A biosimilar is a biotechnologically produced medicine that is highly similar to an already approved biological reference product. It is developed and marketed only after the patent protection of the original product has expired. Due to the complex manufacturing process in living cells, an identical copy is not possible.
Biologics are produced in cell cultures or microorganisms, which can naturally lead to slight variations. Biosimilars also show these minimal differences. What matters is that there are no clinically meaningful differences in terms of effectiveness, safety, and quality.
Before approval, the European Medicines Agency (EMA) requires extensive comparative studies. These studies assess whether the biosimilar matches the reference product in efficacy and tolerability.
Biosimilars are mainly used for severe and chronic diseases such as cancer, autoimmune disorders, or inflammatory bowel diseases. Lower development costs often result in more affordable treatment options and broader access to modern biologic therapies.
What should be considered about Biosimilars?
Biosimilars are produced in living cells, which means their properties are strongly influenced by the manufacturing process. Even small changes in cell lines, temperature, nutrients, or production conditions can affect the structure and biological activity of the active substance. Compared with conventional chemical medicines, production is significantly more complex and requires specialized biotechnological expertise.
Despite natural variability, strict regulatory requirements apply. Before approval, manufacturers must prove that there are no clinically meaningful differences compared with the reference product in terms of efficacy, safety, and tolerability. Extensive analytical testing and clinical studies are required for this process.
One major advantage of biosimilars is lower treatment costs. After patent expiration, biosimilars often provide more affordable therapy options and improve access to modern biologic treatments. Actual pricing, however, depends on the healthcare system and reimbursement structure.
Biosimilars vs. Generics: The key differences
Biosimilars and generics are both follow-on versions of approved medicines, but they differ significantly in manufacturing and approval requirements.
Generics are based on chemically defined active substances with an identical structure to the original medicine. Approval usually requires proof of bioequivalence and pharmaceutical equivalence.
Biosimilars, on the other hand, are based on biotechnologically produced biologics. These are created in living cells and have a much more complex structure. Because of the manufacturing process, biosimilars can only be highly similar to the reference product, never fully identical.
| Feature | Generics | Biosimilars |
| Basis | Chemically produced medicines | Biotechnologically produced biologics |
| Active substance | Identical to the original | Highly similar to the reference product |
| Manufacturing | Chemical synthesis | Production in living cells |
| Molecular structure | Simple and clearly defined | Large and complex |
| Approval requirements | Proof of bioequivalence | Additional clinical studies required |
| Variability | Practically no differences | Minor natural variations possible |
| Approval authority in the EU | Decentralized, mutual recognition, or centralized procedures possible | Mandatory centralized approval through the EMA |
Approved Biosimilars in Germany
Many biosimilars are now approved in Germany for different therapeutic areas. They are especially common in immunotherapy, oncology, and chronic inflammatory diseases. The first biosimilar was approved in the EU in 2006 as a follow-on version of the growth hormone somatropin.
Important areas with available biosimilars include:
- Growth hormones
- Insulins
- Blood clotting factors
- Enzymes
- Growth factors for blood cell production
- Immunomodulating agents
Biosimilars are particularly widespread in complex proteins and antibody therapies. Commonly used active substances include:
- Epoetin (erythropoietin) for the treatment of anemia in chronic kidney disease or during cancer therapy
- Adalimumab (monoclonal antibody) for chronic inflammatory diseases such as rheumatoid arthritis or Crohn’s disease
- Trastuzumab for certain types of breast and stomach cancer
- Bevacizumab for various oncological diseases
The number of approved biosimilars continues to grow as patents for more biologic reference products expire.
Manufacturing of Biosimilars
The manufacturing of biosimilars is one of the most demanding processes in modern pharmaceutical development. Unlike conventional medicines, biosimilars are produced in living cells. This naturally leads to minimal variations, which can also occur between batches of the original biologic products.
Development begins with a detailed analysis of the reference product. Important characteristics such as amino acid sequence, protein folding, biological activity, glycosylation, and charge distribution are examined. These properties influence the medicine’s effectiveness, stability, and immunogenicity.
For production, the genetic information of the desired protein is introduced into living cells using biotechnological methods. This is followed by an extensive selection process to identify cell lines that produce a protein as similar as possible to the reference product.
The actual production process includes steps such as:
- Cell expansion in bioreactors (upstream processing)
- Extraction, purification, and refinement of the protein (downstream processing)
- Analysis of structure, biological activity, and consistency of the active substance
Numerous analytical methods are used to characterize a biosimilar. Many product properties are compared with the reference product to ensure a high degree of similarity.
After development, preclinical and clinical studies are conducted to demonstrate that the biosimilar is comparable to the original product in quality, efficacy, and safety.
Typical areas of use (Indications)
Biosimilars are now established in many medical fields across the EU. They are mainly used where biologic reference products have been used for years and patent protection has expired. Common indications include chronic diseases, cancer and autoimmune therapies, as well as supportive treatments in hematology and endocrinology.
A major area of use is oncology and hematology, for example in blood disorders or cancer treatment. Biosimilars are also important in immunology and rheumatology, where inflammatory and autoimmune diseases are treated. In addition, biosimilars are established in diabetes care, ophthalmology, and osteoporosis treatment.
Typical Active Substances and Indications
|
Active Substance |
Reference Product |
Main Indications |
|
Adalimumab |
Humira |
Rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, uveitis |
|
Infliximab |
Remicade |
Chronic inflammatory bowel diseases, psoriasis, rheumatic diseases |
|
Trastuzumab |
Herceptin |
Breast cancer, stomach cancer |
|
Bevacizumab |
Avastin |
Various solid tumors (e.g. colorectal, lung, kidney cancer) |
|
Rituximab |
MabThera |
Lymphomas, CLL, autoimmune diseases |
|
Epoetin (erythropoietin) |
Erypo |
Anemia in kidney disease or during cancer therapy |
|
Filgrastim / Pegfilgrastim |
Neupogen / Neulasta |
Stimulation of white blood cell production, e.g. after chemotherapy |
|
Insulin (glargine, lispro, aspart) |
Lantus / Humalog / NovoRapid |
Diabetes mellitus |
|
Somatropin |
Growth hormone products |
Growth hormone deficiency |
|
Teriparatide |
Forsteo |
Osteoporosis |
|
Follitropin alfa |
Gonal-f |
Fertility treatment (ovarian stimulation) |