Health Canada Addresses Concerns in Trial Application Guidance
14 May 2009
Clinical Trials Advisor

Sponsors should submit increasingly detailed information as their clinical trials move through the various phases, according to Health Canada’s final guidance on preparing clinical trial applications (CTAs).

The new guidance addresses both chemistry and manufacturing technical requirements for Phase I, II and III clinical trials. The guidance includes a set of three quality overall summary (QOS) templates to assist sponsors in meeting specifications in each phase. Submissions for combination protocols — Phase I/II or II/III — should satisfy the quality requirements of the higher phase, the guidance says.

The QOS templates follow a common format, which includes the following:

* Introduction;

* Drug substance (general information, manufacture, characterization, control of drug substance, container closure system and stability); and

* Drug product (description and composition of the drug product, pharmaceutical development, manufacture, control of excipients, control of drug product, container closure system and stability).

Sponsors “may cross-reference all quality information to previously approved CTAs provided they are of the same or higher phase (e.g. Phase III CTAs cannot be fully cross-referenced to Phase II CTAs but may be cross-referenced to approved Phase III CTAs), with the exception of the drug product batch analysis for Phase I and Phase II clinical trial applications,” the guidance says.

A revised draft version of the guidance issued in April 2008 elicited 135 comments. Stakeholders commented on topics from good manufacturing practice requirements in Phase I trials to clarification about the type of information requested in the new templates, Health Canada says.

Changes to the final document include removal of a section on manufacturing process development in the Phase III template and the use of more consistent language across all three templates, the agency says. The Phase III template was revised to eliminate duplicate reporting of information and simplify the submission process.

The guidance takes effect June 1. However, companies are encouraged to begin using the new “Quality Summary — Chemical Entities” templates now. After June 1, the agency will notify potential sponsors that use of other formats may lead to comments and requests for clarification when the submission is reviewed.

Alternate approaches may be acceptable, the guidance says, provided they are backed by adequate scientific justification. Sponsors should discuss plans to use an alternate approach with the agency before submitting an application.

“Quality (Chemistry and Manufacturing) Guidance: Clinical Trial Applications (CTAs) for Pharmaceuticals” can be accessed at www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/qual_cta_dec-eng.pdf.