Canadian GMP Regulations

Division 2, Part C of the Food and Drug Regulations is not a title that immediately springs to the lips of participants in the Canadian pharmaceutical industry. Sub-title it "Good Manufacturing Practices Regulations or GMP" and the recognition is immediate. The Canadian GMPs have come a long way from the use of the original Department of Supply and Services document 74 GP-1 e (the DSS drug purchasing specifications ), which guided the HPB inspectors in their evaluation of a company's production facilities. The inevitable inclusion of the GMP in the Food & Drug Regulations and the subsequent issue of the First Edition of the GMP "Blue Guide" finally heralded the era of legal GMP requirements.

Since then, the guidelines have changed from the "Blue Guide" to the "Gray Guide", and now the official Fourth Editionof the GMP Guidelines is about to be fully launched upon the industry in the new year. The question naturally arises as to "what is the impact of this 4th Edition?" Is this a case of more of the same, and everything goes on as usual? The answer that question is a definitive no!

Among the major initiatives planned for 1996 in HPB's Business Plan is the proposal that all manufacturer's of drugs listed in Schedules C and D comply with the requirements of Division 2 of the Food & Drug Regulations. As a condition for the issuance and continuation of a licence, the department will conduct periodic on-site inspections of such manufacturing facilities to ensure adherence to GMP. The recent GMP guidelines note in the introduction that, beginning with the Fourth Edition, there will be appearing for the first time, a series of separate appendices. Appendices being considered for separate publishing, include active pharmaceutical ingredients, investigational drug products, radiopharmaceuticals, homeopathics, herbals and biologics. This is in addition to other guidelines being planned for process validation and cleaning validation.

What this means for companies is that training in the application of the new written interpretations is going to be fundamental in maintaining compliance with the inevitable new inspectional approaches. This can be most readily seen in the expanded interpretation sections on Personnel, C.02.006. The two previous interpretation sections have been expanded by the addition of four new additional sections, the most relevant of all being the direct inclusion and elaboration of GMP training; including not only the requirement for a training programme to be carried out and documented by qualified personnel, but that there be a determination of effectiveness of the training by periodic assessment.

New areas for training are indicated by a glance at the "Glossary of Terms" section, which includes new terms not previously present, such as; Critical Process, In-Process Control, Installation Qualification, Operational Qualification, Recovery, Reprocessing, System, and Validation.

With the growing complexities of GMP compliance it behooves companies to ensure that they have viable training programmes in place, which are able to meet the demands of the new requirements. Those companies which in the past have sought to relegate the GMP training programmes to the Human Resources departments would do well to ensure that the administration and control of the necessary programmes be firmly placed within the Operations and Quality Assurance spheres of control.

United States Regulatory News
It would appear that recent intense pressure exerted on the FDA to accelerate the review of drug products is having some effect upon the Agency. A combination of Congressional threats to reform the Agency coupled with consumer group complaints of more drugs being available in other jurisdictions, has led to the FDA adopting a new attitude towards what it describes as "significant therapies". The current focus appears to be on the AIDS and Diagnostics areas. In fact, a new speed record (79 days after NDA submission) was set recently with a product approval for a protease inhibitor.

Following President Clinton's April announcement of the initiation of new FDA policies, there is evidence to suggest that something is happening in the way review processes are being conducted. A move has been made to accelerate some approval categories, particularly for products which demonstrate efficiency in cancer tumour shrinkage. The net result will be some reduction in clinical trial requirements allowing use of smaller and shortened studies. Furthermore, the Agency has announced the implementation of an "expanded access" policy, whereby cancer products approved in other countries could be made available in the US while they were still under study in the US. In addition, the Advisory Panels for cancer drugs will now include patients possessing first-hand experience with the types of cancer being discussed.

Further information on these changes is available from Columbia Pharma Consulting Services at (206) 557-9990, or send e-mail to cpcs@halcyon.com.

© 1997 CPCS, Inc.