The problem that was investigated in this work concerned the time and effort associated with raw material identification tests at Aspen, a pharmaceutical manufacturer in Port Elizabeth, South Africa. The main problems associated with current raw material identification practices at Aspen is that all raw materials need to be sampled, in isolated sampling rooms, transported to the analytical testing laboratory, and samples prepared for analysis before the actual identification test could be run, irrespective of the actual method used for identification. Spectroscopic raw material identification using a handheld Raman analyser appeared to be an attractive option, not only from an instrument cost point of view, but from a time-saving point of view since samples could be tested in-situ in their original packaging, provided such packaging are transparent to the particular wavelengths of light.
The investigation was carried out by performing different identification tests using typical pharmaceutical method validation parameters as guideline to establish whether the handheld Raman analyser would meet Aspen’s regulatory requirements. Only one specific molecule, namely paracetamol, was selected for the purpose of the evaluation and raw material samples were subjected to identification tests under a variety of conditions. These included the identification of the raw material supplied by different suppliers, the same supplier but material of the same manufacturing batch packed into different containers, and raw materials subjected to different storage conditions. In addition, a specificity test was also carried out in which a sample of paracetamol raw material was deliberately contaminated with either acetanilide, or 4-aminophenol, or both at varying concentration levels.
The results obtained from these investigations showed that the handheld Raman analyser can correctly identify the selected raw material (paracetamol) under a wide range of conditions as mentioned above. The one area of concern is in terms of specificity where to analyser could not correctly identify the presence of the selected contaminants at lower concentration levels (< 10 – 20 mass %). More detailed test can obviously be carried out in this regard if it is of specific concern,
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but in the present case, none of the selected contaminants (which were selected on the basis of their molecular resemblance to paracetamol) are known contaminants for paracetamol.
Finally, a cost-benefit analysis was carried out in which a scenario in which an existing FTIR-ATR system is used for the analysis of a specific number of raw material samples per year as opposed to a scenario in which a new handheld Raman analyser has to be purchased, set up, and used for the analysis of the same number of raw material samples. This comparison showed that the handheld Raman analyser had a pay-back time of approximately 6 months and gave a return on investment of approximately the same value as the actual purchase cost. Given the findings of this work, Raman spectroscopy using handheld Raman analysers should be considered for wide introduction in the Aspen raw material testing divisions at its different manufacturing sites.
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