What is a Biosimilar? 

Definitions and Terminology Remain Unclear and Much Abused

Background:  See the Glossary of Biosimilar and Related Terms for a simple glossary of proposed terms and definitions.  But, as discussed below and in other sections, with these products, nothing is simple or clear, including the most basic terminology and definitions. Biopharmaceuticals are the most complex of all commercial products, and discussing biosimilars adds even more nuances and complications.

There are no broadly-recognized or simple definitions for this subset of biopharmaceutical products, the most complex of all commercial products.  'Biosimilar' and related terms can mean very different things to different users and in different contexts.  First, one must understand that these terms involve biopharmaceuticals, i.e., pharmaceuticals manufactured by biotechnology methods, with this involving manufacture by or using living organisms, with biopharmaceuticals involving active bioprocessing and more complex biological molecules/materials.   'Biopharmaceutical' does not include small molecule drugs and natural products, which are drugs (chemical substances) and generally regulated separately from biopharmaceuticals (e.g., in the U.S., as drugs vs. biologics).

Biosimilars (and follow-on biologics, biobetters and other terms) are commonly defined/viewed (and can also be named) on the basis of their:
1) entity ascpects (active agents and formulations), i.e., scientific basis
2) regulatory aspects, i.e., based on approvals, and/or
3) market/commercial aspects, i.e., how products are considered in the real world, especially marketing and popular perceptions.

Defining biosimilars on a regulatory basis is rather simple and clear-cut -- products (or active agents) with current or planned regulatory approvals by an abbreviated 'biosimilar' mechanism.  With biosimilars basically being a regulatory concept, the author recommends definitions (but not nomenclature) be based on this.

Biosimilars' are also often defined based on objective entity/structural similarities among active agents.  In the U.S. at least, biosimilar approval requires an identical primary amino acid sequence with the reference product, but beyond that, many structural modifications can be involved, e.g., glycosylation. Others, including most in the business community and press, often define biosimilars from a market-centric or real-world view, defining "biosimilars" to include any products that (often simplistically) appear (bio)similar based on their use and/or marketing, including products that share some similarities and compete against other.  [If a product looks to be similar to an approved product, e.g., the same product type, e.g., antibody, and will compete for the same indication(s), then it's a biosimilar].  But keep in mind that most everyone, even experts using the strainghtforward regulatory definition, often confound discussions by mixing in terms/concepts, citing products, etc., based on other ways of defining/viewing 'biosimilars.'

There is incredible inconsistency in the application of definitions/criteria for biosimilars.  Actually, the situation is even worse, with most everyone involved usually simply avoiding ever reporting their definition or approach.  And many organizations that would or should otherwise be leaders in this field have taken broader positions restricting their contributing on these issues or imposing major conflicts of interest.  It is difficult to expect clarity and consistency on 'biosimilar' terminology from organizations such as PhRMA, which is now working to rebrand/rename itself, its members and everything 'pharmaceutical' as now being 'biopharmaceutical' (to capitalize on biotech's better public image); and BIO which now often refuses to define biotechnology as involving products manufactured using/by living organisms, reflecting the fact that most of its members are no longer biopharmaceutical or other genuine biotech companies.  Rather, BIO vaguely uses 'biotechnology' to encompass everything life sciences- or biomedical-related (BIO simply can't refuse its mass of members that want to be perceived as or associated with biotechology).  Similarly, most other organizations that should be involved in resolving biosimilar terminology and nomenclature issues are avoiding this (rightly, with it too complex for those not getting seriously involved) and/or have serious conflicts-of-interest.  In the meantime, lack of activity and clarity on these issues favor the status quo (reference products), so established biopharmaceutical manufacturers will likely not get involved until something adverse to their interests comes along.

Besides this author's articles on this subject (see the articles abstracted below), the Biosimilar Medicinal Products Working Party (BMWP) of the EMA, EU, has published an article on the topic of biosimilar terminology, "Biosimilars - Why Terminology Matters," in the August 2011 issue of Nature Biotechnology.  In an associated table, the Working Group proposes a set of terminology and definitions.  As to be expected from an official EU Working Group, the proposed terms are EU-specific, rather vague, use unexplained jargon (e.g, what exactly is a "copy version?") and is severely limited in scope [useless and best ignored; far from "precise terminology" as claimed]. The intent is to provide some type of actual EU definition of 'biosimilar,' something which EU officials had avoided to date (despite granting over a dozen 'biosimilar' approvals).

For further information about terminology and related issues, see the articles discussed/abstracted below or visit www.biopharmacopeia.com.