EU: new draft guidelines released by EMA

31 January 2011

Tim Harris

On 26 November 2010 the EMA released related draft guidelines, the first on similar biological medicinal products containing monoclonal antibodies (mAbs) and the second on immunogenicity assessment of mAbs intended for in vivo clinical use.

The first set of draft guidelines, for ‘biosimilar’ products containing mAbs, recommend that for non-clinical studies, a risk-based approach should be taken to evaluate mAbs on a case-by-case basis in order to decide on the choice and extent of such studies.  For clinical development, the guidelines noted that a comparative pharmacokinetic study is integral.  It was also noted that although specific CHMP guidance exists on the clinical conditions that are licensed for mAbs, deviations from disease-specific guidelines issued by the CHMP may be warranted (but must be fully scientifically justified).  Extrapolation of clinical efficacy and safety data to other indications of the reference mAb not specifically studied during the clinical development of the biosimilar mAb may also be possible based on the result of the biosimilar exercise evidence and sufficient justification.  Finally, it is stated that post-authorisation follow-up may have to exceed routine pharmacovigilance and may require standardised environments. 

The CHMP’s existing guidelines “Immunogenicity Assessment of Biotechnology Derived Therapeutic proteins” are, in principle, applicable to mAbs.  However, specific aspects of immunogenicity are exclusively or primarily relevant to mAbs and these are addressed in the second set of draft guidelines.  These provide an overview of approaches that may be helpful in predicting and reducing unwanted mAb immunogenicity, the clinical consequences of such immunogenicity and problems experienced with screening and confirmatory assays in its assessment.  The guidelines recommend taking a risk-based approach as a starting point from which immunogenicity testing can be designed.  However, it is emphasised that due to the diversity of risk factors and the variety of mAbs and mAb-related products, the recommendations set out cannot be generalised.  Therefore, an assessment must be based on the identification of risk factors inherent to the particular mAb in question, the final drug product and the patient population to be treated. 

The deadline for comments to be submitted to the EMA on both sets of guidelines is 31 May 2011.