Canada Gazette

In the November 2001 Doha Declaration, the World Trade Organization (WTO) members recognized the gravity of the public health problems afflicting many developing and least-developed countries, especially those resulting from the human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), tuberculosis, malaria and other epidemics.

On August 30, 2003, negotiations among WTO members resulted in a decision (General Council Decision) waiving certain provisions of the Agreement on Trade-Related Intellectual Property Rights (TRIPS) which essentially prevented nations in need from importing less expensive versions of pharmaceutical products. The General Council Decision facilitates affordable access to medicines to treat HIV/AIDS, malaria, tuberculosis, and other epidemics, in least-developed and developing countries with insufficient or no domestic capacity to manufacture pharmaceutical products. Canada was the first country in the world to declare its intention to implement the General Council Decision domestically.

Bill C-9, An Act to amend the Patent Act and the Food and Drugs Act (The Jean Chrétien Pledge to Africa) [hereafter referred to as "the Act"], which received Royal Assent on May 14, 2004, made amendments to the Food and Drugs Act (FDA) and the Patent Act. The Act amended section 30 and subsection 37(1) of the FDA. Section 37 is amended so that the FDA, Food and Drug Regulations and the Medical Devices Regulations would apply to all products exported under the General Council Decision. Section 30 of the FDA is amended to provide the Governor in Council with the authority to make the regulations required to implement the General Council Decision. The amendments to the Patent Act set out the conditions under which an authorization is given to use the patented inventions required to manufacture the drug or device under Canada's program to implement the General Council Decision.

Health Canada will review a pharmaceutical product based on Canadian standards and requirements. The definition of a pharmaceutical product under the General Council Decision includes products that Health Canada regulates either as drugs or as devices. It is important to note that the Food and Drugs Act and its accompanying regulations apply to pharmaceutical products included under this program. These proposed Regulations are to be read in addition to all the other requirements that have to be met by manufacturers.

The proposed Regulations outline the conditions to be met in order for the Minister of Health to notify the Commissioner of Patents that the pharmaceutical product (drug or device) meets the requirements of the FDA and the applicable regulations. The Act requires that Health Canada notifies the Commissioner of Patents that the product meets the FDA and its regulations before the Commissioner of Patents can issue an authorization (i.e. compulsory licence) to a manufacturer. Furthermore, Canada has certain obligations under the General Council Decision, such as the requirement to distinguish exported products from the domestic version of the product and to identify the product as having been manufactured under this program. This requirement serves as a mechanism to address the risk of diversion and re-importation of products. As a result of Canada's obligations under the General Council Decision, new regulations that include markings which identify the product as having been manufactured in Canada to the extent permitted by the General Council Decision and that distinguish it from the version on the Canadian market are necessary.

This regulatory amendment proposes that Division 7, entitled "Sale of Drugs for the Purposes of Implementing the General Council Decision," be added to the Food and Drug Regulations in order to implement the General Council Decision.

The proposed Division 7 outlines submission requirements, conditions for the Minister of Health to notify the Commissioner of Patents, and pre-export notification requirements.

In addition to the filing of a submission, as is currently required under the FDA and its regulations, there are other submission requirements which a manufacturer must meet.

For example, a statement of intent to apply for an authorization from the Commissioner of Patents must be submitted to Health Canada.

Additionally, a "Distinguishing Features" package must be submitted to Health Canada in accordance with this proposed regulatory amendment. The package must contain all the distinguishing markings, colouring and labels as required in the proposed Regulations.

This proposed regulatory amendment requires that the pharmaceutical product(s) be distinctly different from the version of the product(s) sold in Canada, and be easily identifiable as product(s) included in this program. This is accomplished through markings, colouring and labelling, as required. For solid dosage forms, such as tablets and capsules, the letters "XCL" must be marked on the dosage form and the colour must be significantly different than the version sold in Canada. For non-solid forms, such as suspensions and powders for reconstitution, the letters "XCL" must appear on the immediate container. For all labels, "XCL" must be permanently displayed, followed by the Health Canada issued export tracking number (unique for each authorization). In addition, all labels must display the phrase "FOR EXPORT UNDER THE GENERAL COUNCIL DECISION. NOT FOR SALE IN CANADA" or "POUR EXPORTATION AUX TERMES DE LA DÉCISION DU CONSEIL GÉNÉRAL. VENTE INTERDITE AU CANADA". The manufacturer must provide sample labels to Health Canada.

