An introduction to biosimilars

Biosimilars are versions of biological reference drugs and are intended to be on a par with in terms of safety, efficacy, and quality. While biologics have changed many lives for the better and are successfully used in oncology, as vaccines, or in the treatment of different immune diseases, they remain quite costly. This is due to the fact that they are usually patented for several years in order for the extensive research and development efforts to be amortized.

Biosimilars can present a more accessible option once the patent for the reference drug expires, and may broaden patient access to prescription drugs against rheumatoid arthritis, bowel diseases such as Crohn’s disease, psoriasis, and different cancers.

In the following, we will give an introduction to biosimilars, describe the differences between biosimilars and biologics, and provide an overview of FDA approved biosimilars. Further, we will talk about their development and manufacturing processes and how these can be optimized with single-use technologies.

Biosimilars definition

Biosimilars are drugs that resemble to biological products like monoclonal antibodies or gene therapies in terms of quality, efficacy, and safety. Just like biologics, biosimilar products are crafted with the help of living cells or microorganisms, thus may show minimal variety between batches.

Interchangeable biosimilars are a special category of biosimilars, as they come especially close to their reference product. Due to their great resemblance to the original biologic, interchangeable products can be given out by pharmacies instead of the corresponding biologic without further consultation with the prescribing healthcare professional, similar to a generic drug being given out instead of a brand-name drug. To achieve this status, they have to fulfill additional requirements by national health authorities like the U.S. Food and Drug Administration in the approval process.^1 2 3 

Biologics vs. biosimilars: What is the difference?

Even though biosimilars and biologics have a lot in common, they are not the same. This is due to a level of variability that exists between the biosimilar and the reference product.

While chemical drugs can be replications of generic drugs, the manufacturing process of biosimilars is more complex and depends on factors such as the selected cell line, temperature, manufacturing environment and much more.

This is why biosimilar drugs inevitably show some level of variety between batches, even though there are no clinically meaningful differences for patients.

Although biologic drugs have the potential to change the lives of patients suffering from different immune diseases and are an effective treatment option for a lot of cancer varieties, patient access is still limited due to high costs. These result from pharmaceutical research and development, with only a few products ultimately being able to enter the market, which are then patented for several years in order to keep the work on these innovative drug products attractive and to drive scientific progress. Biosimilars are a lower cost alternative to brand name drugs due to cost savings during the development process. ^4 5 6 

History of biosimilars

The concept of biosimilar medicines emerged in the 1980s and gained traction in the following decades, as biologic therapies became increasingly important for the pharma industry. However, the regulatory pathways for approving biosimilar products were not established until the early 2000s. In 2005, the European Medicines Agency (EMA) introduced guidelines for biosimilar approval, leading to the approval of Omnitrope as the first biosimilar in Europe in 2006.

The USA followed suit with the Biologics Price Competition and Innovation Act (BPCIA) in 2010, creating a regulatory pathway for biosimilars. The first biosimilar in the U.S., Zarxio (filgrastim-sndz), was approved in 2015. Since then, biosimilar approvals by the FDA have increased across various therapeutic areas.

Globally, biosimilars have gained acceptance and are now integrated into healthcare systems to enhance patient access and reduce costs. While facing challenges such as regulatory complexity and market acceptance, biosimilars continue to offer opportunities for innovation, competition, and affordability in biologic therapies.^7 8 9 

Overview of FDA approved biosimilars

While the European Union gave way to the first biosimilar drug called Omnitrope in 2006, the first biosimilar approved by the FDA was Zarxio (filgrastim-sndz) in 2015. Since then, 49 biosimilar medicines have been approved to date (April 2024).

Among the latest FDA approvals are biosimilars to the arthritis drug Humira with adalimumab as the active ingredient. The full list of approved biosimilars as of today, with reference biologics, manufacturers and information on formulary changes, can be found on the FDA’s website or in our latest article on FDA-approved biosimilars.¹⁰ 

Manufacturing biosimilars – what to consider

Manufacturing biosimilars is a sensitive process that can easily be impacted by various challenges, such as molecule variability, contamination risks, or product loss through human errors. One important part of the manufacturing process is taking precautionary measures for efficient and safe fluid management, freezing and thawing, as well as ideal transport and storage conditions – necessary to be able to guarantee high quality products. 

Fluid management

Effective fluid management during cell culture, purification, formulation and filling and dispensing mechanisms is of the essence to guarantee a successful product. By using state-of-the-art fluid management systems, contamination risks can be minimized through a reduction of exposure times. Fully automated closed systems are the solutions for handling sensitive protein formulations in a way that is compliant with current good manufacturing practices (cGMPs).

To allow for more flexibility, it is important that fluid management is scalable, to move quickly from development phase to manufacturing. Regular controls are necessary to minimize microbial contamination or cross-contamination risks between batches and help manufacturers intervene if necessary. 

Transport and storage

To prevent damage during transport and storage of biologics and biosimilars, containers need to be protected and stored safely to prevent alterations and product loss. Stable temperature and precise monitoring are additional prerequisites for storage freezers used in biomanufacturing. 

Ideally, products can be transferred easily and in short time from freezers to storage, to prevent temperature changes that could affect the product’s efficacy and safety. Additionally, space is typically limited in storage facilities and during transport. This produces a need for space-saving stackable solutions that can be kept reliably at the required low temperatures. ¹⁴ 

Challenges involved in the manufacturing of biosimilars

As already established, there are numerous challenges in the manufacturing of biosimilars. These range from contamination risks and drug substance exposure to product damage through uneven freezing and thawing rates. Further, product loss, often caused by human errors if manual intervention is necessary, are problems that can occur in the manufacturing process of biosimilars.

The regulatory framework surrounding the manufacturing of biosimilars was designed to ensure their safety and efficacy. Current good manufacturing practices or cGMPs include factory design, documentation, standardized labeling practices, cleanroom requirements, and staff safety precautions when handling drug substances. Compliance is necessary but bears its challenges for manufacturers.

To stay economically competitive in the expanding market of biological and biosimilar drugs, which is predicted to double its revenue until 2034, it is important to streamline processes, save time, and reduce costs. Automated solutions and state-of-the-art technology can support manufacturers in building an efficient manufacturing process.¹⁵ 

Efficient strategies for manufacturing biosimilars

With innovative strategic solutions from Single Use Support, efficiency in the manufacturing process of biosimilars can be optimized. With the help of automated fluid management systems, the need for human intervention and the risk of cross contamination can be reduced. At the same time, production speed is increased.

To reach maximum efficiency, it is possible to seamlessly incorporate different single-use technologies into the production chain. All products are scalable, to allow for more flexibility during the production cycle. Single-use bags are aseptically and precisely filled with RoSS.FILL and protected in RoSS® shells against product damage during storage and transport.

If the single-use bags must be frozen for transport, they can be cooled down efficiently to -80°C with RoSS.pFTU. This freezer uses plate freezing for stable freezing to prevent protein denaturation. Should even lower temperatures be required, the cryogenic freezer RoSS.LN2F is ready to achieve them in a safe and controlled manner.

To maintain stable temperatures during transport and storage, RoSS.FRDG keeps containers reliably at temperatures as low as -75°C, helping them to preserve their effectiveness and safety until they are needed.