Non-invasive detection technologies of solid foreign matter and their applications to lyophilized pharmaceutical products: A review

Abstract

Good Manufacturing Practice Regulations, under the Food and Drug Administration (FDA), stipulate that all pharmaceutical products must be free of any contaminants, including, namely, any foreign solid objects. Lyophilization is a common manufacturing method that consists of several steps where foreign materials may enter the product. The presence of unintended particles in freeze drying, which will herein be referred to under the term ‘Lyophilization’, is of great concern to the authorities responsible for drug safety and effectiveness. In the pharmaceutical industry, presently, the inspection of lyophilized products for foreign matter particulates relies on visual inspection where only the outer surface of the lyophilized cake is visible. This review is motivated by the need for new control strategies for foreign matter (FM) detection in lyophilized products; more specifically, it assesses the reliability of non-destructive technologies for FM detection in dried samples. Emerging technologies applied in other industries, such as various types of spectroscopies and imaging (e.g. chemical, X-ray, ultrasound, thermal and terahertz), are evaluated based on compatibility with the intended application, with identification of the possible technical challenges.