Post-market surveillance is a key regulatory function to prevent substandard and falsified (SF) medicines from being consumed by patients. Field deployable technologies offer the potential for rapid objective screening for SF medicines.
Methods and findings
We evaluated twelve devices: three near infrared spectrometers (MicroPHAZIR RX, NIR-S-G1, Neospectra 2.5), two Raman spectrometers (Progeny, TruScan RM), one mid-infrared spectrometer (4500a), one disposable colorimetric assay (Paper Analytical Devices, PAD), one disposable immunoassay (Rapid Diagnostic Test, RDT), one portable liquid chromatograph (C-Vue), one microfluidic system (PharmaChk), one mass spectrometer (QDa), and one thin layer chromatography kit (GPHF-Minilab). Each device was tested with a series of field collected medicines (FCM) along with simulated medicines (SIM) formulated in a laboratory. The FCM and SIM ranged from samples with good quality active pharmaceutical ingredient (API) concentrations, reduced concentrations of API (80% and 50% of the API), no API, and the wrong API. All the devices had high sensitivities (91.5 to 100.0%) detecting medicines with no API or the wrong API. However, the sensitivities of each device towards samples with 50% and 80% API varied greatly, from 0% to 100%. The infrared and Raman spectrometers had variable sensitivities for detecting samples with 50% and 80% API (from 5.6% to 50.0%). The devices with the ability to quantitate API (C-Vue, PharmaChk, QDa) had sensitivities ranging from 91.7% to 100% to detect all poor quality samples. The specificity was lower for the quantitative C-Vue, PharmaChk, & QDa (50.0% to 91.7%) than for all the other devices in this study (95.5% to 100%).
The twelve devices evaluated could detect medicines with the wrong or none of the APIs, consistent with falsified medicines, with high accuracy. However, API quantitation to detect formulations similar to those commonly found in substandards proved more difficult, requiring further technological innovation.
Criminally falsified or poorly manufactured medicines can lead to patients becoming sicker and losing trust in the health system. Portable tools beyond just documentation checks and visual inspection (the current practices in many low- and middle-income countries) can help pharmacy inspectors with early detection of poor quality medicines. Currently, many tools are available to detect poor quality medicines, but their performances have not been properly assessed and compared. In this study, 12 different devices ranging from disposable single use tests to portable spectrometers were tested in a laboratory. All the tested devices could identify medicines that contained none or the wrong active ingredient(s), a common trait of falsified medicines. Disposable tests required few resources to be implemented, but had difficulties identifying medicines with reduced amounts of active ingredients. Spectrometers used ‘out-of-the-box’ required minimal consumables had varying degrees of success at detecting medicines with reduced amounts of active ingredients. Finally, instruments with more quantitative abilities, such as benchtop simple chromatographs or mass spectrometers, offered the best sensitivity for detecting medicines with reduced amounts of active ingredients, but required the most resources and training and were deemed to be more suitable for centralized testing.