FDA's process analytical technology (PAT) initiative that asserts "quality cannot be tested into products, it should be built in or should be by design" has generated a large amount of interest in new technologies for pharmaceutical analysis.^1,2 A key aspect of FDA's PAT philosophy is that every stage of the manufacturing process should be monitored and understood so that the end product is right first time, every time. In practice, the implementation of this philosophy will require a range of analytical tools capable of operating throughout the manufacturing process: at-line, on-line and in-line.

These technologies must be capable of generating detailed, meaningful results in real time, which may be fed back into the control mechanisms of the process to ensure the final product quality is consistently maintained. Near infrared (NIR) spectroscopy has been widely discussed and applied in this role.³ Raman spectroscopy also has great potential in this application and has indeed formed part of FDA's PAT initiative education programme¹ and reports are now beginning to appear in the literature discussing Raman's application as a PAT-type tool.^4–8

Benefits for PAT Applications The Raman effect was first observed in 1928 by C.V. Raman⁹ and has been extensively studied and applied, generating an enormous body of scientific literature. This superior scientific foundation enables a deeper, molecular level understanding of the manufacturing process and gives confidence to both the manufacturer and the regulatory authorities in the value of this technique.

Figure 1: An example of the use of Raman spectroscopy to determine the component concentrations in a binary solvent mixture.

Figure 2: Comparison of (a) IR absorption and (b) Raman spectra for an aqueous suspension/solution of an API.