Current Approaches for Dissolution Similarity Assessment, Requirements, and Global Expectations

Area of Science:

• Pharmaceutical Sciences
• Drug Product Quality Assessment
• Regulatory Science

Background:

• The 2019 M-CERSI workshop focused on In Vitro Dissolution Similarity Assessment for drug product quality.
• Regulatory agencies (FDA, HC, EMA, ANVISA) and industry discussed challenges with dissolution profile similarity for Chemistry, Manufacturing, and Control (CMC) changes.
• Current methods, like the f2 equation, have scientific shortcomings, and there's a need for improved assessment strategies.

Purpose of the Study:

• To summarize discussions on dissolution profile similarity assessment for minor/moderate CMC changes.
• To identify scientific shortcomings and areas of debate regarding dissolution testing methodologies.
• To explore opportunities for global harmonization in dissolution assessment strategies.

Main Methods:

• Summary of podium presentations and breakout sessions from the M-CERSI workshop.
• Discussion of experiences and concerns shared by regulatory agencies and the pharmaceutical industry.
• Analysis of debates surrounding dissolution timepoint variability, pairwise batch comparisons (PBC), and statistical methods.

Main Results:

• Dissolution profile similarity testing is part of a larger evidence-based assessment for CMC changes.
• Debate occurred on controlling timepoint variability and using PBC; industry suggested larger sample sizes and a single mathematical method.
• A majority favored using clinically relevant dissolution specifications (CRDS) and dissolution safe space over statistical similarity methods.

Conclusions:

• The workshop underscored the need for global harmonization in dissolution assessment, including variability, timepoint selection, and statistical methods.
• There is a clear preference for CRDS and dissolution safe space over traditional similarity assessment for evaluating CMC changes.
• Addressing ambiguity in dissolution assessment is crucial for globally operating pharmaceutical companies.