ImageHealth Canada, the drug regulatory and health department of Canada, is finalising new guidelines for Drug Master Filings (DMFs) in accordance with the International Conference on Harmonisation (ICH) standards. Even as more generic companies from India, China and Eastern European countries are in a drug master filing spree, the authority is planning to incorporate Certificates of Suitability (CEPs) of European drug regulator to simplify filing process, it is learnt.

The department has issued a draft guideline in September incorporating revisions and terminology from ICH guidelines to bring in more clarity on the product details on Type I to Type IV DMFs. The guideline is currently in the stage of finalisation and would be ready for implementation in 2009, said Health Canada officials.

"There was approximately a 15 per cent increase in the number of DMF filings in the recent past. For the past five to six years, a large number of companies from India, China and Eastern Europe are filing DMFs with us aggressively. Through the revised guidelines, we are making sure that the filings are upto the international standards," said Dr Stephanie Parra, manager of generic drugs, Quality Division, Bureau of Pharmaceutical Sciences, Therapeutic Products Directorate (TPD), Health Canada.

The guidance document is a revised version of the guidance document Product Master Files published in 1994 which will replace the 1994 document when it is officially adopted. The draft guideline includes direction on biotechnological/biological products, veterinary drug products and natural health products in addition to pharmaceuticals. As per the officials, the administrative requirements and procedures in the guideline have been updated and clarified, and content requirements for all types of DMFs are more detailed or cross-referenced to relevant ICH and Health Canada guidelines.

Currently, more than 4000 DMFs have been submitted to Health Canada originating from 40 countries including US, Italy, Spain, Canada, China, India etc. Over 840 companies have submitted DMFs with the authority and more than 300 new DMFs are filed with Health Canada each year. Presenting the latest activities of TPD at the Drug Information Association (DIA) workshop on Pre-market Evaluation of Quality and Bioavailability, Dr Parra also said that the majority of the filings were on type I DMFs, which refers to the drug master filings for active pharmaceutical ingredients (APIs).

Upon implementation of new guidance, evidence of Good Manufacturing Practice compliance (cGMP) will be required for API manufacturers. The requirements for cGMP evidence and establishment licensing already apply to sites fabricating Schedule D (Biologic) Drug Substances.

The directorate is also in the process to incorporate the Certificates of Suitability (CEPs) issued by European Directorate for Quality of Medicines and Healthcare (EDQM) for the TPD's evaluation programme for drug substances. The incorporation is expected to reduce both review times and in the number of chemistry related deficiencies noted in the first cycle of review, added Dr Parra.

The use of CEPs in Canada is implemented in a phased manner wherein the first two phases deal with the examination of selected CEPs and change in internal review process. The TPD will start initiating the third phase of the project, where the drug substance manufacturers have new filing options including an option of filing a CEP in place of a DMF, within next three months. With this, the manufacturers can file either in the current routes including submission route and DMF route or through the CEP route. However, the TPD's project concern only CEPs for APIs even as the EDQM's CEP is for chemical purity and microbiological quality of substances for both APIs and excipients.

"Following further experience with the use of CEPs in TPD's review process it is expected that guidance on the full implementation of CEPs will provide drug submission sponsors with a new option of referencing a CEP in their submission, rather than referencing a DMF," according to a Health Canada announcement.

Besides, the TPD is also tightening the regulation for significant deficiencies noted during pre-evaluation of the 'closed' portion of DMF to seek more information from the DMF holder as the part of its effort to simplify the Abbriviated New Drug Submission (ANDS) approval through integrated review process (IRP). The well prepared DMF under the process will allow the ANDS filer to provide adequate information on the ingredients by referring the DMF document.