Blending process monitoring with in-line NIR spectroscopy

What is the best handheld NIR analyzer on the market? A comparison between Visum Palm™ and other portable NIR devices

Pharma-4-0 22 September 2025

Visum Palm GxP: The New NIR Analyzer for Pharmaceutical

handheld-nir-analyzer-for-pharmaceuticals

Visum Palm GxP: The New NIR Analyzer for Pharmaceutical

The Visum Palm GxP is the latest NIR analyzer for pharmaceutical applications developed by IRIS Technology Solutions. This portable, robust, and fully validated device redefines how the pharmaceutical industry performs quality control, batch release, and raw material verification, delivering speed, precision, and regulatory compliance in one instrument.

With a spectral range of 900 to 1700 nm and a signal-to-noise ratio of 4500:1, the Visum Palm GxP ensures reliable results in every measurement. Its self-contained architecture and embedded software make it the ideal tool for GMP environments, whether in the laboratory, production area, or warehouse.

Why Choose a NIR Analyzer for Pharmaceutical Applications

Near-Infrared (NIR) spectroscopy has become a cornerstone technology for the pharmaceutical industry. It enables non-destructive sample analysis, requires no preparation, and delivers results in seconds. A NIR analyzer for pharmaceutical processes provides clear advantages:

Rapid identification of raw materials, even through transparent packaging.
Real-time, in-line process control.
Evaluation of content uniformity and moisture (loss-on-drying).
Faster batch release, reducing QC lead times.

The Visum Palm GxP takes these benefits further by combining premium hardware with advanced software tools, meeting the most demanding requirements of international regulations.

Key Features of the Visum Palm GxP: Technical Specifications

Developed specifically as a NIR analyzer for pharmaceutical use, the Visum Palm GxP complies with 21 CFR Part 11, USP <1119>, Ph. Eur. <2.2.40>, and GAMP 5 standards. Notable specifications include:

Spectral range: 900–1700 nm
Design: self-contained analyzer (built-in computer, software and touchscreen), eliminating the need for an external PC, tablet, or mobile device. This simplifies daily operation and qualification process in GMP environments.
Spectral resolution: 5 nm with 256 channels — the highest resolution available among portable NIR analyzers.
Signal-to-noise ratio: 4500:1 (almost twice the USP <1119> standard).
Measurement area: 10 mm with 50 mm illumination.
Measurement time: 3 seconds.
Geometry: diffuse reflectance; transflectance with optional accessory.
Weight: 1.8 kg, IP54–IP66 protection.
Battery life: up to 5 hours, rechargeable and replaceable.

These features guarantee analytical reliability, even under demanding production conditions.

Regulatory Compliance and Data Security

The Visum Palm GxP is designed to be the most comprehensive portable NIR analyzer for pharmaceutical environments, offering advanced functionality for GMP compliance, particularly with FDA 21 CFR Part 11:

Full audit trail with complete traceability of operations and results (who did what and when). Includes a device audit trail and a results-only audit trail.
Daily instrument diagnostics with alarms for operating status.
Role-based access control (Analyst, Supervisor, User Manager) with privileges preconfigured by the manufacturer.
Electronic signatures with dual authentication (Analyst and Supervisor).
Secure password policies, automatic session logout, and recovery functions.
Safe backup and restoration of data.

These capabilities guarantee data integrity and simplify regulatory audits.

Visum Master™ GMP Software: Intelligence Applied to NIR

A critical component of the NIR analyzer for pharmaceutical Visum Palm GxP is its software ecosystem:

Visum Master™ GMP enables the creation of identification libraries and quantitative models without advanced chemometrics expertise. It is the only software on the market that automates NIR library development thanks to its built-in Model Builder.
Automatically generates complete reports compliant with ICH Q2(R2), supporting both internal and external validations.
Includes automatic diagnostics, user management, and tools for wavelength accuracy, noise, and photometric linearity verification according to USP, Ph. Eur., and JP18.

As a Class 4 software package, Visum Master™ simplifies qualification tasks, making the deployment of a NIR analyzer for pharmaceutical operations faster and more efficient.

Accessories to Expand the Potential of the NIR Analyzer for Pharmaceutical Use

The Visum Palm GxP comes with a full range of accessories designed for laboratory and production needs:

Benchtop sample holders for solids, granules, and powders.
Cuvette holders (1–10 mm) for liquid analysis in transflectance mode, compatible with disposable or reusable cuvettes, open or sealed.
Mini sampler and surface flattener.
Optional barcode reader for streamlined traceability.

