Biosimilars – “the next stage of the biologics revolution” – was the topic of an interesting session at ACR this year.
Many of you will have heard of these the term ‘biosimilar’ (or ‘follow-on biologic’). It is used to describe versions of biologics usually produced after the product comes off patent.
As patents expire, there will be an opportunity to develop biosimilars that may have the same efficacy and safety but could be significantly cheaper than current biologics and provide enormous benefit to those with inflammatory rheumatic diseases in low- and middle-income countries.
But the manufacturing process for biologics is quite different from that of other pharmaceuticals. It’s not just a matter of creating a molecular structure and synthesising that in commercial quantities as with traditional pharmaceuticals .
Manufacture of biologics is dependent on mammalian yeasts or microbial cells which provide the ‘factory’ for production of the biologic in a similar way to brewing beer.
Just as every batch of home brew might be slightly different so are biologics.
This is particularly so when a cell line is changed , a new factory is developed in a different country or the basic materials are sourced from different manufacturers.
The production steps will be similar but not exactly the same and thus the produced biologic will be different . The major concern with a biologic is with its immunogenicity and that is what needs to be evaluated with each new batch or change in manufacturing.
Although changes have been noted in the currently available biologics used so successfully in rheumatology there is no evidence that clinical efficacy of toxicity has been compromised with time. It is important to recognise however, that changes in the molecular and conformational structure will occur with these drugs over time.
Both the FDA and EMA have developed guidelines for evaluation of these products and we will likely see a number of these agents in the next few years. Interestingly in a way biosimilars are being made all the time within the existing manufacturing of the biologic agents and we need to appreciate that.
It will be important to evaluate these agents using switching (where patients are switched between the drugs) trials to assess efficacy and safety using the newly developed guidelines. These biosimilars have great potential and we will all be involved in their development.
References: McKinnon R and Lu CY – Biosimilars are (not ) generics . Editorial – Aust Prescriber 2009 . 32:146-147
Conflict of interest: Peter Brooks has acted on an Advisory Board for 1422 – a Biosimilars research company and has received an honorarium for this activity