Biotechnology-derived products now account for an increasingly significant proportion of the biggest selling drugs on the market. This trend is set to continue with both novel recombinant agents and the follow-on or generic biotech products,Biosimilars.
There has been a major increase in the development of monoclonal antibodies, growth factors, recombinant blood factors and other biotech products since the mid 1990’s. Now we are also seeing important developments in stem cell, gene therapy and other advanced therapies.
Recombinant proteins are usually produced by cell culture and fermentation processes. The technology required to ensure the correct protein sequence plus the secondary, tertiary and quaternary structures of the molecules is highly specialised. The manufacturing process is often highly sensitive to minor changes in e.g. different equipment, pH or temperatures.
Purification needs to be very efficient and the analytical techniques to confirm the structure, purity and impurity profiles are very different to those used for small molecules. This all leads to a very different CMC development for a biotech agent compared to a NCE.
Pharmacological models used for small molecules are often not sensitive to or appropriate for recombinant agents, so specific testing models are required, while animal models of toxicology and pharmacokinetics are often not predictive of human behaviour. In clinical development, special attention needs to be paid to issues such as immunogenicity and unexpected adverse effects.
Unlike generic small molecule products, follow-on biosimilars cannot be copied so simply and registered with only a bioequivalence study. They require a full CMC development complemented with specific, comprehensive nonclinical and clinical studies. The EU has taken a lead in the regulation of Biosimilars (see CHMP/437/04 and other guidelines) but the 2012 legislation in USA (Biologics Price Competition and Innovation Act, section 351(k)) will see the US catch up in the coming years.
Most importantly, we have people that you can count on to provide expert advice and support. Our Principals and Expert Advisory Panel members have worked on some of the most important new biotechnology products and some of the most exciting development candidates.
Our experience with Biosimilars is also second to none covering advisory roles in development and regulatory aspects to Due Diligence of partner candidates.
Kinesys has supported the development and registration of products for rheumatoid arthritis, Crohn’s Disease, leukemia, anaemia, cancer indications, blood factor deficiencies and fertility products. We have project managed the regulatory aspects of major manufacturing changes and advised on the intricate and highly specialised CMC issues of a range of biotech products.
Our experience covers the CMC, nonclinical and clinical areas, as well as a profound knowledge of the regulatory requirements for biotechnology products. We regularly prepare Development-Regulatory Roadmaps for early stage biotech products, including novel antibodies, and antibody-drug conjugates (ADC).
Kinesys has taken a lead in this area, advising and liaising with regulatory authorities on early biosimilars even before the first EU legislation was implemented.
Our Biosimilar product list includes various monoclonal antibodies and recombinant hormones. This includes general development strategies, Scientific Advice at EMA, FDA meetings, and Due Diligence for in-licensing of Biosimilars.