These accessories enable the NIR analyzer for pharmaceutical applications to handle diverse sample formats — from fine powders to liquids or granules — and to switch seamlessly between handheld and benchtop configurations.

Use Cases for the NIR Analyzer for Pharmaceutical Visum Palm GxP

The NIR analyzer for pharmaceutical Visum Palm GxP offers a wide range of applications across the industry, from raw material reception to final batch release. Its portability, validated software, and exceptional signal-to-noise ratio make it indispensable for meeting GMP standards and streamlining workflows. Let’s see the most relevant nearinfrared spectroscopy applications in pharmaceuticals and life sciences industries:

Raw Material Identification

The Visum Palm GxP allows operators to identify and verify active ingredients and excipients in seconds, even without opening translucent or transparent packaging. This reduces QC time, minimizes cross-contamination risk, and lowers human error during incoming inspections.

NIR technology is particularly effective for organic raw materials, and it can also verify inorganic substances when hydrated, hygroscopic, or in solution. Compared to other techniques, a NIR analyzer for pharmaceutical use is faster, more economical, and safer than handheld Raman analyzers, which struggle with pure ionic compounds (NaCl, KCl, HCl) or substances that fluoresce.

The Visum Palm GxP simplifies the development of robust identification libraries, accommodating variations between suppliers and batches while ensuring full traceability and compliance with pharmacopeias like USP and Ph. Eur. As a result, the NIR analyzer for pharmaceutical becomes the first line of defense for supply chain integrity.

Content Uniformity and Quantification

With its high signal-to-noise ratio (4500:1) and 5 nm resolution, the Visum Palm GxP is an ideal NIR analyzer for pharmaceutical quantification. It supports the development of automated quantitative models to assess content uniformity in tablets, capsules, granules, emulsions, liquids, or powder blends, as well as the exact concentration of APIs and excipients.

The NIR analyzer for pharmaceutical allows automated model training and provides advanced tools and metrics for evaluating result quality, even offline with validation spectra. Automatic reporting follows the guidelines of ICH Q2(R2) – Validation of Analytical Procedures, reducing the time and effort required for method documentation.

Real-Time Process Control

As a NIR analyzer for pharmaceutical manufacturing, the Visum Palm GxP can be installed at critical production points or used in the lab to monitor essential variables:

Residual moisture in granules or powders during drying.
Drying progress in fluid beds.
Coating thickness on microgranules or tablets.
Blend uniformity before compression or encapsulation.

Information provided by the NIR analyzer for pharmaceutical enables near real-time process adjustments, improving product quality and reducing the risk of out-of-specification batches. This Process Analytical Technology (PAT) approach strengthens statistical process control and supports more robust manufacturing.

Batch Release

The Visum Palm GxP accelerates batch release thanks to its fast, non-destructive analysis. By delivering analytical results in seconds without compromising product integrity, the NIR analyzer for pharmaceutical enables immediate decisions on batch acceptance or rejection. This shortens QC cycles and enhances overall plant efficiency.

Because it is portable, the NIR analyzer for pharmaceutical can analyze batches in storage, on packaging lines, or in the lab, adapting to any scenario without sacrificing reliability or regulatory compliance.

Research and Development

Beyond routine QC, the Visum Palm GxP is an excellent NIR analyzer for pharmaceutical R&D environments. It supports excipient compatibility studies, formulation optimization, and stability testing, providing fast insights into the behavior of new products while consuming minimal material. This makes it ideal for pilot projects and scaling new dosage forms.

Advantages over Other Portable NIR Analyzers

Unlike generic devices, the Visum Palm GxP is designed exclusively as a NIR analyzer for pharmaceutical workflows. Its key advantages include:

Built-in validation and regulatory compliance, facilitating qualifications and validations from the start.
Optimal performance in GMP environments, with complete auditing and traceability.
Rugged hardware, ideal for warehouses, production areas, or laboratories.
Dual functionality: handheld and benchtop operation in one instrument.
Intuitive software for model building, library management, and data control.

These qualities make the Visum Palm GxP the safest choice for organizations seeking a NIR analyzer for pharmaceutical tasks with full support.

