The quality of drugs and drug products - Always guaranteed?

Abstract

To ensure the efficacy, safety, and quality of drugs, several national and international guidelines and regulatory requirements exist. The most important international regulatory framework for quality is the collection of the guidelines ICH Q1-Q14 (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use), which form the basis for the development and approval of medicinal products. Additionally, international and national pharmacopoeias and national regulatory authorities like Food and Drug Administration (FDA) and European Directory for the Quality of Medicines and HealthCare (EDQM) have to be considered during the lifecycle of a drug. Further, regular updates and optimization of processes and methods together with periodic audits and inspections of the manufacturing plants help to ensure compliance with the complex regulatory requirements for medicinal products. Although the pharmaceutical world seems to be very well regulated and controlled, several drug recalls per year have to be announced and conducted to remove defect products from the market and protect the patient from any potential health risk. This review article provides an overview of the most common reasons for such recalls presenting several historical and current cases with a detailed discussion of root causes. A specific focus lies on quality issues like drug degradation, impurity and nitrosamine contamination, lack of drug stability, occurrence and transformation of polymorphs, contamination with particulates and foreign matters, amongst others. The role of APIs, excipients and packaging will be discussed as well as the analytical challenges to detect, control and mitigate such quality issues. A final chapter will discuss the current situation and an outlook on emerging topics and future challenges for drug quality.

Keywords: International pharmacopoeias; Quality guidelines; Root causes of quality problems.