Biowaiver monographs for immediate-release solid oral dosage forms: Voriconazole

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Biopharmaceutics

Background:

• Voriconazole is classified as a Biopharmaceutics Classification System (BCS) class II drug per ICH M9 guidelines.
• This classification is due to its high solubility at the highest dose strength but not at the highest single dose.
• Voriconazole does not meet the dose-proportional pharmacokinetics (PK) requirement for BCS-based biowaivers under ICH M9.

Purpose of the Study:

• To evaluate the appropriateness of the ICH M9 Guideline's biowaiver eligibility criteria for voriconazole.
• To discuss potential revisions to biowaiver guidelines to accommodate drugs with similar characteristics to voriconazole.
• To explore alternative classification systems and testing methods for biowaiver considerations.

Main Methods:

• Review of the ICH M9 Guideline and its application to voriconazole.
• Comparison of voriconazole's classification under current ICH M9 criteria versus prior FDA criteria.
• Analysis of voriconazole's in vitro dissolution profiles and correlation with clinical studies.
• Discussion of the refined Developability Classification System (rDCS) and biorelevant dissolution testing.

Main Results:

• Voriconazole would be BCS class I under pre-ICH M9 FDA solubility criteria, qualifying for a biowaiver.
• Rapid dissolution of the highest oral dose strength of voriconazole under all BCS conditions was observed.
• In vitro dissolution data for different tablet formulations correlated with demonstrated bioequivalence (BE) in clinical studies.
• The ICH M9 Guideline may be overly restrictive for voriconazole and similar drugs.

Conclusions:

• The current ICH M9 Guideline may unnecessarily restrict biowaiver approvals for certain drugs like voriconazole.
• Revisions to eligibility criteria, potentially incorporating systems like the refined Developability Classification System (rDCS) and biorelevant dissolution testing, are warranted.
• A more flexible approach could extend biowaiver approvals to a broader range of suitable drugs, streamlining development.