In vitro dissolution testing is commonly performed to ensure that oral solid dosage medicines are of high quality and will achieve their targeted in vivo performance. However, this testing is time and material consuming. Therefore, pharmaceutical companies have been developing predictive dissolution models (PDMs) for drug product release based on fast at- and/or on-line measurements, including real-time release testing of dissolution (RTRT-D). Recently, PDMs have seen acceptance by major regulatory bodies as release tests for the dissolution critical quality attribute. In this paper, several methodologies are described to develop and validate a fit-for-purpose model, then to implement it as a surrogate release test for dissolution. These approaches are further exemplified by real-life case studies, which demonstrate that PDMs for release are not only viable but more sustainable than in vitro dissolution testing and can significantly accelerate drug product release. The rise of continuous manufacturing within the pharmaceutical industry further favors the implementation of real-time release testing. Therefore, a steep uptake of PDMs for release is expected once this methodology is globally accepted. To that end, it is advantageous for global regulators and pharmaceutical innovators to coalesce around a harmonized set of expectations for development, validation, implementation, and lifecycle of PDMs as part of drug product release testing.

Analytical Commercialization Technology Merck and Co Inc 126 E Lincoln Ave Rahway NJ 07065 United States of America

Analytical Development Pharmaceutical Sciences Takeda Cambridge MA 02139 United States of America

Global Product Development Pharmaceutical Technology and Development Operations AstraZeneca Gothenburg Sweden

Janssen Pharmaceutica NV Beerse Belgium

Janssen Supply Chain Johnson and Johnson New Brunswick NJ United States of America

Manufacturing and Applied Statistics Janssen Cilag S R O Prague Czechia

Manufacturing and Applied Statistics Janssen Pharmaceutical R and D LLD Raritan NJ 08869 United States of America

Synthetic Molecule Design and Development Eli Lilly and Company Indianapolis IN 46285 United States of America

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