Following the successful review of both the submission and the additional distinguishing features package, and upon receipt of a copy of the application to the Commissioner of Patents for an authorization, the Minister of Health will notify the Commissioner of Patents that the drug meets the Food and Drugs Act and its regulations. Health Canada will also issue an export tracking number.

Manufacturers must notify the Minister of Health no less than 15 days prior to the start of manufacturing of each lot.

Schedule 1 to the Patent Act, added by the Act, lists the pharmaceutical products included in this program. Although there are currently no devices listed on Schedule 1, it is contemplated that medical devices (e.g. HIV diagnostic test kits) could become eligible for this program following addition to Schedule 1 of the Patent Act. Therefore, amendments to the Medical Devices Regulations are being proposed to allow medical devices to be identified as included in this program. The requirements for unique markings, labelling and notification to the Commissioner of Patents necessitate the addition of new provisions under the Medical Devices Regulations.

Similar to the regulations respecting drugs, medical devices are required to be permanently marked with the "XCL" identifier on all permanent components. Labels are also required to be permanently marked with an "XCL" identifier followed by the control number assigned to Class III and IV devices by the manufacturer, and the phrase "FOR EXPORT UNDER THE GENERAL COUNCIL DECISION. NOT FOR SALE IN CANADA." or "POUR EXPORTATION AUX TERMES DE LA DÉCISION DU CONSEIL GÉNÉRAL. VENTE INTERDITE AU CANADA."

The Minister of Health will notify the Commissioner of Patents that the medical device meets the requirements of the Food and Drugs Act and its regulations if

— The manufacturer and the device meet the Food and Drugs Act and its regulations;

— A copy of the application for an authorization has been provided by the manufacturer to the Minister of Health;

— A sample of the label has been provided by the manufacturer to the Minister of Health; and

— Information relating to the manner in which the mark is to be applied to the permanent components of the device has been provided by the manufacturer to the Minister of Health.

The notification to the Commissioner of Patents will be similar to the form issued for drugs.

The manufacturer is required to notify the Minister of Health no less than 15 days prior to commencing the manufacture of the device.

In addition to the proposed Regulations discussed above, a number of Health Canada policies, guidelines and standing operational procedures (SOP) must be updated or created for pharmaceutical products exported under this program.

The Management of Drug Submissions Guidance will be updated to include submissions under the General Council Decision as a submission type to which the guidance will apply and outline the process for this type of submission.

The Management of Device Licence Applications Guidance will be updated so that the manufacturer control number for all Class III and IV medical devices referred to in paragraph 21(1)(d) of the Medical Devices Regulations is used to track distribution of devices manufactured under the General Council Decision. The document will also outline the process applicable to these products.

Other guidance documents, such as Changes to Market New Drugs, Cost Recovery Guidance Documents, and Guidance for Interpretation of Significant Change of a Medical Device will be updated.

A guidance document for drug colouring will be created to provide guidance on the requirement that a drug's colouring be "significantly different" from the version of the drug sold on the Canadian market.

Other guidance documents on Fixed-Dose Combination Products (FDCs), the processing of adverse event information, and pre-export inspections will also be developed.

These Health Canada policies, guidelines, and SOPs will be revised or developed once this program becomes operational.

Health Canada is proposing to make the least number of amendments to existing regulations as is necessary. Amendments made to the Patent Act and the Food and Drugs Act by virtue of the Act contain requirements for notification to the Commissioner of Patents and for distinguishing features. The details governing them must be made through regulation in order that they will have the force of law. Drugs exported under this program must meet the Canadian standards. Consequently, few changes are required to the Regulations beyond those relating to the added requirement for markings that distinguish the drug from the version on the Canadian market, and Health Canada's notification to the Commissioner of Patents.

