BEBAC  Ing. Helmut Schütz

Bioequivalence Requirements: Critical Dose Drugs

Canada – HPFB

On 31 May 2006 Canada’s HPFB published a ‘Guidance for Industry. Bioequivalence Requirements: Critical Dose Drugs’.

The category of ‘Critical Dose Drugs’ is intended to replace the categories of narrow therapeutic range drugs and highly toxic drugs defined in Report C of the Expert Advisory Committee on Bioavailability and Bioequivalence (1992).

The guidance includes additional clarification as a result of comments that have been received (where appropriate) as well as to promote consistency with other Health Canada guidance documents.

Appendix I of the guidance provides a list of critical dose drugs, namely: cyclosporine, digoxin, flecainide, lithium, phenytoin, sirolimus, tacrolimus, theophylline, and warfarin.

The guidance is effective with 31 May 2006.


The guidance is superseded by two guidances issued on 22 May 2012: