Biologics are medicines made from living cells through highly complex manufacturing processes and must be handled and administered under carefully monitored conditions. Biologics are used to prevent, treat, diagnose or cure a variety of diseases including cancer, chronic kidney disease, autoimmune disorders and infectious diseases.
A biosimilar medicine (also sometimes known as a "follow-on biologic", "subsequent-entry biologic" or "follow-on protein product") is a medicine that is similar to another already-authorized biologic medicine (including vaccines, blood and blood components, allergenics, somatic cells, gene therapies, tissues and recombinant therapeutic proteins).
As the US Food and Drug Administration (FDA) notes: Both biologics and biosimilars are isolated from a variety of natural sources – human, animal or microorganism – and can be composed of sugars, proteins, nucleic acids or complex combinations of these substances, or they may even be living entities, such as cells and tissues.
In the US and EU, the two biggest markets for biosimilars so far, a biosimilar must have no clinically meaningful differences in terms of quality, safety and effectiveness from the biologic that it is mirroring and is already authorized (that already authorized product is known as the reference product in the US).
Likewise, in both markets, companies have to carry out studies showing that the biosimilar is similar to the reference biologic and does not have any meaningful differences from the reference medicine in terms of quality, safety or efficacy.
However, as the European Medicines Agency (EMA) notes, data on a biosimilar's reference biologic and the way it is used and made are already available, meaning the amount of data on safety and efficacy needed to win approval for a biosimilar is usually less than the amount needed to authorize the original biologic.
Why are Biosimilars Different From Generics?
Biosimilars and generics differ not only in size, stability and characterization, but also in how they are made, how they behave over time and their mode of action.
A lot of debate has been brewing about the comparisons between generics (which must be identical to their reference products) and biosimilars (which have a natural degree of variability, like with all different lots of the same biologic), with some media outlets calling biosimilars "copycats", or "knockoffs", though such euphemisms can oversimplify what is actually being developed.
Many in the pharmaceutical and biotech industries often refer to generics as small molecule drugs and to biologics and biosimilars as large molecule drugs – meaning the molecules used as the active substances are either small (which for generics means they are synthesized by chemical reactions between different organic and/or inorganic compounds) or large (meaning they are composed of more than 1,000 amino acids and can be produced via modified cells of microorganisms, such as bacteria, yeast or in mammalian cell lines).
The Generics and Biosimilars Initiative (GaBI) offers a good example of the differences between a generic and biosimilar: An aspirin, which is a small molecule drug, measures just 180 daltons (a dalton is the standard unit used to indicate mass on an atomic or molecular scale) and has 21 atoms. That aspirin has a limited ability to initiate an immune response (how a body recognizes and defends itself against substances that appear foreign and harmful) and remains relatively stable over time. However, a biosimilar, which can be a monoclonal antibody or cell signaling protein, measures 150,000 daltons, contains 20,000 atoms, degrades over time and can generate a significant immune response.
As the Biotechnology Innovation Organization notes, differences between generic and biosimilar manufacturers are extensive. Biologics and biosimilars manufacturers must ensure consistency, quality and purity by ensuring that the manufacturing process remains substantially the same over time, whereas a small molecule manufacturer can change the manufacturing process extensively and analyze the finished product to establish that it is the same as before the manufacturing change.
Because of the complexity of biosimilars and the difficulty of manufacturing them, the cost of any given biosimilar is generally higher than the cost of a generic. And even as more biosimilars come to market and create more competition for costly biologics, the price difference between biosimilars and their reference products (biosimilars in the EU have typically been 15- 30% cheaper) may never be as wide as the price difference between generics and their reference products.
Still, according to IMS, some EU countries are seeing a major impact from the introduction of biosimilars (though those cost savings may not be seen in the US until interchangeable biosimilars hit the market).