Conclusion

The Visum Palm GxP is far more than just a NIR analyzer for pharmaceutical testing. It is an integrated solution for quality control, raw material identification, and process optimization in GMP environments. Its portable, self-contained design, dual functionality, high performance, and regulatory compliance position it as the ultimate tool for laboratories and manufacturing plants seeking speed, reliability, and security in their operations.

If your company aims to enhance efficiency and compliance in NIR analysis, the Visum Palm GxP is the definitive NIR analyzer for pharmaceutical choice.

By IRIS Technology Solutions

Raman Spectroscopy in Liposome Diafiltration Process

The pharmaceutical industry frequently relies on the encapsulation of active pharmaceutical ingredients (APIs) in liposomal systems to improve their stability, bioavailability, and controlled release. A key step in this process is diafiltration, which removes unwanted compounds after liposome formation, including organic solvents like ethanol, which is used to dissolve the lipids that form the liposomal bilayer. Accurate quantification of residual ethanol using Raman spectroscopy-based analyzers is essential to ensure the final product quality, meet regulatory standards, and optimize process time and resources.

Raman Spectroscopy and the Visum Raman In-Line™ System

Raman spectroscopy is a vibrational technique based on the inelastic scattering of laser light. It is highly specific for each molecule, making it ideal for the identification and quantification of chemical components, even in complex matrices. The Visum Raman In-Line™ system, developed by IRIS Technology Solutions, allows the application of Raman spectroscopy directly in industrial or laboratory settings thanks to its compact, robust, and adaptable design. It eliminates the need for sample preparation, enables fast, real-time analysis, and is ideal for continuous monitoring of pharmaceutical processes with high regulatory demands.

Quantification of Residual Ethanol by Raman Spectroscopy

This project focused on implementing a residual ethanol quantification model using Raman spectroscopy during the diafiltration process following liposome formation. For confidentiality reasons, the two encapsulated active ingredients analyzed are referred to as 1: NSAID (non-steroidal anti-inflammatory drug) and 2: Biomolecule. Samples were analyzed under controlled laboratory conditions using the Visum Raman In-Line™ system. The Raman system was mounted on a mobile rack, with a sample holder adapted for Falcon-type vials, ensuring laser safety during operation.

Spectral analysis was complemented with data obtained through high-performance liquid chromatography (HPLC), the reference method used to determine the actual ethanol concentration in the samples. These data were used to train and validate the Raman spectroscopy predictive models. The target ethanol concentration in the final product was set below 0.1% v/v, and the training samples covered a full range from 0% to 10% v/v ethanol.

^{Image of In-Line™ Raman analyzer system mounted on a mobile rack.}

Development of the Predictive Model with Visum Master™

For developing the predictive model, synthetic samples were prepared in the laboratory by mixing water with varying ethanol concentrations, specifically designed to span the entire operational range expected in the real process. These samples ensured that the model could make accurate predictions across the entire interval of interest.

The Raman spectra obtained using the Visum Raman In-Line™ from these solutions were used to develop the predictive model with Visum Master™, an automated software platform that allows any user to create calibrations without needing advanced chemometric knowledge. The software automatically selected the most appropriate algorithm, optimal preprocessing methods (Savitzky-Golay derivatives, mean centering, baseline correction, etc.), and configured the final model using the calibration samples and their reference values (determined by HPLC).

The resulting models were later validated using an independent set of real samples collected during experimental liposome production.

Results and Evaluation of the Raman Predictive Model for Residual Ethanol

The models developed using Raman spectroscopy for quantifying active ingredients and residual compounds demonstrated excellent performance in both calibration and external validation. For ethanol, the model achieved a coefficient of determination (R²) above 0.99 for both calibration and validation, with a root mean square error of prediction (RMSEP) below 0.35% v/v, confirming its applicability for real-time monitoring during drying or cleaning processes.

The consistently low bias in all cases supports the robustness of the calibration and the absence of systematic errors, confirming the viability of Raman spectroscopy as a reliable technology for the quantitative monitoring of active ingredients in critical pharmaceutical processes.

Conclusions

The use of Raman spectroscopy through the industrial Visum Raman In-Line™ analyzer enabled the development of a robust and accurate model for ethanol monitoring during the diafiltration step in pharmaceutical processes. The high correlation and low deviation of results confirm the system’s suitability for real-world applications both in the laboratory—mounted on a mobile rack—and in in-line monitoring processes. Raman spectroscopy can also be extended to other pharmaceutical processes requiring precise control of solvents or critical compounds, enhancing operational efficiency and final product quality.

