What are biological products?
Biological medicines first came into use in 1980s. It is a medicine whose active drug substance is natural and not synthetic. It is an entity of a living organism. Biologicals are derived from a living organisms by using recombinant DNA in a laboratory.
The biopharmaceutical product may be derived from organisms like bacteria, yeast, or mammalian cells. Since it is a product of a living organism, the molecular characteristics are much more complex than traditional chemical drugs. Examples of biologicals are infliximab, adalimumab and etanercept.
The structural variability in a biological can be very subtle and it is difficult to fully characterise the end product using available analytical techniques.
Difference between a chemical drug and a biopharmaceutical / biologic
When the cell is synthesized, modifications taking place in the cell can affect biological activity and cause differences in the final drug that is manufactured. Several other factors affect the final product like — the growth conditions, the purification process, the actual formulation and the conditions during storage and transport.
What this would mean is that all these factors put together, the final product may have more than one million product-related variants.
Secondly, biopharmaceuticals are potentially immunogenic which means that they produce a response from the immune system. Small differences significantly affect the immunogenic potential of the drug product. In additional, product- or process-related impurities can provoke an immune response.
The main differences between low molecular weight (chemical) drugs and biological drugs are summarised in Table 1.
Table 1: Overview of the main differences between chemical and biological drugs
| Chemical | Biological |
|---|---|
| Produced by chemical synthesis | Produced by living cell cultures |
| Low molecular weight | High molecular weight |
| Well-defined structure | Complex, heterogeneous structure |
| Mostly process-independent | Strongly process-Dependent |
| Completely characterised | Impossible to fully characterise the molecular composition and heterogeneity |
| Stable | Unstable, sensitive to external conditons |
| Mostly non-immunogenic | Immunogenic |
What are biosimilar products?
A biosimilar medicine is a biological medicine that is developed to be highly similar to an
existing biological medicine (the ‘reference product’).
When the patent for the biological expires, ‘copying’ and marketing these drugs is allowed.
It is like a generic drug of a biological. This product is called biosimilar and costs less.
Copying or reproducing a biological is tough since they are made from living cells. Since
no two cells are similar, exact copies cannot be produced. So, while biosimilar products
are similar to the original product, they are not exactly the same.
Biosimilar medicines offer more cost-effective alternative options and thereby
enhance competition in the marketplace.
A biosimilar medicine is a biological medicine that is developed to be highly similar to an
existing biological medicine (the ‘reference product’)
What does it mean to have no clinically
meaningful difference
For the approval of a biosimilar that is equivalent to the reference product of which it is a copy, it must be proved that there are ‘no clinically meaningful differences’ from the reference product. In other words it is clinically similar in terms of safety, purity, and potency (safety and effectiveness). These are assessed through clinical studies which are called pharmacokinetic (exposure) and pharmacodynamic (response) studies. There may be additional studies as well to establish the similarity.2