IRIS Technology: Leading the Way in Material Detection with Hyperspectral Imaging for RECLAIM project

Innovation-pl, Pharma-4-0-pl 24 kwietnia 2025

Analiza surowców: identyfikacja (RMID), weryfikacja i klasyfikacja

Analiza surowców z Visum Palm GxP™

Analiza surowców poprzez identyfikację (RMID) jest kluczowym procesem w przemyśle farmaceutycznym, ponieważ zapewnia tożsamość i jakość wszystkich materiałów i substancji wykorzystywanych w procesie produkcji.
Praktycznym i efektywnym sposobem na przeprowadzanie analizy surowców i potwierdzenie tożsamości wszystkich substancji jest użycie przenośnego analizatora NIR Visum Palm GxP™.
Umożliwia on wykonanie analizy surowców bezpośrednio w magazynie, z uzyskaniem wyników w mniej niż trzy sekundy, zmniejszając tym samym obciążenie laboratoriów i skracając czas cyklu produkcyjnego.

Żadna pojedyncza technologia nie jest w stanie zapewnić uniwersalnego rozwiązania dla wszystkich materiałów używanych przez producenta.
Technologia NIR jest szczególnie skuteczna w identyfikacji związków organicznych, ale może być także stosowana do pewnych substancji nieorganicznych, zwłaszcza tych higroskopijnych, zawierających wodę (hydraty) lub rozpuszczonych w roztworze wodnym.

Z kolei spektroskopia Ramana ma pewne ograniczenia:

Związki organiczne wykazujące fluorescencję (takie jak barwniki czy niektóre API).
Substancje o bardzo słabych sygnałach Ramana.
Czyste związki jonowe, takie jak NaCl, KCl czy HCl.

analiza ilościowa postaci farmaceutycznych

análisis de materias primas con visum palm gxp

Dlaczego Visum Palm GxP™ do analizy surowców?

Jest to samodzielne urządzenie, które nie wymaga połączenia z żadnym urządzeniem zewnętrznym (smartfonem, tabletem ani komputerem).
Działa jako urządzenie ręczne oraz stacjonarne.
Jest przydatne zarówno do identyfikacji, jak i do opracowywania metod ilościowych w analizie surowców.
Obszar pomiaru próbki wynosi 10 mm, a obszar oświetlenia 50 mm, co umożliwia uzyskanie większej ilości informacji chemicznych i zmniejszenie niejednorodności próbek.
Oferuje rozdzielczość spektralną 5 nm i 256 pikseli, zapewniając najwyższą jakość wśród przenośnych analizatorów.

handheld nir analyzer BENCHTOP MODE AND BRIGHT RENDER

^{Rysunek 1:}^{Tryb stołowy z Visum Palm GxP™ umożliwia zamocowanie uchwytów próbek do proszków, substancji stałych i cieczy.}

Pełna zgodność z wymaganiami CFR i GMP:

Zdefiniowane role użytkowników: Analityk, Supervisor i Menedżer Użytkowników, z możliwością nieograniczonej liczby użytkowników.
Ustawienia wygaśnięcia haseł zgodnie z polityką bezpieczeństwa.
Rejestry Audit Trail przechowywane w zaszyfrowanych plikach binarnych, wraz z historią wyników.
Dwupoziomowy system podpisu elektronicznego (Analityk i Supervisor).
Ustawienia daty i godziny zgodne z wymogami CFR.
Bezpieczne procedury tworzenia kopii zapasowych i przywracania systemu.
Protokoły IQ i OQ zgodne z USP <1119>, PE 2.2.40, GMP i GAMP 5.

Tryby analizy w Visum Palm GxP™

Visum Palm GxP™ umożliwia szybką identyfikację lub weryfikację różnych substancji stałych, granulowanych, sproszkowanych i ciekłych.
Porównuje zmierzony widmo próbki ze wzorcowymi widmami zapisanymi w bibliotece urządzenia.
Porównanie opiera się na matematycznym indeksie podobieństwa (HQI).