The conditions under which Health Canada will notify the Commissioner of Patents is contained in the proposed Regulations. This will ensure that the pharmaceutical product meets Canadian requirements for safety, efficacy and quality including distinguishing features. The distinguishing features requirement exists to ensure that Canada upholds its obligations under the General Council Decision of the WTO to implement anti-diversion measures.

Various alternatives were considered to prevent the diversion of products. For example, it was considered whether the manufacturer could determine what the distinguishing markings would be. This was found to be unacceptable because it would be difficult to track the various marks used by different companies. Another option considered was to use a mark that a generic manufacturer already uses on its Canadian products. This option was rejected because the General Council Decision requires products to be identified as "being produced under the system set out in [the] Decision through specific labelling or marking." Marks that a generic manufacturer already uses on its Canadian products do not identify the product as belonging to this program. It was determined that, with a common and unique mark, diverted products would be immediately identified. Therefore, these common and unique marks needed to be put into regulation.

An additional alternative considered was the use of the World Health Organization (WHO) pre-qualification list instead of a full review of drug submissions filed in Canada in order to expedite the review process and enable developing and least-developed countries to gain access to pharmaceutical products in a timely manner. This alternative was rejected because the Act requires the Minister of Health to notify the Commissioner of Patents that pharmaceutical products meet the requirements of the Food and Drugs Act and its regulations.

The Act puts into place a program that seeks to implement the General Council Decision. The program exemplifies Canada's important role on the international stage in advancing global health and human rights. It also serves to encourage other G8 nations to implement similar programs.

The intention of the General Council Decision is to assist countries in need and protect public health. This program is therefore not aimed at pursuing industrial or commercial objectives.

In light of the humanitarian nature of the program, manufacturers are expected to provide the products at a non-commercial price. Generic manufacturers will be able to sell pharmaceutical products which are under patent protection in Canada to eligible countries. It is not anticipated that the additional requirement for distinguishing features will be significantly costly for manufacturers.

The proposed changes will not affect Canadians' access to drugs or medical devices, nor will they affect the established performance targets for drug assessments, as the Government of Canada has approved funding for Health Canada to implement this program. This funding, in part, will be used to establish a dedicated human resource capacity to review the safety, efficacy and quality aspects of products to be exported under the General Council Decision. This will ensure that domestic review times of pharmaceutical products are not negatively impacted as well as facilitate faster access of products under this program. It is not anticipated that the additional requirement for distinguishing features will require significant additional review times for Health Canada reviewers.

A workshop to discuss unique markings and the submission process was held with generic manufacturers who expressed an interest in participating in the program in mid-December 2003. Consultation with representatives of the brand manufacturers was also undertaken in December 2003.

Stakeholders were consulted regarding the optimal method of identifying the product. To provide a consistent and recognizable identification, it was decided that a standard marking would be prescribed in the Regulations. The letters "XCL" would be permanently marked on all solid dosages and on the immediate container of all non-solid dosages. Additionally, all labels would contain the "XCL" identifier and "FOR EXPORT UNDER THE GENERAL COUNCIL DECISION. NOT FOR SALE IN CANADA.", in either English or French.

The actual method used to mark the product was left to the discretion of the manufacturer, provided that it is permanent and does not alter the safety or efficacy of the drug. This flexibility allows manufacturers to employ new technologies as they become available, while preserving the integrity of the product and ensuring the identifying mark is present. Manufacturers are required to inform the Minister of Health of the method used to mark the product.

During the legislative process of Bill C-9, major stakeholders were provided with the opportunity to make representation and provide written submissions to the House of Commons Standing Committee on Industry, Science and Technology, the Senate Standing Committee on Foreign Affairs and government officials.

During the month of July 2004, consultations on the proposed Regulations were conducted with Canada's Research-Based Pharmaceutical Companies (Rx&D;), the Canadian Generic Pharmaceutical Association (CGPA), and non-governmental organizations.

