Generics are defined as drugs that are equivalents of the innovative reference drugs containing the same active pharmaceutical ingredient. The term refers to substitutes for synthetic drugs. Generic drugs are allowed for sale after the expiry of the patent of the original drugs.
Generics, for example acetylsalicylic acid (ASA), also known as Aspirin, are small enough to be synthetical manufactured therefore the medical profile of generics is believed to be equivalent in performance (Figure 1). Due to much smaller expenses in research and development, these drugs only cost a fragment compared to the original1.
A biosimilar is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. The EMA led the way in developing the biosimilarconcept, and the regulatory framework required to ensure high-quality, safe, and effective biosimilar medicines. The terms of the admission of biosimilars have been in place in Europe since 2005 and one year later Omnitrope® was approved by the EMA as the world’s first biosimilar medicine2.
Are biosimilars generics?
The term “generic” is not used in reference to biopharmaceuticals. The European Medicines Agency (EMA) chose the term “biosimilars” to distinguish between both. Structure and production process involving living organisms increase complexity levels; 100 % similarity can never be ensured (Table 1). The production process of biopharmaceuticals varies from one manufacturer to the next and as a consequence every biopharmaceutical has unique properties possibly resulting in severe product quality issues.3 A biosimilar is a drug that is modelled on the original biopharmaceutical (the biological reference product); however, it is not identical to it.
In order to guarantee efficiacy and patient safety, the approval of a biosimilar is much stricter. Its simpler than registration of a biopharmaceutical however much more difficult than generics approval. This is why, despite the huge potential, only 33 biosimilars have been approved by the EMA (as of Dec. 2017)3. Main reason is the complexity of the product; in comparison to synthetic drug it’s size is thousand-fold and requires a host cell as expression system to be manufactured (table:1). However, technical innovations and gain of knowledge are steadily increasing the approval rate, sixteen of the biosimilars were approved in 2017 alone.
Biosimilars – Biologics
U.S. Food and Drug Administration (FDA) use the term follow‐on biologics instead of biosimilars. A biologic is manufactured in a living system such as a microorganism, or plant or animal cells. Most biologics are very large, complex molecules or mixtures of molecules. Many biologics are produced using recombinant DNA technology. Product mimics from vaccines, blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins all are summarized under the term biologicals.
The term “Biobetters” was coined at a conference in Mumbai in 2007 as term for improved biosimilars. Biosimilars, as mentioned above, are generic versions of a recombinant drug that are as exact copies as possible of their role models – for better or for worse! If a direct comparison of the two active substances reveals any specification in which the “copy” of a biologic has other – obviously better – properties than the original, it cannot be approved as a biosimilar. As a biobetter or biosuperior, it must prove its efficacy and safety in a normal approval process.
Modification which come to mind the first are change of the molecular structure of the reference active substance, and change in pharmaceutical form.