W wyniku analizy surowców urządzenie podaje najbardziej podobną klasę lub substancję (patrz Rysunek 3), a następnie listę kolejnych potencjalnych dopasowań uporządkowanych według stopnia podobieństwa.

W przeciwieństwie do klasycznej identyfikacji, tryb weryfikacji (patrz Rysunek 4) pozwala analitykowi wybrać konkretną substancję z biblioteki, aby potwierdzić jej tożsamość.
Wynik analizy to PASS lub FAIL. W przypadku FAIL system zaproponuje także najbardziej podobną wykrytą substancję.

Główne ekrany Visum Palm™

^{Rysunek 2:}^{Menu główne} ^{Rysunek 3:}^{Analiza identyfikacyjna} ^{Rysunek 4:}^{Analiza weryfikacyjna, wynik pozytywny i negatywny wraz z potwierdzeniem poprawności substancji.}

Analiza klasyfikacji – Analiza surowców

W odróżnieniu od prostego potwierdzenia tożsamości, analiza klasyfikacji surowców (Rysunek 5) pozwala na dokładne rozróżnienie subtelnych różnic spektralnych, takich jak wielkość cząstek lub stężenie analitu, nawet w przypadku tej samej substancji czynnej (API) lub substancji pomocniczej.
Jest to bardzo przydatne narzędzie do wykrywania anomalii w analizie surowców lub do potwierdzania wyników w wątpliwych przypadkach.

Podczas każdej analizy surowców zapisywane jest również spektrum analizowanej substancji (Rysunek 6).

^{Rysunek 5:}^{Klasyfikacja analizy surowców}^{Rysunek 6:}^{Widmo każdego pomiaru}

Tworzenie własnych bibliotek za pomocą oprogramowania Visum Master™ – Analiza surowców

^{Rysunek 7: Visum Master™ – menu główne Rysunek 8: Visum Master™ – stworzenie od podstaw biblioteki lub metody analizy surowców}

^{Rysunek 9:}^{Wstaw widma i odniesienie, aby utworzyć model.}

Visum Palm GxP™ to jedyny przenośny analizator NIR na rynku, który pozwala użytkownikom końcowym na łatwe i automatyczne tworzenie własnych bibliotek do analizy surowców, klasyfikacji, a nawet testów ilościowych – bez potrzeby korzystania ze skomplikowanego oprogramowania czy zaawansowanej wiedzy chemometrycznej.

Wystarczy zaimportować widma próbek szkoleniowych oraz ich wartości referencyjne.
Oprogramowanie automatycznie generuje bibliotekę lub metodę oraz przygotowuje raport techniczny zawierający wszystkie szczegóły budowy modelu i główne wskaźniki jakości.

Raport ten spełnia wymagania wytycznych ICH Q2(R2) “Validation of Analytical Procedures – Scientific Guideline”, i nadaje się zarówno do walidacji wewnętrznej, jak i zewnętrznej.

IRIS Technology Solutions

Digitalization-pl, Industry-4-0-pl, Pharma-4-0-pl3 kwietnia 2024

Control of the coating process of granular forms by NIR spectroscopy

Digitalization-pl, Industry-4-0-pl, Pharma-4-0-pl3 kwietnia 2024

Control of the coating process of granular forms by NIR spectroscopy

Innovation-pl4 grudnia 2024

Monitorowanie Wolnego Laktydu podczas produkcji PLA (kwasu mlekowego)

Innovation-pl4 grudnia 2024

Monitorowanie Wolnego Laktydu podczas produkcji PLA (kwasu mlekowego)

Industry-4-0-pl5 kwietnia 2023

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

Industry-4-0-pl5 kwietnia 2023

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

European Commission Highlights IRIS Technology Solutions for its Innovative Role in the AIDPATH Decentralized Advanced Therapy Production Project

