Despite the pandemic, last year the US FDA worked through several issues which impact biologics and biosimilars, and I thought that it would be worthwhile looking at some of these.
In fact, last February was a very busy time! The first development was an announcement on Feb 3rd of a collaboration between the FDA and the Federal Trade Commission aimed at “supporting appropriate adoption of biosimilars, discouraging false or misleading statements and deterring anticompetitive behaviors in the biologic marketplace”. A public workshop held in March to discuss this issue can be viewed online (1).
Also in February, the FDA issued its Final Rule regarding the definition of a “biological product” (2). This defines a protein as “any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size.” Importantly it addressed the transition of products previously regarded as small molecules, such as Insulin and Somatropin, to biologics.
Later that same month, it then launched an online, searchable database version of the so called “Purple Book”- a “List of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity and Interchangeability Evaluations” (3). Draft guidance documents were also issued concerning “Promotional Labeling and Advertising Considerations for Prescription Biological Reference and Biosimilar Products” and “Biosimilars and Interchangeable Biosimilars: Licensure For Fewer Than All Conditions of Use for Which the Reference Product Has Been Licensed”.
Arguably, the main developments from the US FDA during 2020 were centered on Interchangeability- a subject unique to the BPCI Act (2009) which outlines a route via section 351(k) of the PHS Act by which a biosimilar may be substituted for a reference biologic without the intervention of a prescriber and involves additional clinical “switching studies”. The FDA published its final guidance document “Considerations in Demonstrating Interchangeability With a Reference Product Guidance for Industry” (4) on May 10th, after spending nearly 2 years reviewing industry comments and revising the draft. It is interesting to note that in the final guidance they have dropped the term “fingerprint-like” similarity.
To date, no interchangeable biosimilars have been approved and only one company has publicly disclosed that it is seeking approval, although now with Insulin products designated as biologicals/ biosimilars this could change in the future. In this final guidance, the FDA concisely outlines the impact structural and functional complexity has on the extent of clinical data required. The Guidance states that “Advances in analytics may allow for extended analytical characterization that affect the extent of other data and information needed……..” Following on from this, a Draft Q&A Guidance for Industry on Biosimilars and Interchangeability was posted in November 2020 (5).
Although 2020 marked the ten-year anniversary of the enactment of BPCIA, a slowdown in biosimilar activity occurred with only 3 new biosimilars:
This is the lowest number since 2016 and significantly fewer than the record breaking 10 in 2019. Presumably, this slowdown can be attributed to the effects of the pandemic which certainly caused delays in inspections with knock-on effects on approval decisions.
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