and stable form that can be used as medicine. Afterwards, the protein must be concentrated through the Tangential Flow Filtration, a process that filters biomolecules by passing the biologics through semi-penetrable membranes. Finally, the drugs get packed and are shipped to the United States Food and Drug Administration (FDA). The FDA is more particular about biologics than most other drugs because of their complex process and high potential of variability. To ensure a safe, pure, and potent product, the biologics are re-tested in labs and on subjects. Once the drugs get approved, they are packaged and sent to be administered to patients as needed. 

Formation of Biosimilars: 

A similar medication, both in name and purpose, Biosimilars are replicas of biologics that are equally scrutinized by the FDA  and made in 3 major steps. The first step is characterization and perfecting the dose. To make a product so similar to an already FDA produced biologic, scientists have to do extensive research on the biologic cell and use state-of the art technology to replicate the molecular structure of the initial (reference) biologic. This is important to achieve a product that will have most of the same characteristics as the reference. Any differences between the reference and biosimilar have to meet certain criterias from the FDA to ensure that the miniscule differences won’t affect patients negatively. Next, the biosimilars go through rigorous testing to see if they are up to par with the reference biologics. Here, scientists also focus on making the biosimilars interchangeable, meaning that if a clinician switches between the reference biologic and the biosimilar, the patient wouldn’t be negatively affected. This step also includes ensuring that the biosimilar has no clinically meaningful differences from the body’s response with the biologic. Finally, the biosimilar has to be approved by the FDA, where it’s put under the same safety, purity and potency test as the biologic. 

Biosimilars vs. Biologics: 

A big question that arises is why would anyone even create biosimilars? Aren’t there already biologics for treating patients? Biosimilars were made keeping two factors in mind: regulatory checks and cost. 

Factor 1. Regulatory Checks: 

The FDA rigorously checks both biosimilars and biologics, making sure that both are safe and potent. Although the goal is the same, the approach is quite different. For biologics, the FDA requires proof of safety and effectiveness while biosimilars are judged based on their ability to match equivalence between itself and its references. This is because having clinical equivalence between the biosimilar and its reference, must, theoretically, mean that the biosimilar is just as safe and effective. Due to its simpler approval process, biosimilars are often preferred over biologics. 

Factor 2. Cost: 

An important variable in deciding between biosimilars and biologics is the cost. Biosimilars are much less expensive than biologics, as seen through a drop of about $12.6 billion in the production cost over the lost decade. The reason being, biosimilars do not have to go through an extensive period of a development process, and can simply be made by copying the information from research done when producing the reference biologic. With a whopping 25% lower production cost, biosimilars are also more affordable for customers. Because of the lower cost, biosimilars can potentially be covered by more insurance companies which would make treatments more accessible to all people. 

Biologics are currently many scientists’ best bet to cure cancer. However, it does come with its flaws from having a meticulous production process, to taking a long time getting approved by the FDA and affordability. As a result, biosimilars were created, keeping all of the above reasons in mind while bringing a product into the market with the same quality. Now, we can only wait to see if biosimilars will fully replace biologics or not.

References

“Biologics.” Harvard Stem Cell Institute (HSCI), www.hsci.harvard.edu/translation/what-are-drugs-3-biologics. Accessed 28 Feb. 2025.

Biologics Manufacturing Processing Steps, www.gmpkit.com/blog/biologics-manufacturing-processing-steps. Accessed 28 Feb. 2025. 

Genentech. “Building Biologics.” Genentech: Breakthrough Science. One Moment, One Day, One Person at a Time., www.gene.com/stories/building-biologics. Accessed 28 Feb. 2025. 

“How a Biosimilar Is Developed.” Biosimilars Council, biosimilarscouncil.org/resource/how-a-biosimilar-is-developed/. Accessed 28 Feb. 2025. 

Thursday, and Originally published. “Biologics vs. Biosimilars: Understanding the Difference.” Pfizer, www.pfizer.com/news/articles/biologics_vs_biosimilars_understanding_the_differences#:~:text=1%20As%20a%20result%2C%20biologics,to%20access%20for%20some%20patients.&text=Biosimilars%20were%20created%20to%20help,thus%20help%20improve%20patient%20outcomes. Accessed 28 Feb. 2025. 

Ucl. “Differences between Biologics and Small Molecules.” UCL Therapeutic Innovation Networks, 14 Aug. 2020, www.ucl.ac.uk/therapeutic-innovation-networks/differences-between-biologics-and-small-molecules#:~:text=Other%20than%20the%20obvious%20difference,compounds%20manufactured%20through%20chemical%20synthesis. 

“Understanding Biologic and Biosimilar Drugs.” American Cancer Society Cancer Action Network, 12 Feb. 2025, www.fightcancer.org/policy-resources/understanding-biologic-and-biosimilar-drugs.