Current challenges in the detection and analysis of falsified medicines.

Falsified medicines affect public health all around the globe. Complex distribution routes, illegal online webshops and reuse of packaging materials make them hard to detect. In order to tackle this problem, detection methods for the recognition of suspicious medicines and subsequent confirmation of falsification by analytical techniques is required. In this review, we focus on the developments and challenges that existed in the last five years (2015-2020) in the detection and analysis of falsified medicines. These challenges might have not been solved yet or arisen with new types of falsifications, new analytical techniques or detection strategies. Detection of suspicious medicines starts with visual inspection of packaging materials. However, re-use of packaging materials and high-quality imitations complicate visual inspection. Recent developments in the analysis of packaging by microscopic and spectroscopic techniques such as optical microscopy, X-ray fluorescence, infrared spectroscopy and Raman spectroscopy or microscopy, in combination with multivariate analysis show promising results in the detection of falsified medicines. An ongoing big challenge in the analysis of falsified medicines is the affordability of analytical devices. Yet, recent reports showed that lower cost devices, such as Counterfeit Drug Indicator or Counterfeit Detection device version 3 show promising use in the detection of falsified medicines. Furthermore, combining the outcomes of different low-cost analytical techniques, such as Minilab, colorimetry and Counterfeit Drug Indicator significantly increased selectivity and sensitivity in the detection of falsified medicines. Also, recent developments make it possible to link a low-cost technique, such as TLC, to mobile phones. Proper training of personnel has shown room for improvement and remains a challenge, even for relatively simple techniques. With an increased use of analytical fingerprints, an upcoming challenge is the accessibility of the growing pool of data. There is also the need of validated reference libraries on both national and international levels. Developments of the last few years bring us a step closer in the fight against falsified medicines, however challenges remain in the worldwide accessibility of affordable, easily operable and sensitive techniques.