Short Abstract

The EMA was established in the EU only in 1995 before which all decisions on biologics were made at the national level just as for the FDA.

The recombinant proteins entered the regulatory scene in the USA significantly before Europe, with the introduction of the incentives of the Orphan Drugs Act in 1983. Most of the EU similar biologics (“biosimilars”) approved since only 2006 (EMA) and 2015 (FDA) are those same early products developed as Orphan Drugs.

The EMA and FDA decision making on regulatory requirements have sometime not been aligned over the years, having divergent opinions upon drug substance process changes and consequent drug product changes. Confounding the issue and interpretation of comparability of a biologic during its Life Cycle has been the drug product formulation, dosage form or manufacturing changes.

Therefore, regulatory decisions of approving/authorising of a biologic upon product changes as part of pharmaceutical development pre-and post-first marketing licence are challenging and sometimes controversial.

The presenter will clarify the pharmaceutical development risk factors with a view to the regulators perception or interpretation of possible impact on efficacy and safety. This may mean non-approvability or additional EMA or FDA demands of toxicological or clinical proof. Furthermore, the EU (and worldwide) regulators knowledge of first entry new biologics and biobetters has been heightened because of the introduction of the new biosimilars class of products which presents additional challenges and hurdles to the developers of biologics, which will be clarified.

The presentation will cover the following areas:

• The EMA and FDA decision-making are often not aligned, being divergent upon biologics drug substance process changes, formulation changes and consequent drug product changes.
• The risks and interpretation of comparability of a biologic during its Life Cycle has been assessed in relation to the drug product formulation, in particular, but also dosage form or manufacturing changes. Examples will be provided.
• The new biosimilars class of products presents additional challenges and hurdles to the developers of biologics. Examples will be provided.
• Regulatory decisions before approving of a biologic upon product changes as part of pharmaceutical development pre-and post-first marketing licence are sometimes controversial agency-to-agency and depend on the protein properties, its route of administration and use.