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Near-infrared spectroscopy in the pharmaceutical industry

Near-infrared spectroscopy in the pharmaceutical industry
Near-infrared spectroscopy in the pharmaceutical industry

Efficient process monitoring and quality control with near-infrared in the pharmaceutical process chain.

The amount and variety of work in the quality control laboratories of the pharmaceutical industry have risen in recent years and will continue to increase in the future. Increasing requirements for process monitoring imposed by gov- ernmental authorities on the one hand and economic aspects on the other, the quality control laboratories are forced to find and establish more efficient technologies. This poses a challenge to the entire pharmaceutical industry.

Near-infraredspectroscopy(NIRS)
There is a wide range of applications for near-infrared spectroscopy (NIRS) in the pharmaceutical industry, and it has been in use since the 1950s. In NIRS, the transmission, reflection or transflexion of the analyte is recorded using wavelengths in the near-infrared region of the electromagnetic spectrum, between 780 and 2500 nm. The spectra consist of overtone and combination bands created by exciting covalent bonds (e.g. CH, OH or NH), which are interpreted and analyzed quantitatively and qualitatively using chemometric software.

 

Advantages of NIRS
NIRS is a robust, contactless, non-destructive, non-invasive and fast measuring process that can be easily automated and requires little or no sample preparation. NIRS can be used during manufacturing processes (on-line), with portable devices (at-line) or with stand-alone devices (off-line).

 

Disadvantages of NIRS
In the GMP environment, due to the high number of samples, complex calibration and validation procedures must be carried out before NIRS can be used; a validated reference method is required. A computer system validation (CSV) is also necessary due to the use of chemometric software.

 

Qualitative calibration and application
For an identity check using NIR, a spectral library of various molecules is created and the corresponding identities are assigned to the individual spectra. Chemometric tools such as principal component analysis (PCA) enable users to identify the molecules contained in the spectral library. The qualitative calibration is not difficult, as the data are collected using simple measurements (e.g. IR). In practice, the identity of a product can already be checked upon arrival at the manufacturing site even by minimally trained personnel, e.g. at-line on the truck. This improves the monitoring of the transport and the logistics of the raw materials, as the confirmed identity of the raw materials permits them to be added to the process chain on a just-in-time basis.


Quantitative calibration and application
Quantitative calibration of NIRS is significantly more complex. First, spectra are recorded as in qualitative calibration. Subse- quently, the desired quality parameters of the analyte are analyzed using a reference method (e.g. determination of water Calibration Data selection Generation of a calibration model Data recording Calibration Validation Measurement using the reference method content using Karl Fischer titration) and the result obtained is assigned to the spectrum. Data are collected across the entire calibration range and a calibration model is established by means of analysis using chemometric tools (such as multiple linear regression). This calibration model can then be used to measure the water content of the analyte. Parallel analysis of a larger number of samples using NIRS and a reference method is required to cover the entire calibration range – in this example the determination of the water content using Karl Fischer titration. This makes the calibration of an NIR instrument very time-consuming, as 100-150 samples are commonly analyzed for this purpose. In the regulated environment of pharmaceuti- cal manufacturing, the validation of this calibration model is also required, which further increases the analytical and temporal effort involved in the calibration of an NIR instrument. This is balanced by the benefits: using an NIR instrument reduces the time required for analyzing water content with Karl Fischer titration from several minutes to just a few seconds and facilitates on-line monitoring of the water content of granulates used to manufacture tablets, for example.

Conclusion
NIR technology can be used in all areas of a product’s process chain, from the initial inspection of the raw material to monitoring of the manufacturing process and the final inspection as well as the delivery of the medication. The calibration and validation of an NIR instrument are complex and time-consuming, but justified by the huge benefits, particularly in process monitoring (process analytical technology [PAT]) and quality control (QC). NIR technology is not yet firmly established in the pharmaceutical industry (in contrast to the food industry), but will become increasingly important due to the governmental initiatives in the area of continuous process improvement (CPI). Near-infrared technology has the potential to become a key technology in PAT. Due to the increasing regulatory require- ments for making processes more controllable, in the medium term the industry will replace in-process analysis by process-monitoring analysis in order to achieve better equipment and resource utilization and reduce costs via real-time release and continuous process verification. Chemgineering possesses in-depth expertise in method development, calibration and validation (including CSV) and will be pleased to support you with any questions you may have about the use of NIR spec- troscopy. Simply contact us on an informal basis whenever you need advice.

 

Heiko Jencio|Senior Consultant Pharmaceutical Compliance|Chemgineering - The Business Designers

 

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