Industry-4-0-it 5 Aprile 2023

Raw material analysis and identification (RMID) using handheld NIR analyser Visum Palm™ assisted by AI

raw-material-pharmaceuticals
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Raw material analysis and identification (RMID) using handheld NIR analyser Visum Palm™ assisted by AI

The identification and raw material analysis (RMID) is a critical process in the pharmaceutical industry because it guarantees the identity and quality of all materials and substances to be used in the manufacturing process to ensure that they meet the specifications that the final products require to reach the consumer with the pharmacological characteristics for which they were designed.

In terms of raw material analysis, both Raman and NIR are complementary techniques and neither represents a final or definitive solution due to the large number of materials, substances and casuistries involved. For example, portable Raman analysers are sensitive to certain substances that emit fluorescence and are not the appropriate technique for moisture determination (LoD) to replace the Karl Fischer method or for the determination of the average particle size, where NIR spectroscopy is effective and at a lower cost.

Raw material analysis in the pharmaceutical industry

The Visum Palm™ portable NIR analyser is a self-contained spectrophotometer with embedded computer and touch screen that operates in the 900-1700 nm range useful for the identification, verification and classification of pharmaceutical raw material and has a spectral resolution of 256 pixels, a measuring area of 10 mm in diameter and 50 mm illumination, which allows obtaining more chemical information from the sample analysed and makes it more sensitive than other spectrophotometers to heterogeneities, even those derived from particle size for substances that are very similar. The analyser has an illumination system that shoots a large amount of light at the sample and a collection system that takes advantage of the greater amount of scattered light resulting from scattering, something to be taken into account especially when working with powdery substances.

analisis de materia prima analisis de materia prima

Among its particularities, it is the only NIR analyser on the market with AI-assisted software that allows any user, without specific technical knowledge in spectroscopy or multivariate data analysis, to develop their own NIRS libraries and methods and to edit them iteratively according to their needs, for example, to incorporate new substances or to strengthen a class with samples from a new supplier.

The Visum Master™ software in its GMP version has been specifically designed in compliance with the guidelines of the European Medicines AgencyGuideline on the use of near infrared spectroscopy by the pharmaceutical industry and the data requirements for new submissions and variations” (2014) and the Addendum “Defining the Scope of an NIRS Procedure” (2023). It is also FDA 21 CFR Part 11 compliant.

Figure 1: Visum Master™ GMP version software for pharmaceutical users.

Identification, verification and classification

The Visum Palm™ analyser allows the identification or verification analysis of different substances to be carried out in seconds by comparing the spectrum acquired from the sample with the average typical spectrum of each substance in the library. As a result of the raw material analysis, the Visum Palm™ analyzer provides the class with the highest similarity obtained (Figure 2) and lists the other substances in order of highest to lowest similarity.

Unlike the identification analysis, which is agnostic to the material to be inspected, the verification analysis (Figure 3) allows the user to select a specific substance within the library to confirm its identity. The result is either PASS or FAIL and, in the latter case, also indicates the correct substance with the highest similarity.

identification_verification

Figure 2: Identification                                                                   Figure 3: Verification PASS/FAIL

Classification analysis

In contrast to the above, for raw material analysis, classification (Figure 4) is a function that employs machine learning algorithms, not similarity, and allows to properly distinguish (classify) very subtle spectral differences, such as particle size or concentration of a particular analyte, even if they are the same API or excipient. It is a very useful function to identify anomalies in the raw material or to perform a confirmation of the identification analysis in problematic or doubtful cases where the substances are spectrally very similar, thus complementing the identification or verification analysis mentioned above.

In all the above cases, in addition to the result, the spectrum of the analysed substance is obtained for each measurement (Figure 5).

pharma classification pharma absorbance

Figure 4: Classification analysis                             Figure 5: Spectrum of each measurement

NIRS method generation: advantages of automation for raw material analysis

Visum Palm™ is the only NIR analyser on the market that allows end users to develop their own NIRS libraries or methods for identification, classification and quantification without the intermediary of technicians or specialists. Let’s see graphically below how existing multivariate data analysis – or also called chemometrics – software on the market for the development of NIRS methods and calibrations differs from IRIS Technology Solutions’ Visum Master™ software.

Identification et analyse des matières premières

Figure 6: (Left) Chemometrics software for method development and NIRS calibrations. (Right) Development of NIRS methods for identification, classification and quantification with Visum Master™ software.

The above is a graphical example to quickly differentiate how Visum Master™ simplifies a large number of scientific and technological tasks that until now had to be performed by chemometrics experts or specialists during the development phase of a NIRS method. Moreover, this software makes it accessible to any analyst to autonomously perform these tasks and edit the created methods when necessary, making the Visum Palm™ NIR analyser an open system that can cover different analytical needs with the appropriate training by the user, thus radically changing the accessibility and usability of the NIR technique.

The Visum Master™ software automatically generates a large number of successive predictive models by applying each time a certain combination of pre-treatments, algorithms and parameterisations. In all cases, it chooses the one with the lowest RMSE and risk of overfitting. It also automatically runs a spectral quality test to identify and remove spectral outliers, i.e. those spectra considered outliers in relation to a predefined range of variation for each class or value, and automatically produces a report of the developed NIRS method with all the information on how the model was generated, a document especially useful for the external validation of a quantitative NIRS method for release.

Development and edition of an identification or classification library for raw material analysis

To generate a library or identification method for raw material analysis (analogue for classification and quantification), it is only necessary to import the acquired spectra of each substance or calibration sample and enter its reference value, name or class. At the end of the data upload, Visum Master™ will generate the library automatically.

It is also possible to edit and iteratively strengthen the library to incorporate new substances or sample spectra from a new supplier. For each edition, a new version (v1, v2, …) is generated as a backup copy of the changes made. At the end of the process, the NIRS library or methods are exported to the Visum Palm™ portable analyser for use in the routine raw material analysis.

vms identification model

Figure 7: Development of a NIRS identification or classification method or library.

Conclusions

Raw material analysis, identification and qualification is an essential step in any GMP environment and, unlike other technologies, the NIR technique can identify and classify materials or substances or quantify different analytes of interest, thus reducing the workload in the laboratory or in the raw material receiving warehouse.

Visum Palm™ offers a unique value unlike any other device on the market in that the creation or editing of NIRS libraries and methods is automated and can be performed without specific spectroscopy knowledge, although it has an “Expert Mode” for advanced users that allows the choice of preprocessing and algorithms during the method generation phase that is activated by license. It also has the differential of offering automated reports that facilitate the work of any analyst in front of potential auditors in terms of external validation of the NIRS method, even for release.

Visum Palm™ has the following advantages:

  • It is useful for the identification and qualification of materials, including fluorescent materials, which cannot be analyzed by Raman spectroscopy.
  • It is a self-contained analyzer with embedded computer and touch screen.
  • It has a spectral resolution of 3 nm or 256 pixels and a measuring area of 10 mm in diameter.
  • It is also capable of automatically generating NIRS libraries or methods and downloading reports for each of them. The Visum Master™ software in its GMP version also allows the possibility to generate the operational qualifications of the device through a guided wizard and an Audit Trail report with all the information about the use of the device in compliance with 21 CFR Part 11.
Di IRIS Technology Solutions