The EMEA release for review a draft concept paper today (24th March) on immunogenicity assessment of monoclonal antibodies for in-vivo clinical use. the consultation period lasts until June 2009.
Backgound to the concept paper
Unwanted immunogenicity is a significant problem with therapeutic biologicals. The clinical problems associated with unwanted immunogenicity vary in nature and incidence. The importance of the unwanted immunogenicity problem has led to the preparation and adoption of the ‘Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins’ by the CHMP (adopted April 2008).
Monoclonal Antibodies (mAbs) comprise a large important class of therapeutic biologicals. Different mAb products share some properties, but may differ in other aspects. Many mAb products are known to be associated with unwanted immunogenicity. Some issues pertaining to unwanted immunogenicity of mAbs differ in important aspects from those generally associated with therapeutic biologicals.
The Main problem being addressed
The incidence of immunogenicity associated with mAbs differs greatly between products, patients and even in different studies with the same product and patient type. The complexity of structure of mAbs possibly explains at least some of this variation. In some cases, especially with humanised or human sequence mAbs the immune response is predominantly anti-idiotypic, which clearly can compromise clinical responses to the mAb. In some cases the induced antibodies reduce clinical responses to the mAb to such an extent that further therapy has to be terminated.
The very large number of mAbs in clinical development and undergoing regulatory scrutiny emphasises the critical need for provision of appropriate guidance on the unwanted immunogenicity of this large class of biologicals. Questions on immunogenicity are often asked during assessments of marketing authorizations for mAbs. The development of biosimilar mAbs is prevalent in various parts of the world, which again stresses the importance of having good guidance available, as unwanted immunogenicity is well known to also be a concern with biosimilars.
The main recommendation from this concept paper are, the drafting of a guideline on immunogenicity assessments of monoclonal antibodies intended for in vivo clinical use. The EMEA are looking for expert input and opinion into this subject from the pharmaceutical industry.
If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com
Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.
