The requirement for pAUC assessment metrics for multiphasic modified-release formulations will be based on data available from various sources, including but not limited to peer-reviewed scientific literature and the approved Canadian labelling, as applicable. These standards will be applied in addition to those normally applied in the assessment of bioequivalence (i.e. Modified-release products with multiphasic plasma concentration profiles demonstrated to be integral to their therapeutic effect will be subject to standards on the partial area under the concentration versus time curve (p AUC), defined over a restricted time interval(s) after drug administration. Nature of and/or reason for change: Clarification of the standard Location (section, paragraph): Section 2.1.1.1 The relative mean minimum concentration (C min) at steady state of the test to reference formulation product should not be less than 80.0% inclusive.The relative mean C max at steady state of the test to reference formulation product should be within 80.0% to 125.0% inclusive.The 90% confidence interval of the relative mean area under the concentration versus time curve at steady state over the dosing interval (AUC tau) of the test to reference formulation product should be within 80.0% to 125.0% inclusive.Nature of and/or reason for change: Section was removed since urine data is no longer used for assessment of comparative bioavailability and the information is therefore no longer relevant. Location (section, paragraph): Table of contents and in the document Nature of and/or reason for change: Portions of this section were transferred to the guidance on the Conduct and Analysis of Comparative Bioavailability Studies since the information was more relevant to study design than to standards. Location (section, paragraph): Section 2.1.1.10 Sponsors are invited to consult with Health Canada. Some submissions may require more specific clarification of requirements. Nature of and/or reason for change: The document provides general guidance. “Health Canada invites sponsors to request written feedback from the Division of Biopharmaceutics Evaluation (DBE) or a pre-submission consultation meeting for more details or product specific guidance. Nature of and/or reason for change: Clarification of the standard.Ĭhange: Addition of the following sentence: Location (section, paragraph): Section 2.1 (a) The relative mean maximum concentration (C max) of the test to reference product should be between within 80.0% - 125.0% inclusive. Nature of and/or reason for change: This clarification covers cases where, for example, different pharmaceutical forms or chemical forms with the same active moiety are being compared, i.e., cases where comparative bioavailability is being assessed, as opposed to bioequivalence.Ĭhange: change the wording of the standards as follows: Location (section, paragraph): Section 1.3 “In cases where the products are not considered to be pharmaceutically equivalent, the data requirements and criteria outlined in this guidance apply for a determination of comparative bioavailability.”