Some stakeholders were of the opinion that the distinguishable features requirements needed to be more stringent, in order to avoid diversion of products. While this program needs to ensure that the requirements under the General Council Decision have been met and anti-diversion measures are present, the distinguishable features requirements cannot be too burdensome for manufacturers. The pre-export requirements, the Web site containing details of the products (e.g. quantity) that the manufacturer must develop and maintain (a requirement under the Patent Act), and the distinguishing features as discussed above all act to serve as anti-diversion measures.

Other stakeholders indicated some concern respecting distinguishing features requirements. For example, the requirement to have a significantly different colour from the product on the Canadian market becomes problematic for a manufacturer when it is required to provide evidence that the colour does not affect the safety and efficacy of the product. It should be noted that manufacturers, under the current regulations, must provide evidence that the colour used, and any markings on the product, do not alter the safety and efficacy of the product.

It was also noted that the requirement to notify the Minister of Health prior to the manufacturing of each lot may be too onerous for manufacturers. In order to ensure that Health Canada upholds the anti-diversion requirements under the General Council Decision, it is important that the Health Products and Food Branch Inspectorate is notified in a timely manner of a manufacturer's intent to begin manufacturing. This allows the Inspectorate the opportunity to conduct pre-export inspections in order to ensure that the product is in compliance with the requirements under the Food and Drugs Act and its regulations, and that the product will not be diverted.

This amendment does not alter existing compliance mechanisms under the provisions of the Food and Drugs Act and Regulations enforced by the Health Products and Food Branch Inspectorate. The Inspectorate has committed to inspecting the products prior to initial exportation. As such, there is a provision in the proposed Regulations which requires the manufacturer to notify the Minister of Health 15 days prior to the manufacturing of each lot. This proposal is included in order to provide the Inspectorate with adequate time to schedule an inspection if necessary.

Dr. Robert Peterson, Director General, Therapeutic Products Directorate, Health Product and Food Branch, Department of Health, 1600 Scott Street, 6th Floor, Address Locator 3106B, Ottawa, Ontario K1A 0K9, (613) 957-0368 (telephone), (613) 952-7756 (facsimile), C9@hc-c.gc.ca (electronic mail).

Notice is hereby given that the Governor in Council, pursuant to section 30 (see footnote a) of the Food and Drugs Act, proposes to make the annexed Regulations Amending the Food and Drug Regulations (1402 — Drugs for Developing Countries).

Interested persons may make representations with respect to the proposed Regulations within 75 days after the date of publication of this notice. All such representations must cite the Canada Gazette, Part I, and the date of publication of this notice, and be addressed to Dr. Robert Peterson, Director General, Therapeutic Products Directorate, Health Products and Food Branch, Department of Health, Address Locator No. 3106B, 1600 Scott Street, Holland Cross, Tower B, 6th Floor, Ottawa, Ontario K1A 0K9 (tel.: (613) 957-0368; fax: (613) 952-7756; e-mail: C9@hc-sc.gc.ca).

Persons making representations should identify any of those representations the disclosure of which should be refused under the Access to Information Act, in particular under sections 19 and 20 of that Act, and should indicate the reasons why and the period during which the representations should not be disclosed. They should also identify any representations for which there is consent to disclosure for the purposes of that Act.

REGULATIONS AMENDING THE FOOD
AND DRUG REGULATIONS (1402 — DRUGS
FOR DEVELOPING COUNTRIES)

1. Part C of the Food and Drug Regulations (see footnote 1) is amended by adding the following after Division 6:

"Commissioner of Patents" means the Commissioner of Patents appointed under subsection 4(1) of the Patent Act. (commissaire aux brevets)

"General Council Decision" has the meaning assigned by subsection 30(6) of the Act. (décision du Conseil général)

C.07.002. This Division applies to the sale of drugs for the purposes of implementing the General Council Decision.

