Health Canada Publishes Draft Biosimilars Approval Guidelines

Health Canada Plots Draft SEBs Guidance

In line with our expectations, Health Canada has published draft guidelines for the approval of biosimilars—which are better known as SEBs in Canada—by the end of the first quarter. Our latest review of Canada's progress in this area (see Canada: 28 December 2007: Health Canada Advances Biosimilars Approval Legislation) indicated that there were only two outstanding issues that the drug approval agency had to address before proceeding with the guidelines. The first concerned the choice of reference biologic—i.e. whether Health Canada should stipulate that only biologics approved in Canada can be used as a reference product by SEBs developers. The second issue was whether SEBs should be considered substitutable with the reference biologic.

The draft guidelines indicate that the agency has reached a decision on both issues, and giving clarification on the grey areas should allow for faster progress with the regulations. Notably, the decision on whether a biotech drug not approved in Canada can be used as a reference product has been made by Health Canada after seeking legal advice. When Health Canada's Mary Alice Hefford spoke at the IBC LifeSciences' Fifth Annual Global Follow-on Biologics Conferencelast December, she said the agency was seeking legal advice because it was concerned that giving approval to a SEB that references a biologic not approved in Canada could mean giving tacit marketing approval to the reference biologic as well. With the benefit of legal advice, Health Canada now states in the draft regulations that the reference biologics a SEB uses in its approval process should be approved in Canada. However, use of a reference product that is not approved in Canada but is marketed in other jurisdictions may be considered at the request of the Minister of Health or on recommendation by the Minister of Health.

With regards to substitutability, the draft guidelines state that "substitutability with the reference biologic product may be granted separate from and/or subsequent to market authorisation of a SEB". The guidelines further state that the substitutability decision will be based on science. The wording of this specific guideline indicates that substitutability is possible, but will not be automatically granted. Furthermore, the determination of substitutability will not be made by the provinces (as has been the case with traditional generics) but by Health Canada, which can best evaluate the science behind substitutability claims.

In addition to these two important clarifications, the following draft guidelines are particularly noteworthy:

• SEBs will be eligible to apply for approval in all indications granted to the reference product, but each indication claimed must be supported with clinical data;
• The pharmaceutical form, strength and route of administration of the SEB must be the same as those of the reference product;
• Until comprehensive SEBs approval guidelines are approved the regulatory approval pathway for new biologic drugs will apply to SEBs;
• The target approval time for a SEB shall be the same as that for an innovative drug;
• Unlike a generic product, each approved SEB must have its own Product Monograph (i.e., labelling requirements) and cannot rely on the Product Monograph of the originator drug; and
• Once approved, a SEB will be considered a stand-alone product. Thus, if there are changes in its manufacturing process the sponsor will only need to compare the pre-change SEB to the post-change SEB, rather than also comparing with the originator biotech product.

Outlook and Implications

These draft Canadian biosimilar approval guidelines are expected to gain final approval after the scheduled consultation meeting in May. The chances of final approval are strong, considering that the recommendations by Health Canada are well thought out, that legal advice has been sought in advance when needed and—perhaps most significantly—that the guidelines are flexible enough to allow for compromise when needed. Global Insight expects to see the final version of the guidelines—along with specific clinical trial guidelines for 2-3 therapeutic areas—to be in place before the end of 2008.

A couple of things in the guidelines that would directly affect both companies developing biosimilars and the producers of originator biotech products are worth noting. First, it is advisable for a SEB sponsor to develop their products choosing a reference biologic that is approved in Canada. However, biotech companies should be aware that keeping an original biologic off the Canadian market would not protect them from SEBs competition. In circumstances where there is a need to approve a SEB whose reference product has not been approved in Canada, the Health Minister can intervene and allow the approval to proceed.