The ever increasing complexity of regulations and drug approval pathways has converted regulatory intelligence into one of the key assets during any kind of drug development.

This situation is even more pronounced in the case of biosimilar drug development, where regulations are rather new and lack of (international) consensus exists even regarding critical issues. Delays and drawbacks are inevitable unless the company is truly up to date with national, regional and international regulations and agency opinions. Let’s have a look at common regulatory objectives and hurdles that most companies will face during a biosimilar development programme in Europe.

Early regulatory milestones

Choice of reference (originator/comparator) product as well as foreign comparator product, if applicable

Definition of physicochemical and biological characterisation programme and analytical methods

Preparation of Investigational Medicinal Product Dossier (IMPD) and Investigator’s Brochure (IB)

Definition of non-clinical and clinical development programme; submission of Clinical Trial Applications (CTAs)

Advanced regulatory milestones

Successful conduct of Scientific Advice (SA) with EMA (one or several)

Consensus with EMA regarding the comparability exercise, data to establish biosimilarity

Set up of expert medical and scientific writing team

Definition of calendar and allocation of resources for writing of CTD modules

Final stage regulatory milestones

Pre-Submission Meeting with EMA; agreement on critical issues such as immunogenicity data, extrapolation of safety/efficacy data from different indications, justification of indications, etc. Final draft of Risk Management Plan and Summary of Product Characteristics. eCTD compilation, publishing and Quality Check. Dossier submission via eSubmission gateway (and Common Repository / CESP)

The figure above summarizes some of these points along a hypothetical 6-year timeline.

There are many further steps in addition to the ones listed above, yet importantly they all share common principles. For example, most of the regulatory milestones are both time-critical and successive in character, meaning that failing at any one of them will typically affect overall timelines and negatively influence other parts of the project. Trying to save money via a limited effort while working towards regulatory objectives will eventually cause delays and financial losses. In the worst case, inadequate regulatory effort/knowledge will bring irreparable consequences, such as unfavourable outcome of SA meetings or even (partial) negative opinions for the Marketing Authorisation Application.

Conversely, high quality regulatory work is a fundamental element towards compliance with the overall project goals, calendar and budget.

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