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B. Igne and E. W. Ciurczak
18.1 Introduction
The pharmaceutical industry aims to discover, develop, and manufacture chemical
and biological compounds with a therapeutic activity that benefits patients. These
active pharmaceutical ingredients (APIs) can be synthetized by synthetic chemical
reactions (small molecules) or natural processes through the use of microorganisms
(large molecules). After an entity has been found to have a desired therapeutic effect
and is approved for sale by health authorities, it needs to be manufactured in sufficient
quantity to ensure patient access.
Since the first applications of near-infrared spectroscopy (NIRS) in the pharmaceutical industry [1] to today’s in-line and in real-time monitoring and control of
manufacturing processes, the technology has come a long way in sensitivity, robustness, and deployability. While that evolution was inevitable, it still took several
decades to demonstrate the value the technology can bring to ensure product quality.
In this chapter, an overview of the current uses of near-infrared spectroscopy will
be provided for the development, understanding, and control of pharmaceutical
processes for small molecule drug substances, drug products, and biopharmaceutical
materials.
While an active field of research and development in the 1980s and 1990s, it is
the US FDA that put NIRS and other rapid, non-destructive analytical tools on the
map of senior stakeholders with the Process Analytical Technology (PAT) guidance
of 2004 [2]. It defined Process Analytical Technologies as “a system for designing,
analyzing, and controlling manufacturing through timely measurements (i.e. during
processing) of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality” [2]. While NIRS is
certainly not the only process analytical tool, it is one of the most robust, the safest,
and most widely used tool by pharmaceutical scientists. The reasons are multiple
(i.e., good sample penetration depth, no sample preparation, rapid acquisition, and
good sensitivity), but the combination of spectroscopy and chemometrics led to the
development of NIRS as a technology of choice and to the training of a generation of
process analytical scientists, skilled in spectroscopy, chemometrics, sampling, and
engineering. It is nevertheless important to note that much work has been done with
IR, Raman, fluorescence, and UV–Vis spectroscopy. Readers can get an idea of the
current state of the process analytics field in several reviews [3, 4].
In this chapter, an overview of the current usages of NIR Spectroscopy in the pharmaceutical industry for small and large molecules will be presented. For a historical
perspective, readers should refer to other books and book chapters [5–7].
B. Igne and E. W. Ciurczak
18.1 Introduction
The pharmaceutical industry aims to discover, develop, and manufacture chemical
and biological compounds with a therapeutic activity that benefits patients. These
active pharmaceutical ingredients (APIs) can be synthetized by synthetic chemical
reactions (small molecules) or natural processes through the use of microorganisms
(large molecules). After an entity has been found to have a desired therapeutic effect
and is approved for sale by health authorities, it needs to be manufactured in sufficient
quantity to ensure patient access.
Since the first applications of near-infrared spectroscopy (NIRS) in the pharmaceutical industry [1] to today’s in-line and in real-time monitoring and control of
manufacturing processes, the technology has come a long way in sensitivity, robustness, and deployability. While that evolution was inevitable, it still took several
decades to demonstrate the value the technology can bring to ensure product quality.
In this chapter, an overview of the current uses of near-infrared spectroscopy will
be provided for the development, understanding, and control of pharmaceutical
processes for small molecule drug substances, drug products, and biopharmaceutical
materials.
While an active field of research and development in the 1980s and 1990s, it is
the US FDA that put NIRS and other rapid, non-destructive analytical tools on the
map of senior stakeholders with the Process Analytical Technology (PAT) guidance
of 2004 [2]. It defined Process Analytical Technologies as “a system for designing,
analyzing, and controlling manufacturing through timely measurements (i.e. during
processing) of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality” [2]. While NIRS is
certainly not the only process analytical tool, it is one of the most robust, the safest,
and most widely used tool by pharmaceutical scientists. The reasons are multiple
(i.e., good sample penetration depth, no sample preparation, rapid acquisition, and
good sensitivity), but the combination of spectroscopy and chemometrics led to the
development of NIRS as a technology of choice and to the training of a generation of
process analytical scientists, skilled in spectroscopy, chemometrics, sampling, and
engineering. It is nevertheless important to note that much work has been done with
IR, Raman, fluorescence, and UV–Vis spectroscopy. Readers can get an idea of the
current state of the process analytics field in several reviews [3, 4].
In this chapter, an overview of the current usages of NIR Spectroscopy in the pharmaceutical industry for small and large molecules will be presented. For a historical
perspective, readers should refer to other books and book chapters [5–7].