Biologics vs. Biosimilars: What is the difference?

Biologics are complex drugs that are successfully used in fields such as pharmacology or in the treatment against immune disorders. Biosimilars represent an alternative to reference biologics that can often be produced less costly and open a pathway to broader patient access and market competition. However, the development of biosimilars bears more challenges for manufacturers than, for instance, less complex generic drugs.

In this article, we will define what characterizes biologics and biosimilars, if and where they differ from each other in terms of safety, costs, manufacturing, and approval processes. Further, we propose strategic solutions for manufacturers that help to streamline productions and reduce the risk for contamination and product loss while increasing efficiency.¹ 

Definition of biologics

Biologics are produced by living organisms: Unlike traditional chemical drugs, which are typically synthesized through chemical reactions, the components of biologics are manufactured through biological processes, such as fermentation or cell culture techniques.

They are used in the treatment against various conditions and diseases, such as autoimmune diseases like psoriasis or rheumatoid arthritis, different cancer varieties or genetic disorders (e.g. diabetes) by targeting specific molecules within the patient’s body. Biological medicines come in many forms: Examples of biologic drugs are monoclonal antibodies, stem cell therapies, certain vaccines, recombinant proteins, or transplant tissue.

Biologics consist of large molecules and are often more complex mixtures than synthetic drugs, whose structures and behavior are already known, which makes their characterization and identification more difficult in comparison. ^2 3 4 

Definition of biosimilars

The name biosimilars already hints at their definition: Biosimilar medicines are highly similar to already existent biological products. This is not only in regard to their structure, but also their efficacy, immunogenicity, and patient safety. They are used as vaccines, in the form of monoclonal antibodies, as treatment for immune diseases or cancer, to name just a few.

The original biologic or reference product is already approved by national healthcare institutions like the U.S. food and drug administration (FDA) for instance, while in Europe approval is granted by the European Medicines Agency (EMA).

Frequently, biosimilar products are confused with generic drugs, which are typically lower cost versions of brand-name drugs with the same active ingredient. The most important difference between the two is that, while generic versions are mostly small molecule drugs, synthesized from chemicals, biosimilars consist of more complex molecules and derive from live biological systems. Like their reference biologics, biosimilar drugs may come with a higher risk of variability between batches during manufacturing than generics.^5 6 

Differences between biologics and biosimilars explained

Even though the main focus between biologics and biosimilars lies on their structural similarity, there are some distinct differences concerning topics like safety and efficacy evaluation, production cost, manufacturing process, and regulations.

Production cost

Production costs can vary significantly depending on the specific drug. However, in some cases it can be said that biosimilars are less expensive to produce than their reference biologic. As manufacturers are able to rely on FDA findings concerning the effectiveness and safety of the reference product, this can save costs during manufacturing and improve patient access (Many biosimilars are covered by healthcare providers in the U.S., while more expensive treatment options like biologic therapies are not.). This said, the production of biosimilars after FDA approval is equivalent to biologics manufacturing. ⁸ 

Manufacturing process of biologics and biosimilars

As the structure and mixture of biologic medications has a higher degree of complexity than those of small molecule drugs, they are more difficult to characterize and produce. 
Biologics are cultured in organisms like living cells or bacteria, which are very sensitive to changes in the manufacturing process and prone to contamination through microorganisms if not handled with care. After the cells have grown and reproduced the desired proteins, they can be harvested and purified.

Efficient manufacturing of biosimilars starts with the characterization of the reference biologic. Once the structure has been established, the next step is cell line development. The main goal is always the establishment of similarity to the reference product. A number of clinical trials and tests makes sure that there are no undesired effects that are different from the reference product. ⁹ 

Regulations and approval process

To prevent any undesired side effects and guarantee safety for patients, the development, manufacturing, processing, and packaging of biologics is highly regulated and has to follow specific guidelines set by public health institutions. Among those are cleanroom requirements as well as a number of clinical trials that these prescription drugs have to go through before they can gain FDA-approval on the U.S. market.

The level of regulations is just as high for biosimilars. However, the approval process is more geared towards proving the interchangeability between biosimilar and reference product, while the process for biologics concentrates more on proving that it is compliant in terms of safety and efficacy.

In clinical studies, FDA-approved biosimilars must show the same level of safety and efficacy as the reference product. In the case of interchangeable biosimilars (biosimilars that can be substituted by pharmacists or other healthcare professionals without further consultation with the prescriber), additional requirements have to be met to ensure their safety and efficacy.¹⁰ 

Strategic solutions for manufacturers of biosimilars and biologics

The laborious manufacturing process of biologics and biosimilars profits from strategic solutions that minimize risk factors like contamination or product loss through human errors. Successful, cost and time-effective fluid and cold chain management is essential.

With fully automated solutions by Single Use Support, the manufacturing process of both biologics and biosimilars can be streamlined, while making it easier for manufacturers to meet regulatory requirements at the same time. By adopting complete end-to-end processes, which can be customized to meet the needs of the specific production, current Good Manufacturing Processes (cGMP) can be met more easily while ensuring high throughput, accuracy, and consistency.

Another important argument for automated processes combined with single-use products is the reliable reproducibility of high-standard products. Single Use Support’s automated filling system RoSS.FILL is highly scalable and can be used for different production sizes from development to bulk scale. It is tailored both as a fluid management solution in biosimilar production and in the manufacturing process of biologics.

Alongside the plate freezing platform RoSS.pFTU and the cryogenic freezer RoSS.LN2F as well as the ultra-cold storage freezer RoSS.FRDG and protective packaging, freezing biologics and further cold chain management can be performed with similar ease and in controlled manner. This can make the production of both biologics and biosimilars safer, more efficient and reliable.