Regulating Drug Packaging in Canada: DMF System Has Notable Differences
By Keller and Heckman LLP’s Packaging Practice Group
Canada's manner of regulating packaging materials for new drugs is substantially similar to the system used by the U.S. Food and Drug Administration. However, there are some notable differences between the two programs. This article briefly describes the system used by Health Canada's Therapeutic Products Programme to facilitate the review and evaluation of drug packaging materials to ensure the safety of their intended use in Canada, and notes the areas in which the Canadian system differs from FDA's procedure.
Similar to the situation in the United States, Canadian authorities do not have a mechanism for "clearing" or "approving" a particular material for use in drug packaging applications. Likewise, Health Canada's TPP does not maintain a master list of materials or components of materials that may be used in drug packaging applications in Canada. Instead, like in the United States, the Canadian authorities review and evaluate the safety of specific drug packaging materials during the course of the required review and approval of the finished new drug product that is packaged using the material of interest.
Canada's TPP utilizes a Drug Master File (DMF) system to facilitate the review of drug packaging materials. The DMF system also provides a vehicle for providing proprietary information about a packaging material directly to the authorities when the information, because of its confidential nature, is not available to the manufacturer of the finished dosage form.
A Canadian DMF, like a DMF submitted to the U.S. Food and Drug Administration's Center for Drug Evaluation and Research (CDER), is a submission that may be used to provide detailed information about facilities, processes, or articles used in the manufacture, processing, packaging, and storage of human drug products. A "Type II" DMF is used to supply information on drug packaging materials to the Canadian authorities, while under the U.S. system, drug packaging materials are covered in "Type III" DMFs.
The information contained in a DMF is referenced by TPP, upon authorization of the DMF holder, during the review of a pending drug submission to determine whether the drug packaging material is suitable for the intended use. The information is always maintained as confidential. A DMF holder may authorize as many customers to make reference to the DMF as is necessary. Thus, the DMF system offers the benefit not only of providing a means of supplying confidential information directly to the reviewing authorities, but also of relieving a packaging manufacturer of the need to make duplicate submissions to TPP on a given packaging material. Where no DMF has been established for a particular drug packaging material, the manufacturer of that material has the significant burden of providing manufacturing, compositional, and safety information about its product to its customer or to Health Canada for each drug submission that utilizes the drug packaging material.
TPP Guidelines are Instructional
DMFs are not required under Canadian law, and are submitted at the discretion of the holder. Thus, there are no legislative requirements in place regarding the information that must be included in a DMF. TPP has issued guidelines, however, to assist DMF holders in preparing and submitting complete and effective DMFs.
Typically, a DMF should include general information on the container and closure system, including the intended use of components, technical properties, acceptance specifications, and test methods for demonstrating compliance with these specifications. The file also should include specific information regarding the composition of the packaging material, information that would assist in determining whether any components may have toxic properties, results of any available migration studies, and results of tests for light and moisture transmission, where applicable. In addition, a DMF should include administrative information regarding the holder of the file and how the holder may be contacted.
While the premise behind TPP's DMF system and FDA's DMF system is the same, there are some noteworthy differences between the two systems.
- Significantly, Health Canada requires a $350 filing fee for each DMF that is registered with TPP. In addition, Health Canada requires a $50 fee for any letters subsequently submitted that authorize TPP to reference the DMF in connection with a particular drug submission. FDA has no similar fee requirements associated with the filing of and authorization to reference DMFs maintained with CDER.
- Both FDA and TPP require DMFs to contain statements confirming that the information contained in the DMF will be maintained as current -- a so-called "statement of commitment." In addition, FDA expects Type III DMFs to include a statement signed by the holder certifying that its facilities will be operated in compliance with all applicable environmental laws; TPP does not require a separate statement of "environmental compliance."
- Further, Health Canada's DMF guidance document facilitates the DMF holder's work in preparing a suitable file by providing model language to use in preparing a "statement of commitment," as well as model language for use in agent authorization letters (to allow the holder of a DMF to authorize an agent through which the DMF may be filed and amended), biannual update letters, and customer authorization letters (referred to as "letters of access" by TPP).
- Finally, Health Canada's system is slightly less demanding on the holder in that it requires that DMFs registered with Health Canada be updated only biannually (once every two years) to assure that the information contained in the DMF is current and accurate; DMFs maintained with FDA are required to be updated annually.
By making use of Health Canada's DMF system, manufacturers of drug packaging materials can assist TPP in its review of a drug submission while, at the same time, maintaining as confidential the information needed to assess whether a drug packaging material is suitable for the intended use. Understanding the information and administrative requirements of the Canadian DMF system – and making note of the ways in which this system differs from FDA's DMF program – will help to create a more complete and useful submission. Ultimately, this will facilitate Health Canada's drug review process and help bring a drug packaging material to market more quickly.