By IRIS Technology Solutions

Pharmaceutical Raw Material Identification (RMID) with Visum Palm GxP™

Raw material identification or verification analysis is a critical process in the pharmaceutical industry, as it ensures the identity and quality of all materials that will be used in production. A practical and efficient way to perform it is through the Visum Palm GxP™ portable NIR analyzer, which allows the test to be carried out directly in the warehouse and provides accurate results in less than 3 seconds, avoiding laboratory overload and reducing production cycle times.

There are multiple technologies commonly used for raw material identification (NIR, FT-NIR or Raman), but none of them alone constitutes a universal solution that covers the entire list of materials of a pharmaceutical manufacturer.

NIR technology is especially effective in the identification of organic compounds, although it can also be applied to certain inorganic materials under very specific conditions, such as in the case of hygroscopic substances (salts), hydrated compounds or those dissolved in aqueous solution.

On the other hand, Raman spectroscopy represents an alternative technique with its own limitations, especially in:

• Organic compounds with fluorescence (colorants and certain APIs).
• Substances with weak Raman signals.
• Purely ionic inorganic compounds (NaCl, KCl, HCl).

In general, NIR is widely established in regulated environments due to its effectiveness, immediacy and ease of use by any operator. In addition, it does not require additional safety measures (as in the case of Raman, where protective glasses are needed) and is a much more economical option for pharmaceutical raw material identification and quantitative analysis.

handheld nir visum palm analyzing pharmaceutical raw material

Doing some tests with the handheld nir visum palm

Why Visum Palm GxP™ for pharmaceutical raw material identification?

Visum Palm GxP is a self-contained analyzer that does not need to connect or link to any external device (smartphone, computer, tablet or other).

It has dual functionality, allowing its use both as a handheld portable device (in direct contact with the sample) and in benchtop mode. It offers a spectral resolution of 5 nm or 256 pixels, placing it as the portable NIR analyzer with the highest spectral capacity in its category.

It complies with the main international regulatory frameworks: CFR 21 Part 11, USP 1119, Ph. Eur. 2.2.40, JP18 and GAMP 5. As a standalone system with class 4 software, the pharmaceutical qualification procedure is much more agile and simple compared to other analyzers that depend on external software or additional processing units.

The measurement area is 10 mm in diameter, with an illumination area of 50 mm, which ensures greater chemical information and makes it an especially useful solution for raw material identification in large and translucent bags.

The system includes a set of accessories that allow working in benchtop mode or as a handheld analyzer, including adapters for laboratory spectrophotometry cuvettes and vials for liquids and powders. In addition, it has an optical reducer designed for tablet inspection and other reduced analysis areas.

Visum Palm GxP is not only optimized for pharmaceutical raw material identification, but also offers support for quantitative analysis. Automatically generated technical reports follow the guidelines of ICH Q2(R2) – Validation of Analytical Procedures – Scientific Guideline, ensuring traceability and regulatory compliance.

handheld nir analyzer BENCHTOP MODE AND BRIGHT RENDER

^{Figure 1: Support base for working in benchtop mode with Visum Palm GxP™. Allows coupling of benchtop sample holders for powders, solids, granules and liquids.}

GxP and CFR 21 Part 11 functionalities

Visum Palm GxP integrates the most complete and up-to-date set of functionalities specifically designed to guarantee raw material identification and regulatory compliance in pharmaceutical environments regulated by GMP. Its software and hardware architecture positions it as the reference tool to ensure quality, traceability and analytical reliability at every stage of the process.

Among its main features:

• Complete Audit Trail: detailed recording of both the device and the results, with encrypted binary files for maximum security.
• Advanced role and privilege management: three predefined levels (Analyst, Supervisor and User Manager) with the possibility of creating unlimited users.
• Secure access control: robust passwords with intuitive modification and restoration procedures.
• Configurable time parameters: session time and password expiration management.
• Flexible time synchronization: multiple methods to ensure accurate date and time on the device.
• Integrated qualification assistant: guided validation of wavelength accuracy, noise and photometric linearity.
• Dual-level electronic signature: with independent validation by Analyst and Supervisor.
• Backup and restoration procedures: designed to maintain system integrity and operational continuity.

Thanks to this set of functionalities, Visum Palm GxP is consolidated as the most robust portable analyzer on the market, ensuring not only compliance with international regulations (CFR 21 Part 11, GAMP 5, pharmacopeias), but also maximum efficiency in pharmaceutical raw material identification and quantitative analysis applications.

