Canada has joined Europe, Japan and several other jurisdictions in providing an administrative pathway for approval of “bio-similar” drugs.  These drugs, known in Canada as "Subsequent Entry Biologics" or "SEB's", consist of biological drugs (proteins, antibodies, and other products derived from biological sources.) which are similar to previously-approved biological drugs.  These are sometimes - inaccurately - referred to as "biogeneric" drugs.  However, unlike a true generic drug, the complex nature of biological products often makes the active component of an SEB different from the original drug.  Until now, approval of SEB's has been largely stalled, pending clarification as to how such products would be reviewed - only a single SEB has been approved. 

The approval of bio-similar drugs has been problematic, due to their hybrid nature which combines features of generic and innovative products.  These products cannot be approved via an Abbreviated New Drug Submission (ANDS) intended for marketing approval of generic drugs.  An ANDS requires only limited testing to establish equivalence with the reference product, while a substantially more complex testing regime is required to establish that a bio-similar drug is equivalent to its reference product in effectiveness and safety.   

The new pathway comes in the form of a "Guidance Document" published on March 5, 2010 by Health Canada.  Health Canada's policy is aligned in essential respects with the centralized procedure in Europe for approval of "biosimilar" products, and are more stringent than for conventional generic drugs.  However, the policy states that the timelines which apply to conventional generic drug approvals will also apply to SEB's, thus indicating an interest in processing such applications on a relatively speedy basis. 

Significant aspects of the new approval process are:

• There must exist a reference product has been both approved in Canada, and also used clinically to a sufficient extent to have accumulated a significant amount of safety and efficacy data.  The reference product must have a similar, but not necessarily identical, composition as the active substance in the SEB.

• The SEB "sponsor" must provide sufficient test data to establish that the SEB is similar to the reference product.  The type of testing depends on the product, and is expected to include a range of tests to establish similarity in a number of respects.  The determination of similarity can involve both non-clinical and clinical testing.

• Clinical trial data (which is additional to the data used to establish similarity) is usually required to establish that the SEB can treat one or more of the disease conditions ("indications") for which the reference product is approved.  In addition, non-clinical data is required in advance of the clinical trials.  The data requirements are more limited than for an original biological drug. 

• Additional clinical trial data is normally required to compare the safety and efficacy of the SEB with the reference product.   Interestingly, if this data shows that the SEB is superior to the reference product, it could be deprived of its status as an SEB, thereby (potentially) subjecting the drug to more comprehensive data requirements (but also removing if from data exclusivity and other limitations).

• A "risk management plan" must be submitted to describe steps that the sponsor will take to monitor the SEB for adverse reactions after approval.  Post-approval reporting of adverse reactions is required, in a fashion similar to non-generic drugs.

The Guidance Document, as well as two companion Guidance Documents, describe the Department's policy that an SEB manufacturer must comply with the procedures that govern generic drugs under the Patented Medicines (Notice of Compliance) Regulations.  These regulations establish a "linkage" system which links generic drug approval to patents owned or licensed by the originator of a drug, and allow the originator to obtain 24 month stay of the approval of the SEB, provided several conditions are met.  The SEB is also subject to any data exclusivity of the originator's drug, which provides up to 8 ½ years of market exclusivity to an original drug.

Since the Guidance document describes the SEB approval requirements in general terms, the Department has scope for interpretation and discretion.  The policy seems to neither "open the floodgates" to bio-similar drugs, nor does it shut the door.  The extent to which such products enter the Canadian market will depend on how the policy is applied and interpreted, as well as the patent-related hurdles that these products will face.  However, in marking a clear pathway for approval of bio-similar drugs, the Department has indicated a general willingness to approve such products.   As patents expire on several popular (and costly) biological drugs, we will doubtless see a number of applications for SEB's being filed in Canada.

The guidance document is available at:

http://www.hc-sc.gc.ca/dhp-mps/brgtherap/applic-demande/guides/seb-pbu/seb-pbu_2010-eng.php.