Biopharmaceutical medicinal products (biologics) represent a huge financial market. Thus upon
patent protection expiry of the innovator (reference) biologic there is interest from industry
to gain a portion of this market by launching a 'similar' biologic at a reduced development
cost thus boosting potential gains. The EMA responded to this desire and lead the guidance
process with industry on the topic of biosimilars. Based on the experience gained with
biosimilars in the past the EMA started to introduce a second generation series of guidance
documents which take into account the past current and possibly future challenges of
biosimilars. Those proposals were evaluated by EMA and partially incorporated into new guidance
documents. This work highlights the challenges and risks associated with biosimilar submissions
for large and complex bio-molecules such antibodies. Results: There are unaddressed questions
for the regulator with regard to the unsolved dynamic of heterogeneity and variations of the
quality profile which have potential implications on safety and efficacy. This is neglected
and not taken into account seriously enough by the stakeholders. Solution: Further the only
(in my view) progressive way to deal with such foreseeable situations from the biosimilar
developer's point of view is to incorporate a design space.