Control of the coating process of granular forms by NIR spectroscopy

Pharma-4-0-pl 9 kwietnia 2024

Blending process monitoring with in-line NIR spectroscopy

Real-Time blending process monitoring with NIR spectroscopy

Powders blending process is the most popular to achieve content uniformity in solid forms. Despite its apparent simplicity, i.e., taking advantage of shear forces for mixing APIs and excipients by merely moving the container for a certain time, any specialist in galenic does know that the real behavior of the mixture is not that simple. In fact, the final distribution results from a chaotic combination of microscopic interactions among the particles and macroscopic flow mechanics, not to mention that, once the homogeneity has been achieved, there is a real risk of demixing as a consequence of the affinity among homologous particles. That is why, regardless of the mechanical improvements in the blender’s design, systematically checking for mixture homogeneity is a key requirement in the pharmaceutical and nutraceutical sector. This is where NIR becomes important as a technique for real-time blending process monitoring.

Traditional control of the blending process vs. Blending process monitoring (PAT)

Up to now, periodically stopping the blending process after several cycles in order to take some samples from different points, which are further analysed by chromatography, has been the traditional way to do it. However, such an approach has also certain unwanted drawbacks, namely added lead time (due to the involved cumbersome lab procedures), suboptimal blending time (because of arbitrary extended blending intended for guaranteeing homogeneity) and blending artifacts (such as demixing and lumps as a consequence of keeping the load in static conditions while waiting for the lab results).

On the contrary, a PAT approach, such as a spectroscopy-based real time blending process monitoring, could be deemed the optimal way to check if the endpoint condition has been reached. In fact, both FDA and EMA have described such an approach as a recommended new paradigm.

In principle, as thoroughly described in the scientific literature, there are two ways for implementing a PAT-based endpoint determination: by using a supervised machine learning predictive model (for example, a PLS model that quantitatively predicts the API concentration) or by using an algorithm agnostic to the specific composition of the mixture. The first one usually renders more direct and accurate results but, in turn, it requires developing specific models on the basis of suitable reference samples, which is not always feasible, especially when there are too many different formulations. The agnostic approach for blending process monitoring, on the contrary, is based on spectral similarity; no ground truth data on the specific composition of each formulation is required in advance.

The agnostic approach: Moving-block Standard Deviation and the dynamic algorithm by IRIS Technology Solutions

Spectral stability is, in fact, agnostic to the specific composition of each formulation. No quantitative predictive model has to be developed for assessing the components concentrations because the underlying rationale states that, regardless of the composition, no improvement in homogeneity can be made once the spectra remain unchanged, at least for the major components. Indeed, a mixture can be deemed homogeneous once their spectra remain unchanged after several blending cycles.

Since the NIR spectroscopy is sensitive to 0.1-1 % or higher concentrations, during during blending process monitoring the homogeneity of minor components cannot be assessed by means of such a technology. However, it can be inferred from the homogeneity of major components and opportunely validated with traditional lab methods if required.

Moving-block Standard Deviation (MBSD) is the most widely described agnostic algorithm, at least in the scientific literature. Usually, the MBSD endpoint criterion is rather arbitrary. Even when a statistically-founded criterion is used [Critical evaluation of methods for end-point determination in pharmaceutical blending processes. M. Blanco, R. Cueva-Mestanza and J. Cruz. Anal. Methods, 2012, 4, 2694], some restrictive hypothesis on the distribution of the similarity metric should be fulfilled in order to be properly applicable. Moreover, the mean of the standard deviation has a rather “smoothing” effect that could veil to some extent the real trend of the spectral similarity.

The dynamic approach with Visum NIR In-Line™ for blending process monitoring

IRIS Technology Solutions’ proprietary algorithm, on the contrary, is based on checking for the stability of a true similarity metric (MSD: mean squared difference between two successive spectra) by using strong statistical criteria on the blending-specific MSD distribution. In fact, our moving block approach dynamically adapts the threshold to each formulation-wise spectral-similarity statistical distribution. Consequently, it provides a robust endpoint criterion for blending process monitoring regardless of the specific behavior of each formulation, which is particularly required when mixing anomalies such as demixing or lumps formation take place.

