On January 26, Health Canada issued a notice clarifying how a drug's “dormant” status on the drug product database may affect whether that drug must be used as a Canadian Reference Product (“CRP”) for the purposes of an abbreviated new drug submission (“ANDS”). The notice confirms that a dormant status may constitute evidence that a drug is no longer marketed in Canada. As further described below, the result may be that generic manufacturers wishing to enter the Canadian market may be able to rely on alternate CRPs in their ANDSs, and even bypass the Patented Medicines (Notice of Compliance) Regulations (the “PM(NOC) Regulations”). The notice may also have implications for innovators' data protection, which may be lost if a drug is not marketed in Canada.
Background
The ANDS pathway is used by manufacturers of generic drugs to
obtain marketing approval for their products on the basis of the
generic drug having the same pharmaceutical and, where applicable,
bioavailability characteristics as a CRP. But what is an
appropriate CRP?
By default, a drug that is marketed in Canada under a Notice of
Compliance (“NOC”) must be used as the CRP under
section C.08.001.1(a) of the Food and Drug Regulations
(“FDR”). However, if there is no longer any such drug
marketed in Canada, another drug can be used, provided that (i) it
is acceptable to Health Canada; and (ii) it can be used to
establish bioequivalence with a drug that was previously marketed
in Canada (s. C.08.001.1(b)).
In this context, the notice confirms that a dormant status on the
drug product database may constitute evidence that a drug is no
longer marketed in Canada. Health Canada will assign a drug this
status if a manufacturer submits a notice to the effect that the
drug has not been sold on the Canadian market for twelve
consecutive months.
Bypassing the PM(NOC) Regulations?
Health Canada's notice may also have implications for the application of the PM(NOC) Regulations. These regulations provide for the creation of a list of patents pertaining to a drug and aim to ensure that subsequent entry drugs do not infringe on the listed patents. Under section 5 of these regulations, generic manufacturers must choose one of three options when they file for an NOC on the basis of a comparison with (or reference to) another drug marketed in Canada:
- Obtain the consent of the patent owner to the issuance of the NOC
- Wait until all listed patents have expired; or
- Submit a notice of allegation explaining why the generic does not infringe on the listed patents
However, section 5 applies only where the application for an NOC for the generic is based on another drug that is marketed in Canada. To the extent that a dormant status is evidence that a drug is not marketed in Canada for the purposes of PM(NOC) Regulations, generic manufacturers may be able to bypass the requirements of these regulations, i.e. they would not have to choose among the options listed above.
Data Protection Danger
Similarly, the protections granted to an innovative drug under the data protection regulations may be lost if the drug is no longer marketed in Canada (FDR, s. C.08.004.1(5)). If a drug is considered dormant it may be considered “not marketed”. Data protection applies in addition to any patent protection an innovative drug may have. Where a subsequent entry seeks market approval on the basis of a comparison with an innovative drug, an NOC in respect of the generic cannot be issued until eight years after the marketing approval of the innovative drug. Absent data protection, a “dormant” status may result in generics being able to enter the market if there are no longer any patents in force.
Danger for Generic Manufacturers
The notice also alerts generic manufacturers to the fact that a
drug may be listed as dormant even though sales have re-started for
a period of up to six weeks. This situation arises because
manufacturers must notify Health Canada at the latest thirty days
of re-starting sales of the product and, once Health Canada has
been notified, a further two weeks may be needed to update the
database. As a result, there is a risk for generic manufacturers of
submitting an ANDS on a given date under the assumption that their
CRP is acceptable based on section s. C.08.001.1(b), only to
receive a negative decision that a CRP under section s.
C.08.001.1(a) was available and should have been used.
Health Canada acknowledges that the approach outlined in the notice
is “unlikely to resolve all challenges associated with
generic drug development”. Nonetheless, it does clarify that
the date of filing of the ANDS is the relevant date for assessing
eligibility of the CRP, and that any changes to the CRP's
status that occur after that date will not be considered.
Don't Be Caught Dormant
In order to avoid having a dormant status assigned to their drugs, innovators must maintain a minimal level of sales in Canada. Failing this, generic manufacturers may be able to rely on foreign reference products and bypass the PM(NOC) Regulations to gain access to the Canadian market.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.