Biosimilars

Products

Biosimilars are copycat preparations of biotechnology-derived drugs (biologics) that have strong similarities to the originator drugs but that are not exactly the same. The similarity relates to biological activity, structure, function, purity and safety, among other things. Biosimilars differ from generics of small molecule drugs in important ways. Biosimilars are usually marketed as injection or infusion preparations. They have only been approved in the EU since 2006 (somatropin), in many countries since 2009 (filgrastim) and in the USA since 2015 (filgrastim). This is because biologics are a relatively young group of drugs. Biosimilars are launched when the patent of the original preparations has expired and they are cheaper than the originals. As a result, they can lead to a reduction in healthcare costs and relieve the financial burden on the healthcare system. In many countries, original preparations may not be exchanged (substituted) for a biosimilar in a pharmacy. A doctor’s prescription for the biosimilar must be available. The so-called automatic substitution, which is common for generics, is therefore not applied. Therefore, when prescribing biologics, the brand name and not the active ingredient name should be indicated on the prescription.

Structure and properties

Biologic drugs, such as proteins, enzymes, receptors, or antibodies, are manufactured with the help of living cells or organisms. Proteins can consist of hundreds of amino acids and have a high molecular mass (5 kDa to 150 kDa). This is in contrast to conventional drugs, whose molecular mass is usually less than 1 kDa (“small molecules“). Due to the complicated and highly sensitive manufacturing process, these are not exact copies of the active ingredients, unlike the small molecule generics. They are similar, but not exactly the same. This is also due to the fact that even the original biologics are subject to variability and small differences exist between different batches. For example, while the amino acid sequence of the biosimilars is identical, they may differ in three-dimensional structure, post-translational modifications (e.g., glycosylation), and immunogenicity. Therefore, compared with generics, the approval process is more extensive, more expensive, and includes clinical trials.

Effects

The effects of biosimilars are essentially the same as those of the originator products.

Indications

Approved biosimilars are used for the treatment of rheumatic diseases, psoriasis, inflammatory bowel disease, cancer, thromboembolic diseases, neutropenia, diabetes mellitus, growth disorders, and anemia, among others. The indications of a biosimilar may include all or only a selection of the indications of the original product. Thus, a biosimilar may not be approved for all indications of the original.

Dosage

Biosimilars are usually administered parenterally, ie, as an injection or infusion, because of insufficient oral bioavailability. Patients must be monitored and accompanied by a physician during the switch because tolerability may differ.

Agents

The following list shows a selection of active ingredients of which biosimilars are available (Switzerland, EU, USA). The original products are listed in parentheses.

Adverse effects

Adverse effects depend on the agents used. Administration of biologics may lead to the development of autoantibodies directed against the therapeutic agents, which cancels the effect. Furthermore, allergic reactions are possible (immunogenicity). Safety must be further monitored after approval (pharmacovigilance program).