The new guideline replaces the ‘Guidance on similar medicinal products containing recombinant human soluble insulin’ (EMEA/CHMP/BMWP/32775/2005), which came into effect in June 2006. The new guideline lays down the non-clinical and clinical requirements for recombinant insulin-containing biosimilars, including human insulin and insulin analogues (both referred to as insulin).

Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant human insulin and insulin analogues EMEA/CHMP/BMWP/32775/2005_Rev. 1
Date: 26 February 2015
Effective date: 1 September 2015
www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/03/WC500184161.pdf

The non-clinical section addresses the requirements of in vitro pharmacodynamic studies and cases when there is a need for additional in vivo toxicological assessment. The clinical section addresses the requirements for pharmacokinetic, pharmacodynamic and safety studies as well as the risk management plan. Requirements for insulin-clamp studies (used to measure how patients metabolize glucose or how sensitive patients are to insulin) and for long-acting insulin preparations are also included.

The guideline also makes it clear that there is no anticipated need for specific efficacy studies since endpoints used in such studies, usually HbA1c (glycated haemoglobin), are not considered sensitive enough for the purpose of showing biosimilarity of two insulins. Clarity is also provided on extrapolation of indications, e.g. from subcutaneous to intravenous use and to other indications and patient populations licensed for the reference product.

In a change from the previously released draft version, EMA has dropped its requirement for ‘manufacturers who are planning comparative clamp studies to consider reports that individuals of African, South Asian or Hispanic descent have reduced glucose clearance’. This change is reportedly due to a comment from European Biopharmaceutical Enterprises, which pointed out that since each subject is his or her own control, ethnic differences should not matter.

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EU guidelines for biosimilars

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