Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing

Karen A Esmonde-White,Ian R Lewis,Maryann Cuellar,Bruno Lenain,Carsten Uerpmann

doi:10.1007/s00216-016-9824-1

Karen A Esmonde-White, Ian R Lewis + Show 3 more

Open Access

https://doi.org/10.1007/s00216-016-9824-1

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Abstract

Adoption of Quality by Design (QbD) principles, regulatory support of QbD, process analytical technology (PAT), and continuous manufacturing are major factors effecting new approaches to pharmaceutical manufacturing and bioprocessing. In this review, we highlight new technology developments, data analysis models, and applications of Raman spectroscopy, which have expanded the scope of Raman spectroscopy as a process analytical technology. Emerging technologies such as transmission and enhanced reflection Raman, and new approaches to using available technologies, expand the scope of Raman spectroscopy in pharmaceutical manufacturing, and now Raman spectroscopy is successfully integrated into real-time release testing, continuous manufacturing, and statistical process control. Since the last major review of Raman as a pharmaceutical PAT in 2010, many new Raman applications in bioprocessing have emerged. Exciting reports of in situ Raman spectroscopy in bioprocesses complement a growing scientific field of biological and biomedical Raman spectroscopy. Raman spectroscopy has made a positive impact as a process analytical and control tool for pharmaceutical manufacturing and bioprocessing, with demonstrated scientific and financial benefits throughout a product’s lifecycle.

Highlights

Raman spectroscopy is an optical spectroscopy technique that provides a Bmolecular fingerprint^ of a sample
Raman spectroscopy as a tool for active pharmaceutical ingredients (API) analysis has been described for many applications, including polymorph identification, quantitative analysis, in situ crystallization monitoring, real-time release testing, pharmaceutical unit operations, and process-induced transformations [1,2,3,4,5]
Surface-enhanced Raman spectroscopy (SERS) can be a powerful tool for in-process measurements, and feasibility has been shown for SERS of bacterial analysis and in bioprocessing [98,99,100,101,102]

Summary

Introduction

Raman spectroscopy is an optical spectroscopy technique that provides a Bmolecular fingerprint^ of a sample. Wide area Raman spectroscopy of dapivirine in a polymeric controlled release device predicted API values, assessed initial process capability, and demonstrated that heterogeneous API distribution in the device would not affect product specifications [53] Another example of measuring spatial heterogeneity in API distribution was reported by BaronskyProbst et al where off-line Raman imaging was used to measure API distribution in a hot melt extrusion [54]. Recent research in Raman spectroscopy of fermentation bioprocesses have developed novel fiber optic probes and refined data analysis models, with the goal of in situ quantification of important parameters such as glucose, ethanol, and cell concentration. Raman spectroscopy has an important role in cell culture bioprocesses, providing in situ measurements and enabling real-time process control. We anticipate more basic research and applications incorporating novel chemometric models into bioprocessing, enabling even more sophisticated analyses

Conclusions

Findings

Compliance with ethical standards