Interchangeability and Manufacturing
After defining biosimilarity, EMA poses the next logical question—Will my similar biological medicinal product be considered interchangeable with the reference medicinal product?—then refers readers to the end of the document for the answer: It’s up to national drug regulators.
When it comes to interchangeability, EMA should make its own decisions. Leaving it up to individual countries creates a serious burden for biosimilar developers, who are forced to pursue two tracks of reviews for approvals: EMA’s Committee for Human Medicinal Products (CHMP) and its centralized procedure for authorizing biosimilar products and allowing direct access to the single EU market; and the regulators of each country where they wish to sell their treatments, who must decide on interchangeability.
Fortunately the system requires European rather than individual national authorization for several production processes governing biosimilars. Under EMA’s guidelines, biosimilars are subject to the same level of GMP supervision and GMP standards as any other medicinal product. That includes inspections verifying manufacturing and control activities related to applications.
A second inspection is required for plants outside the European Economic Area (EEA)—which comprises the 27 EU nations plus Iceland, Liechtenstein, and Norway—where no mutual recognition agreement with the EU is in effect and where a plant has not been inspected for GMP compliance in the last three years by “an EEA-competent authority.”
That rule will likely hinder new biosimilar activity in nations outside the EEA: Albania, Belorussia, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldavia, Montenegro, Serbia, and Ukraine. While these nations may lack the EU’s volume of drug activity, they are hardly out of the business. Generic drugmaker Actavis, set to be acquired by Watson Pharmaceuticals for €4.25 billion (around $5.6 billion), is Serbia’s third-largest manufacturer thanks to a production plant there. In January, Actavis won an exclusive license to commercialize recombinant human insulin developed and manufactured by Polish firm Bioton in the EU and several outside-EEA countries.