What are biosimilars?

Biosimilars are the follow-on products of complex biological medicines and are used to treat serious chronic diseases. They are equivalent to their reference products in terms of efficacy, safety and quality.

Depending on the method of manufacture, a distinction is made between three types of medicinal products:

1. Chemically-synthesized medicinal products, which are produced via chemical synthesis.
2. Herbal medicines, which contain exclusively one or more herbal substances as the active ingredient.
3. Biological medicinal products, whose active ingredients are either isolated from biological materials (e.g. from blood) via a manufacturing process, or obtained via a biotechnological process (cells are stimulated to produce a specific substance).

Examples of biological medicinal products

While the structure of synthetic chemical medicinal products can be clearly described in a chemical formula, biologics are much more complex. Examples of biological medicinal products are insulin, vaccines, antibodies or even growth hormones. To characterise these substances, one always needs several analytical methods, each covering different properties of the products such as purity, structure, polarity or binding intensity.

Originator - Generic - Biosimilar

If a medicinal product with a new substance is approved, it is referred to as an "originator". If a copycat product is approved on the basis of comparability with the originator, it is called a "generic medicinal product" in the case of chemically synthetic substances and a "biosimilar" (medicinal product that is essentially similar to an already approved drug) in the case of biological medicinal product.

Difference from chemically synthetic medicinal product

The difference is that the two chemical-synthetic substances have the same chemical formula, but the two biological active ingredients are not identical but similar ("similar"). This often gives rise to the misconception that biosimilars do not work as well or are less safe than the original products. Among other things, this is a misunderstanding because approval for biosimilars is only granted if there is no significant difference from the originator in terms of quality, efficacy and safety. Thus, not only must analytical comparability to the originator be demonstrated for a biosimilar, but clinical data of direct comparison between the originator and biosimilar must also be provided. Due to minor differences, it must be proven with the help of tests and studies that these have no significant influence on the quality, efficacy and safety.

Only when it has been proven that the biosimilar does not differ in significant aspects from the originator, existing studies and data as well as experience gained can be used, whereby the studies conducted with the originator do not have to be completely repeated.

Accordingly, a tailored program of laboratory studies and clinical trials must also be submitted for each biosimilar to demonstrate through sufficient comparability that the biosimilar product is equally effective and safe to use compared to the originator.

A "biosimilar" is a biological medicinal product that is similar to another biological medicinal product (reference product) already approved in the European Economic Area (EEA). Biological medicinal products (biologics) are products that are produced in a biological system, such as bacteria or yeast, or isolated from a biological source, such as the human or animal organism. The basic principle of a biosimilar development is the comparability between the reference product and the "biosimilar" product, whereby this proof of comparability is conducted in several steps.

1. Step - Comparison of medicinal product quality (comparability of physicochemical properties and biological activity)
2. Step - Comparison of preclinical properties (comparative preclinical studies)
3. Step - Comparison of clinical properties (comparative clinical studies)

The efficacy and safety profiles of a biosimilar product and its reference product should be similar, and generally both products will use them to treat the same diseases. Because the efficacy and safety profiles of the reference product are already established, the expected level of clinical documentation for biosimilar approval is generally lower than for approval of an original biologic. In contrast, the analytical effort with regard to characterisation of the active ingredient is significantly higher compared to the originator.

A biosimilar can only be approved after the data protection period for the original reference product has expired.

Further information on biosimilars

• A list of biosimilars that have been approved by the EMA, as well as further information about these products, can be found on the EMA's "Biosimilar medicines" website
• "Biosimilar medicines overview" of the EMA
• European Commission consensus information document ("What I should know about biosimilars") addresses frequently asked questions (also Q&A for patients and physicians)
• EMA scientific guidelines on biosimilars
• EMA statement on interchangeability of biosimilars