In September 2017, the US FDA made public a draft industry guideline entitled “Statistical Approaches to Evaluate Analytical Similarity.”[1]  Its aim was to provide advice, to sponsors developing biosimilar agents, on how to demonstrate that the product under investigation is “highly similar” to the referenced biological. After taking into consideration the public comments relating to the document, the FDA withdrew the guideline in June 2018 for further evaluation and development to ensure that the scientific and regulatory issues that had been raised would be appropriately addressed.[2]

It is envisaged that the revised guidance will “promote a more efficient pathway for the development of biosimilar products”. In its statement regarding the review of the guidance, the FDA commented on concerns relating to the number of reference samples and the potential for lot-to-lot differences between reference samples, when trying to demonstrate a highly similar follow-on product.[2]

The concept of the “evolution” of biologics and the impact this may have on efficacy and overall safety issues as the compound undergoes changes with time and, ironically, by improving manufacturing processes has been discussed in a whitepaper entitled “Biosimilar vs Biobetter – a two-horse race?” [3]

This paper also discusses the pros and cons of pursuing the development of biosimilars compared with biobetters in terms of the regulatory pathways, safety and efficacy data requirements and differences in development costs and commercial benefits. It also considers the lessons learned and the difficulties overcome when generics were introduced into the market for small molecules drugs and puts these in context with regard to biologics.

Hopefully, the revision of the FDA guidelines will not only streamline the regulatory process, but will put in place measures that will reduce the safety concerns that were raised relating to the true similarity of follow-on biological products…. and hopefully this will advance the competitive market for these complex yet clinically successful molecules, resulting in more affordable treatments for the patients in need.

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