For the sake of flexibility, the users can set both the moving block size and the statistical significance at their convenience. Whenever possible, such parameters should be tuned in the commissioning stage although the factory-set values should work for the most frequent circumstances.

^{Image 1: Sapphire window adapter module for Visum NIR In-Line analyser ™ manufactured by IRIS Technology Solutions S.L.}

The adapter module with sapphire window allows easy integration of the Visum NIR In-Line™ analyser via a tri clamp connection. There are different sizes of the adapter module depending on the blending machine’s own configurations.

Unlike other analysers on the market, the Visum NIR In-Line™ is a self-contained analyser (embedded computer) and can communicate with multiple communication protocols. It also complies with the pharmaceutical regulation 21 CFR Part 11 (FDA), the requirements of the American (USP) and European (Ph. Eur.) Pharmacopoeia and the European Medicines Agency (EMA) Guidelines 2014 and 2023.

In its Blender version, the Visum NIR In-Line™ analyser is wireless, powered by rechargeable and replaceable batteries with a battery life of more than 3 hours and connected via Wi-Fi, as shown in the image below.

_{Image 2: Visum NIR In-Line™ analyser in a blending process monitoring cycle.}

_{Table 1: Visum NIR In-Line analyser ™ technical specifications}

Conclusions

The IRIS Technology Solutions S.L. In-Line™ NIR analyser presents a more robust and realistic dynamic method for blending process monitoring than the Moving-block Standard Deviation (MBSD) algorithm in that it is based on the quadratic mean of two successive spectra and not on the average of the standard deviation as a similarity index used by the MBSD approach.

As it has an embedded computer, it does not need to be connected to other electronic devices or external computers, making it an excellent stand-alone tool for working at the plant production level and in GMP environments.

In addition, it has a much larger illumination and spectrum acquisition area than other NIR analysers, especially those very small ones, with a resolution of 256 pixels, obtaining more chemical information and spectral quality for optimal monitoring of each blending cycle.

IRIS Technology Solutions

Blending process monitoring with in-line NIR spectroscopy

Real-time NIR grain analysis

Digitalization-pl, Industry-4-0-pl, Pharma-4-0-pl 3 kwietnia 2024

Control of the coating process of granular forms by NIR spectroscopy

In the pharmaceutical industry, there are many granular formulations that are coated to achieve a sustained or controlled release of the drug or active pharmaceutical ingredient (API) over time, a clear and well-known example being Omeprazole. In this paper we will discuss these extended release formulations and how it is possible to optimize the release time and potency analyses during the coating process using NIR spectroscopy.

Pelletisation process and traditional analysis

During the pelletisation process of modified release dosage forms, the correct application of the coating (e.g. an enteric release coating intended to prevent gastric digestion or degradation) will determine the subsequent efficacy of the drug and the mg/API release time of the drug and therefore controls are carried out throughout this process to ensure the quality and thus the expected pharmacological action.

Currently, this control is performed during the coating process with samples obtained from the coating equipment at different times and analysed in the laboratory using the analytical technique of HPLC or liquid chromatography and dissolution testing to demonstrate that the release of the active ingredient(s) is satisfactory. Both methods require sample preparation prior to analysis, require specialised personnel and consumables (materials), in addition to the duration (hours) of a dissolution test, whose main objective is to determine the bioavailability of the drug, meaning the relative amount of the drug that has entered the general circulation after administration, and the rate at which this access has occurred.

Therefore, the major problem with traditional analytics is that it is time-consuming to obtain the results and therefore does not allow for timely rectification of the coating process in case of failures or, in the frequent case of stopping the process for sampling, there is a risk that the quality of the semi-product will be altered.

An alternative and very effective tool that allows real-time monitoring of the coating process is NIR technology, since the spectral signature of each pellet can be related to its coating conditions, dosage and release times without the need to resort to traditional methods.

