Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Q3D step 4: background, impact and consequences of an ICH guideline upon elemental impurities in drug products ***

Dr. Mirko Hechenberger (Abschlußjahr: 2015)

Summary
Language: English
In December 2014 the ICH published a new guideline with acronym Q3D, ready for implementation (Step 4). The guideline describes a risk-based approach to limit 24 elemental impurities in drug products.
This master thesis provides an introduction into the principles and the background of this new ICH guideline. It describes the key features of elemental impurities risk management, their classification, the toxicological assessment leading to daily exposure limits (permitted daily exposure, PDE) and its application to drug products in order to protect patients from exposure beyond biological safety.
Differences compared to pharmacopoeial entries and other guidelines like its European predecessor, the Guideline Specification Limits for Residues of Metal Catalysts or Metal Reagents are described. The implications of new limits and proposed methods to achieve compliance with the guideline Q3D for the pharmaceutical entrepreneur in Europe and in the US are depicted. Moreover, consequences for regulatory authorities and for patients are analysed and discussed.
In contrast to concerns raised by some parties beforehand, several albeit limited studies now show compliance with the new PDE values for the existing drug substance and products tested and also for most of the excipients. Nevertheless, there will be adaptations needed to comply with the new requirements. These improvements will further advance the safety for patients.
A big promoter of this new guideline, the pharmaceutical industry, was motivated by the prospect of international harmonisation. However, achieving this goal seems to lag still behind, as the new chapters in the United States Pharmacopeia do not completely match the expectations raised by the ICH.
Pages: 45