Economically-driven adulteration in the pharmaceutical global supply chain has led to significant deaths in recent years. Over 100 deaths in 2007 from cough syrup adulterated with ethylene glycol, 81 deaths and several hundred injured from over-sulfated chondroitin led to a recall of Heparinue in 2008, and recent milk product adulteration with melamine that affected pet food and baby formula have placed the industry under the spotlight of scrutiny.
The reasons are widespread; sourcing of raw material from developing economies, unregulated supply, and even the relabeling of source materials by distributors. Such practices resulted in complete reliance on the certificate of analysis as a means of material verification, increasing the risk of substandard materials in production and directly putting the consumer at risk. Mitigating that risk means implementing transparency between supplier and manufacturer through supplier audit and through the testing of incoming raw materials.
Several technologies can identify and quantify raw materials, most of which are punitive, need wet chemical or data from the primary method, requiring a library for identification and separate calibration curves for determining concentration levels.
Simultaneous Targeted and Non-Targeted Screening of Raw Materials for Impurities and Adulterants
Nuclear Magnetic Resonance (NMR) is a qualitative, structurally definitive technique that can confirm or deny molecular configuration(s). Quantitatively, peaks in an NMR spectrum are directly proportional to the number of nuclei (hydrogen, carbon, etc.), thus the integrated area under the peaks associated with the components of interest is proportional to the concentration of the material. The line shape of an NMR peak is laurentian signifying a means of fitting and accounting for total intensity. If adulterants, impurities or unknowns are present, the intensity of the additional spectral peaks correlated to concentration can be used to determine acceptability, delivering both a targeted and non-targeted approach to material screening. For the pharmaceutical industry, AssureTM-Raw Material Screening (RMS) brings a definitive technology (primary method) into the production environment.
Setting up Assure-RMS requires the one-off creation of a spectral reference library based on fully characterized materials using the same magnetic field strength and measurement parameters that will be used to verify incoming raw materials (additional materials can be added). The library includes the spectra and presence information (Chemical Shift) of the primary component, adulterants and impurities for each material, together with optimized acquisition method, enabling fully automated analysis under GLP or non-GLP operation.
An automated, customizable solution the Assure concept delivers accurate and reproducible results, achieved, in part, through a System Suitability Test (SST). Unique in the NMR industry, SST verifies performance by checking sensitivity, line shape and temperature stability, only proceeding to analyze when the SST is passed (frequency set to user’s SOPs).
The Assure-RMS package requires no previous NMR knowledge. Anyone working in a production QA/QC laboratory will find the interface uncomplicated; a few basic details, selection of a predefined fully-optimized analysis method and the sample can be submitted for analysis. Any pass or fail criteria is user-defined. The completed measurement generates two reports; a simple Pass/Fail QC report and an Expert Report, providing information about why the material passed (or failed), the relative concentrations of adulterants and impurities, and relative concentration of unknown material(s) and their possible matches from the reference library.
In conclusion, NMR has become a reliable, routine tool suitable for use in production environments by non-NMR experts. Assure-RMS is an automated, targeted and non-targeted screening tool delivering qualitative and quantitative reports operating in GLP/non-GLP environments using a definitive technology; addressing economically motivated adulteration for pharmaceutical raw materials.
