Today, we find an increasing number of labels that refer to biopharmaceuticals: biosimilars or followon biologics, biobetters and biosuperiors.  All of these products are supposed to show “similarity” to biopharmaceuticals already on the market. But similarity is rather complex when we talk about biopharmaceuticals. Resolving questions of labeling can provide optimal benefits for decision makers, health authorities, prescribers and patients.

Biosimilars differ from generic drugs by their characteristics, their raw materials and manufacturing processes. Differences between generics and biosimilars focus on product development, marketing authorization, and post-registration monitoring. There are essential differences between the two regulatory pathways relating to biosimilars. Unlike generic medicines, where the active ingredients are identical, biosimilars, by definition, are not likely to be identical to the originator biologic. They are similar, but not the same.

Currently, it is impossible to duplicate an original biopharmaceutical, precisely. Biopharmaceuticals, which utilize the most modern and sophisticated science, are very difficult and costly to produce, and the cost for a biosimilar tends to be 20-100-times higher than for a small molecule pharmaceutical (Fuhr, Blackstone 2010). Biologics made by different manufacturers differ from the original productand from each other. Where the active ingredient is required to be identical, the manufacturing process through which a biologic is made cannot be exactly duplicated by another manufacturer. Follow-on products containing rather (bio)similar active agents are classed as either biosimilar (much the same) or biobetter (too different to be approved as a biosimilar, and believed to offer some advantage).

Biotherapeutics have emerged as targeted drugs for indications such as cancer, autoimmune diseases, and hormone/enzyme disorders. But similarity is an elusive and complicated concept facing comparisons of biological molecules, as even minute changes to a molecule’s structure can dramatically affect its function in the body.

At this point, there is no set regulatory pathway for the subgroup of biosimilars known as “bio-superiors” or “biobetters” or “next generations.” They refer to a biological product category that is similar to an already-approved biological product, but is also superior in one or more product characteristics.

Biobetters allow companies to target an established mechanism, safety and efficacy profile, but generate sales of a new molecular entity. They are also protected by patents. Although development costs for biobetters are similar to those of a new biological product, chances of successful registration are significantly higher. This means lower business risk and potentially higher return on investment.

Then there is another group known as “me-too” biologics, which are not directly compared and analyzed against a licensed reference biological.

All these new labels are creating whole new economic targets and market segments, and are likely to result in a brand new pharmaceutical innovation model, one that involves lower risk, faster time to market and less investment. They are also changing the concept of “new product,” and leading to different questions: To what extent can biosimilars and biosuperiors be considered innovative?  Can this innovation be assessed?

The case of “biobetters” illustrates a product differentiation strategy comparable to what we see with supergenerics and hybrid products, and is likely to bring a new dynamic of competition to the market.  These products can also improve patient access to more affordable innovative products. In turn, the whole concept of a new pharmaceutical product is evolving.

One thing is certain. Prices of biosimilars will not decline by 70% as occasionally occurs in the case of generics, but will probably be 25-30% less than the original. The developing standards will evolve; the licensing requirements and marketing are difficult. Patient adherence, patient compliance and long run market access targets are major challenges to face before any decisions are made.

Some have asked whether this focus on “similar” products is useful. Wouldn’t development of new, orphan drugs be better? Perhaps not. Biosimilars would allow patients who do not respond to one type of prescribed treatment to switch to other similar therapies, an important benefit.

The competition that these similar versions bring into the market creates economic value that goes beyond cost. However, a new economic paradigm is needed to take into account the cost of innovativeness in these various versions of biopharmaceuticals. In examining these labels, perhaps the time has come to look a bit more closely at “differences,” rather than just similarities.

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Fereshteh Barei
Dauphine University, LEGOS laboratory, Paris

Fereshteh Barei is an academic researcher at the LEGOS Lab for Health Economics and Management at the Dauphine University in Paris.  Her research focuses on global healthcare innovation strategy, particularly in the field of generics and super generics.