It Had to Happen Sooner or Later: Health Canada Adopts Draft Guidance for Subsequent Entry aka Follow-On Biologics aka Biogenerics
Ed Silverman over at Pharmalot reported today that Health Canada, the Canadian equivalent of the FDA has beaten the FDA to the punch and issued draft guidance for follow-on biologics known in Canada as subsequent entry biologics. The Canadian regulatory agency recently posted on its website requirements for manufacturers and says it could approve products under existing regulations until laws are amended to include the new approval pathway.
If approved, a subsequent-entry biologic would have to be similar to a previously approved biologic, relying in part on publicly- available safety and efficacy data. Product interchangeability and substitutability would not be automatic, but would be decided on a case-by-case basis, according to the draft guidance. Health Canada says it plans to publish additional guidance documents on specific product classes.
A subsequent-entry biologic would not automatically be approved for all the same indications as the reference product, and data would be required to support each indication in most cases. A meeting to review the draft document is scheduled for May. The proposed Canadian legislation is very similar to that adopted by the European Union for biosimilar products (what they are called in Europe). Not surprisingly the recently proposed US legislation is markedly different than the Canadian and European legislation. Go figure!
One interested aspect, not in any proposed U.S. legislation, is that
the Canadians rule out use of "non-analogous" manufacturing methods.
As I recall, the guidelines require use of analogous expression
systems, cell lines and culture methods, which I interpret as
effectively negating use of many modern bioprocessing technologies and
requiring use of technologies similar to those used the innovator,
which are likely to be 20+ years old. Thus, it appears that a follow-
on erythropoietin (Epogen/Procrit-comparable) product must be
manufactured using a CHO cell line and the same 1970s technology as
used by Amgen, i.e., 1000s of roller bottles in a sprawling plant; and
for many other products, use of large stainless steel fermentation
tanks. Seems like a good way to cripple the competitiveness of
Canadian companies and follow-on products in the world market; and a
blow to companies promoting improved bioprocessing technologies. Many
prominent biogenerics developers are developing products using novel
expression systems (e.g., Streptomyces, in the case of Cangene, a
Canadian company). This may come as a shock to them. Why not let
companies innovate as much as they want in terms of manufacture?