Development of an NIRS method for predicting release time and potency

In order to develop a predictive model for the real-time determination of release times and potency (mg API/g pellet) that is released at 1, 4 and 7 hours, we worked in coordination with a major Spanish pharmaceutical laboratory and the portable NIR spectroscopic analyser Visum Palm™ manufactured and marketed by IRIS Technology Solutions S.L.

The data provided by the laboratory consists of the NIR spectra of several batches of two drugs based on, on the one hand, an antihistamine which, for confidentiality reasons, we will refer to as „DS”, and on the other hand, a form of vitamin B6 which, for the same reasons, we will refer to as „PH”. In both cases, the active substance was part of the coating of the pellets constituting the vehicle.

The spectra of the pellets were acquired at different times of the coating process, from both wet and dry samples and, in parallel, the respective sample was subjected to the usual analyses in these cases to determine the drug release at 1, 4 and 7 hours and the potency mg PI/g.

The predictive models developed on the basis of the spectral data showed that it is not necessary to dry the samples for the acquisition of the spectra – so the control can be performed directly on the wet sample, saving time and handling – and that there is a clear relationship between the NIR spectra, the power and the release times of 1h, 4h and 7h, as we will see below.

PH compound - Coating process and NIR spectroscopy

^{Table 1: Quality parameters of the prediction models for the release at 1, 4, 7 hours and the potency in the samples with different stages of the PH coating process. The * symbol indicates that the model was built by using the average NIR spectra of the replicates of each sample.}

^{Figure 1: Regression curves for PH a) All samples; b) Batches 1,3,4 y 7; c) Mean spectra of batches 1,3,4 y 7; d) Batch 7.}

DS compound

^{Table 2 shows the quality parameters of the models for the analysis of wet DS samples. All samples were studied simultaneously: samples from batches 6, 8 and 10 together, and batch 6 separately. Batches 6, 8 and 10 were chosen for the study of a set of batches because they had the largest number of samples. In addition, batch 6 was chosen for individual analysis as it contained the most samples with the optimal release parameters for the case study.}

^{Table 2: Quality parameters of the prediction models for the release at 1, 4, 7 hours and the potency in the samples with different stages of the DS coating process.}

Figure 2 shows the regression curves resulting from the study for the active substance DS. The values of the quality parameters for the DS models show, in general, a good correlation. As an observation, it is noted that the error increases when data from different batches are used, probably because the process conditions of each batch are different due to the fact that the data come from the development and fine-tuning phase of the production process. The prediction of the release at 7 hours is worse than that of the other parameters, probably because the end of the release process has been reached in many cases before that time.

_{Figure 2: Regression curves for DS a) all samples; b) Batches 6, 8 y 10; c) Mean spectra of batches 6, 8 y 10; d) Batch 6.}

Prediction of dry samples

^{Table 3: Quality parameters of the prediction models for the dry samples of DS batch 6 and PH batch 7.}

The prediction models of the dry samples for individual batches of PH and DS show a good correlation. It should be noted that the prediction error is due to the few validation samples used.

^{Figure 3: Regression curves for Dry simples of a) DS batch 6 y b) PH batch 7.}

Conclusions - Coating process and NIR spectroscopy

There is a clear correlation between NIR spectra with release times of 1h, 4h and 7h, as well as with potency, for both DS and PH, although it is slightly worse for PH.
In the case of the 7h release, the correlation seems a bit weaker, possibly because it is close to the maximum release (at the release plateau) or due to differences in the pH of the samples.
The different batch production conditions affect the robustness of this correlation, an inherent variability factor because the samples come from the development phase of the production process (fine-tuning phase) and not from the NIRS method.
Individual batch tests show a good correlation for both wet and dry samples. Since the results in both cases are similar, it can be concluded that drying is not necessary to correlate the studied parameters (release time and potency) with the NIR spectra.
Finally, from the analysis of the results analysed, it can be concluded that NIR spectroscopy can be used to optimise the control of the coating process of granular forms and that, from a technical point of view, it is a robust and evidence-based method. However, for all the cases evaluated in this document, definitive models have to be made once the production process has been fully developed.

