CEPLENE® not an "innovative drug" under the Data Protection Provisions of the Food and Drug Regulations
The Federal Court recently dismissed Epicept Corporation’s (Epicept) application for judicial review of a decision of the Minister of Health (the Minister). The Minister had decided that Epicept’s drug product CEPLENE® (histamine dihydrochloride), which is used for remission maintenance therapy in the treatment of acute myeloid leukemia, was not an “innovative drug” pursuant to subsection C.08.004.1(1) of the Food and Drug Regulations (the Regulations). This meant that the drug was therefore not able to receive the benefit of a period of market exclusivity under the data protection provisions of the Regulations. Epicept’s application sought to reverse the Minister’s decision.
The drug approval process in Canada
It is important to understand several aspects of the way drugs are regulated in Canada. Under s. 2 of the Food and Drugs Act, a “drug” includes any substance or mixture of substances manufactured, sold or represented for use in (a) the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or its symptoms, in human beings or animals, (b) restoring, correcting or modifying organic functions in human beings or animals, or (c) disinfection in premises in which food is manufactured, prepared or kept.
“New drugs” are defined as drugs that contain a substance, combination of substances, or use which has not been sold in Canada for sufficient time and in sufficient quantity to establish in Canada the safety and effectiveness of that substance, combination, proportion, use or condition of use, for use as a drug.
A manufacturer must obtain a notice of compliance (NOC) to market a “new drug” in Canada. To obtain a NOC, a manufacturer must file a new drug submission (NDS) containing sufficient information to enable the Minister to assess the safety and effectiveness of the “new drug”, including substantial evidence from clinical trials.
In addition, to market a “new drug” or a “drug” in Canada, a manufacturer must obtain a drug identification number (DIN), which is an eight digit numerical code that identifies drug product characteristics, including manufacturer, brand name, medicinal ingredient, dosing, pharmaceutical form, and route of administration. DINs are used to track or recall a drug in the event of an adverse drug reaction in a population. To receive a DIN, the manufacturer must file sufficient data to allow the Minister to evaluate the safety and efficacy of the drug for its intended use. A DIN submission does not, however, require substantial evidence of clinical effectiveness, or voluminous clinical trial data.
Therefore, a manufacturer requires both a NOC and a DIN to market a “new drug” in Canada, whereas a manufacturer requires a DIN, but not a NOC, to market a “drug” in Canada.
Histamine dihydrochloride and CEPLENE®
The medicinal ingredient histamine dihydrochloride is an old ingredient and had been previously approved in several “drugs”, all of which were approved using the DIN process. Health Canada, however, deemed that CEPLENE® was a “new drug” because the old medicinal ingredient histamine dihydrochloride was being employed for a new use. Epicept accordingly filed a 124-volume NDS with extensive material and data from comprehensive clinical trials.
Since Epicept held only one patent relating to CEPLENE® (which expires in 2010), Epicept desired a period of market exclusivity by seeking to rely on the data protection provisions of the Regulations upon issuance of a NOC by requesting that CEPLENE® be added to the register of “innovative drugs”.
Whether CEPLENE® is an “innovative drug”
An “innovative drug” is defined in the Regulations as “a drug that contains a medicinal ingredient not previously approved in a drug by the Minister and that is not a variation of a previously approved medicinal ingredient such as a salt, ester, enantiomer, solvate or polymorph.” The data protection provisions provide for a period of eight years of market exclusivity after the first NOC is issued to drugs registered on the “innovative drug” list.
At the heart of this issue was the meaning to be ascribed to the term “drug” as it is referred to the second time in the definition of “innovative drug”. In particular, the issue was whether the second reference to a “drug” was to be read down to be limited to approved “new drugs” or whether it included all approved “drugs”. Epicept took the position that the second reference to “drug” was a reference to “new drug”, while the Minister took the position that the second reference to “drug” was a reference to “any drug”.
The Court agreed with the Minister’s position. Epicept’s position was based on the argument that the data protection regime was to protect the extensive clinical data performed to gain approval for a “new drug”. However, as set out in the relevant NAFTA and TRIPS provisions (from which the data protection provisions were derived), the Regulations were to protect “new chemical entities” – not all “new drugs” are “new chemical entities”. In fact, section 30(3) of the Food and Drugs Act, the Regulatory Impact Assessment Statement to the Regulations, along with the relevant NAFTA and TRIPS provisions, all suggested that one of the intents of the data protection provisions was to “prohibit innovators from obtaining additional terms of data protection for variations of previously approved medicinal ingredients. This exclusion was introduced to avoid the granting of an additional eight years of protection where an innovator seeks approval for a minor change to a drug”. As such, a drug that has been merely approved by the DIN process could not be said to be a “new chemical entity” that has not been approved. The period of exclusivity under the data protection provisions was therefore not available to Epicept for its drug CEPLENE®.