The European Medicines Agency (EMA) released a concept paper on 23 July 2015 with regard to revising the biosimilar guidance document on biosimilar recombinant granulocyte-colony stimulating factor (rhG-CSF).

The current EMA guidance document came into effect in June 2006 and consequently was one of the earliest European product specific guidance for biosimilars. The passage of time plus the experience gained from the evaluation of biosimilars in the intervening years has prompted the revision to the current guidance document.

The current guidance addressed both:

  • Non-glycosylated rhG-CSF manufactured using E.coli (termed filgrastim) and
  • Glycosylated rhG-CSF manufactured CHO cells (termed lenograstim)

The potential changes are three-fold:

  • Whilst the pegylated versions of rhG-CSF are not covered in the current guidance document – their inclusion in the revised guidance is under consideration.
  • Move to a risk-based assessment of non-clinical data with a preference for relying on in vitro studies to demonstrate comparability with the reference product. It is considered that in vitro studies are both more specific and sensitive to detecting any differences between the biosimilar and the reference product
  • Move towards waiving confirmatory clinical trials for rhG-CSF biosimilars. Potentially this requirements could be waived on the basis that the structure, physiochemical characteristics and biological activity of rhG-CSF are measurable with current analytical techniques. Additionally, there are pharmacodynamics parameters of clinical relevance for rhG-CSF. Collectively these factors could lead to the eventual waiving of confirmatory clinical trials for rhG-CSF biosimilars.

This concept paper is open for comment until 31 October 2015 – so it will be interesting to see both the response and the eventual revision to the current guidance.