IRIS Technology Solutions

Plastic identification, verification and classification using Visum Palm™

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

Ai-pl, Digitalization-pl, Industry-4-0-pl, Innovation-pl, Pharma-4-0-pl 5 września 2023

New Visum Palm™ AI-assisted handheld NIR analyser

IRIS Technology Solutions introduces the latest version of its Visum Palm™ portable NIR analyser to complement its Visum® range of real-time process analysers for industry.

The new Visum Palm™ is a fully portable NIR spectrophotometer that allows real-time analysis of different substances, products or mixtures, without the need for traditional laboratory and sampling techniques, allowing industry to obtain results on the spot to make decisions or correct production process parameters.

The new generation Visum Palm™ brings with it an innovative design and a radical change in the way users experience NIR technology, now assisted by AI with the Visum Master™ software, so that each manufacturer can automatically create their own predictive models or calibrations according to their control and analysis needs.

Design, autonomy and robustness

The Visum Palm™ handheld nir analyser offers an innovative and ergonomic design, as well as the possibility to perform analysis at any time and place without having to connect it to any external electronic device. This is possible because it incorporates an embedded touch screen and computer, which enable all the routine functionalities of the device.

The Visum Palm™ operates in the 900 to 1700 nm range, as this is the band that best combines availability of chemical information with price and technological maturity. It operates mainly in diffuse reflectance mode, for which it has specially designed and patented optics to extract as much information as possible from the sample. Specifically, it has a large illumination area (50 mm diameter) and a collection area of 10 mm. These features differentiate it from similar analysers in terms of its suitability for analysing heterogeneous samples, which is most often the case in real working conditions. In cases where heterogeneity is more evident, the device is configurable to calculate and report the average of a given number of repetitions.

The Visum Palm™ handheld NIR analyser is IP65 compliant, making it resistant to dust, moisture and water. It is also rugged enough to be carried and tested almost anywhere indoors or outdoors and even comes with a stand for desktop or tabletop use.

A new AI-assisted user experience

Unlike most common modelling and calibration software on the market, which requires the user to have some technical knowledge of chemometrics or entrust the task to a third party, Visum Master™ PC-based software makes NIR technology even more accessible by automating pre-processing, multivariate analysis algorithm selection and validation. This allows any user to generate models by simply inputting spectra and references (quantitative or qualitative) for routine real-time analysis to replace traditional analysis.

The new software also allows to extend and edit pre-existing models, synchronise with the portable analyser to import spectra, export models, download measurement results, automatically generate analytical method validation reports and audit reports for GMP environments, and to check the metrological performance of the device in a guided manner when needed.

For industry and GMP environments

While NIR technology has a myriad of applications in numerous industries such as plastics, food, chemical, agribusiness, wood, biofuels, to mention the most relevant but not the only ones; it is for the pharmaceutical industry and GMP environments where the new Visum Palm™ device introduces significant novelties at the level of usability and functionality. It is 21 CFR Part 11 compliant, allowing the generation and display of an automatic Audit Trail report, the record of all device activity, where comments and observations can be incorporated. It also allows the user to automatically generate the analytical method validations developed and perform metrological checks of the device when required and download the results at a later date.

„NIR technology today must be easy to use and understand, and at the same time it must give the user the freedom and autonomy to exploit it to the full and facilitate their day-to-day work. Technology must be an enabler. We will continue to take further steps in terms of automation and new functionalities because we are convinced that this is the right way forward and what the industry and the people in it need”, says Oonagh Mc Nerney, Director of IRIS Technology Solutions, S.L.

The new Visum Palm™ handheld NIR analyser is now available here, where you can also find technical information about the device, videos and contact IRIS Technology Solutions, S.L. for a demonstration or specific enquiry.

IRIS Technology Solutions

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