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New developments in the pharmaceutical stress testing industry

A team of American scientists report on some recent developments in the realm of pharmaceutical stress testing, or forced degradation, practices relating to solid dosage forms, bringing some valuable clarity for drug developers.

Introduction

Stress testing, or forced degradation, has long been recognised by the pharmaceutical industry as an important part of the drug development process.1-5 Legislation6 and associated guidelines7,8 from the Brazilian regulatory authority (Agência Nacional de Vigilância Sanitária, or ANVISA) have introduced detailed regulatory requirements for forced degradation studies, including many requirements that are globally unique. For example, one requirement of RDC 53/2015 is that solution phase stress testing be conducted not only for drug substances, but also for drug products.

These are burdensome experiments to perform, since the design of the study is more complicated when the solid dosage form is exposed to solutions of low pH, high pH, oxidants and metal ions. Difficulties with extraction and dissolution of the active pharmaceutical ingredient (API) from the dosage form are more common with solid dosage forms, and such difficulties can lead to lack of mass balance and other complications. Additionally, providing justification for not performing these experiments has not always been accepted by ANVISA and pharmaceutical companies have had limited success in regulatory submissions without meeting these requirements.

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