The pharmaceutical regulators define a biosimilar as a biological product that is “highly similar to an existing licensed biologic, allowing for minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product”.

The concept of a biosimilar is not a new one, with such products available for drugs such as insulin or colony stimulating factors having been available for many years. The biologics used in rheumatic diseases differ from existing biosimilars though, being far more intricate entities, comprising large proteins with complex tertiary and quarternary structures that are challenging to duplicate. As such, it is not feasible to produce truly identical products, as subtle changes in structure, such as those that occur in post-translational modification, can never be entirely consistent: hence the use of the term ‘biosimilar’ rather than ‘bioequivalent’ [1]. Even small differences in compound structure can result in variation in clinical efficacy and safety. Therefore the regulatory authorities have imposed stringent requirements on manufacturers developing biosimilar agents to ensure that clinical (but not structural) equivalence is confirmed before marketing authorisation is approved [2]. It is also important to acknowledge that the potential differences in biosimilars to their reference compound will be within the range of variability that is currently observed with batch-to-batch variation of existing products [3].

The European Regulators do not have the authority to enable automatic substitution of biosimilars with reference agents – this is a decision that will need making at a national level [1]. However, such a move would potentially enable pharmacists to switch agents without clinician assent. Such practice raises important concerns. It is known that with existing agents a key challenge is the development of anti-drug antibodies. Such immunogenicity is associated with adverse events and loss of efficacy [4]. In addition it is apparent that an important factor associated with immunogenicity is intermittent dosing regimens [5]. A theoretical concern is that intermittent dosing of an individual with a biosimilar agent and then a reference agent could have a similar effect upon immunogenicity. Therefore, until data are available, switching between products will not be recommended. A practical consideration following from this is that prescription of biologics should move to branded prescribing by clinicians.

However, it is clear that modern manufacturing techniques are superior to those available two decades ago when biologics first emerged in rheumatology and it would be wrong to assume that biosimilars will not perform as well as the reference compounds; evidence to date suggests they are as effective and in the future it is of course possible performance will exceed existing products. Crucially, the arrival of biosimilars will enact a substantial downwards shift in the price of biologics in rheumatology, which funding bodies urgently need.