C.07.003. An application by a manufacturer for authorization to sell a drug under this Division shall be submitted to the Minister and shall contain the following information and documents:

(a) a statement that the manufacturer intends to file an application with the Commissioner of Patents under section 21.04 of the Patent Act;

(b) in respect of a new drug, the submission number and date of filing of the new drug submission or abbreviated new drug submission filed under section C.08.002 or C.08.002.1, respectively, and of any supplement filed under section C.08.003 in respect of the drug;

(i) the application number and date of filing of the application that has been filed under section C.01.014.1 in respect of the drug, or

(ii) the drug identification number, if one has been assigned in respect of the drug pursuant to section C.01.014.2;

(d) for a drug in a solid dosage form, the manner in which the drug is marked in accordance with paragraph C.07.008(a) and evidence that such manner does not alter the safety and efficacy of the drug;

(e) for a drug in a dosage form that is not solid, the manner in which the immediate container is marked in accordance with paragraph C.07.008(a); and

(f) a sample of the label for the drug that includes the information required by paragraph C.07.008(c).

C.07.004. The Minister shall notify the manufacturer and the Commissioner of Patents for the purposes of paragraph 21.04(3)(b) of the Patent Act that the manufacturer's drug meets the requirements of the Act and these Regulations if

(a) the manufacturer has submitted to the Minister an application in accordance with section C.07.003 and a copy of the application filed by the manufacturer with the Commissioner of Patents under section 21.04 of the Patent Act;

(b) in respect of a new drug, an examination of the new drug submission or abbreviated new drug submission or supplement to either submission by the Minister demonstrates that the submission or supplement complies with section C.08.002, C.08.002.1 or C.08.003, as the case may be, and section C.08.005.1;

(c) in respect of a drug that is not a new drug, a drug identification number has been assigned pursuant to section C.01.014.2; and

(d) the Minister is satisfied that the manufacturer and the drug comply with the Act and these Regulations.

C.07.005. Despite sections C.01.014, C.08.002 and C.08.003, a manufacturer may sell a drug under this Division if

(a) the Minister has notified the Commissioner of Patents for the purposes of paragraph 21.04(3)(b) of the Patent Act that the drug meets the requirements of the Act and these Regulations; and

(b) the manufacturer has received authorization under section 21.04 of the Patent Act.

C.07.006. Sections C.01.005 and C.01.014.1 to C.01.014.4 do not apply to new drugs sold under this Division.

C.07.007. The Minister shall notify the manufacturer and the Commissioner of Patents for the purposes of paragraph 21.13(b) of the Patent Act in the event that the Minister is of the opinion that the manufacturer's drug authorized to be sold under this Division has ceased to meet the requirements of the Act and these Regulations.

(a) the drug itself permanently bears the mark "XCL", in the case of a drug in a solid dosage form, or the immediate container permanently bears the mark "XCL", in the case of a drug in a dosage form that is not solid;

(b) the colour of the drug itself is significantly different from the colour of the version of the drug sold in Canada, in the case of a drug in a solid dosage form; and

(c) the label of the drug permanently bears the mark "XCL", followed by the export tracking number assigned by the Minister under section C.07.009 and the words "FOR EXPORT UNDER THE GENERAL COUNCIL DECISION. NOT FOR SALE IN CANADA." or "POUR EXPORTATION AUX TERMES DE LA DÉCISION DU CONSEIL GÉNÉRAL. VENTE INTERDITE AU CANADA.".

C.07.009. The Minister shall assign an export tracking number to each drug in respect of which the Minister has notified the Commissioner of Patents under section C.07.004.

C.07.010. The manufacturer shall, with respect to a drug authorized to be sold under this Division,

(a) establish and maintain records, in a manner that enables an audit to be made, respecting the information described in section C.08.007; and

C.07.011. The manufacturer shall notify the Minister in writing not less than 15 days prior to commencing the manufacture of each lot of a drug authorized to be sold under this Division.

2. These Regulations come into force on the day on which An Act to amend the Patent Act and the Food and Drugs Act (The Jean Chrétien Pledge to Africa), being chapter 23 of the Statutes of Canada, 2004, comes into force.