Analysis modes with Visum Palm GxP™ for raw material identification

The Visum Palm GxP™ analyzer enables raw material identification or verification analysis in less than 3 seconds for different compounds in solid, granular, powder or liquid state. The procedure consists of comparing the spectrum acquired from the sample with the reference spectra stored in the library.

The comparison is carried out through a mathematical similarity criterion (HQI, Hit Quality Index), which converts spectral differences into a numerical value. As a result, the device provides the substance or class with the highest degree of similarity obtained (Figure 3) and displays a list of the other substances ordered from highest to lowest match.

Likewise, the system allows a verification analysis, previously selecting from the library the specific material whose identity is to be confirmed. In this case, the result is presented as PASS or FAIL and, in case of FAIL, the analyzer also indicates the correct substance with the highest similarity (Figure 4).

All results, including discarded ones or those that have not been electronically signed by the user using credentials, are stored in the encrypted Audit Trail, ensuring traceability, data integrity and GMP regulatory compliance.

Main screens of Visum Palm™

Software main menu, Raw material identification analysis and Verification analysis, PASS and FAIL with confirmation of correct substance windows

^{Figure 2: Main Menu Figure 3: Raw material identification analysis Figure 4: Verification analysis, PASS and FAIL with confirmation of correct substance.}

In specific cases it may occur that the technology does not provide an exact result, as happens when inspecting chemically very similar or practically identical materials, or when there are differences in granulometry. For these situations, Visum Palm GxP™ offers the possibility of creating and using classification libraries.

Unlike identification/verification modes, classification (Figure 5) allows precise distinction of very subtle spectral differences, such as particle size or the concentration of a specific analyte, even when dealing with the same API or excipient present in different concentrations within similar matrices. In this way, classification complements the initial raw material identification analysis through a more powerful algorithm for complex or problematic cases.

In all the scenarios described, in addition to the result, the system generates the complete spectrum of the analyzed substance in each measurement (Figure 6), ensuring traceability and greater analytical value.

software classification analysis and Spectrum of each analysis windows

^{Figure 5: Classification analysis. Figure 6: Spectrum of each analysis.}

Develop raw material identification methods and libraries with Visum Master GMP™ software for PC

^{Figure 7: Visum Master™ – Main Menu Figure 8: Visum Master™ – Model Builder}

the spectra of each material and the reference to create the raw material identification library window

^{Figure 9: Insert the spectra of each material and the reference (name) to create the raw material identification library.}

Visum Palm GxP™ is the only NIR analyzer on the market that allows the end user to easily and fully automatically develop their own raw material identification libraries, classification libraries or even methods for quantitative tests, without the need to use complex software or have prior knowledge in chemometrics. In other words, the user only needs to have samples and qualitative or quantitative references, leaving the integrated Model Builder to handle the development process.

Generating, maintaining or updating libraries has never been as simple as with Visum Master™, since it allows generating unlimited libraries and methods for different types of analysis, and for each one it also automatically generates a technical report with all the information on how it was done, the algorithm used, pretreatments, latent variables, quality metrics, dataset used, outlier quality control, graph and quantification of detected and eliminated outliers, among other data that are a key input to prepare an internal or external validation report, identify improvement needs or updates.

To learn more about how Visum Palm GxP can be a useful tool for raw material identification, you can contact IRIS or our distributors through the following link.

By IRIS Technology Solutions

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.

By IRIS Technology Solutions

Control of the coating process of granular forms by NIR spectroscopy

monitoring of the pellet coating process

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.

By IRIS Technology Solutions

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.

By IRIS Technology Solutions

NIR technology and Raman spectroscopy: introduction and applications in the pharmaceutical industry

In the following article we will address the main applications with NIR technology and Raman spectroscopy, in real time, for the control of manufacturing and quality processes both for pilot plant – in tune with the Quality by Design (QbD) concept – and for industrial scale-up. In addition, this article is intended to be a starting point for industry professionals to raise questions about how to optimize control with process analytical technologies (PAT) for efficient management and implementation of a continuous manufacturing model.

Raman and NIR Spectroscopy

Both technologies have in common that they are photonic techniques – they take advantage of the properties of photons or light and their interaction with matter – diagnostic and non-destructive, allowing chemical and structural information to be obtained in seconds from almost any organic or inorganic material or compound. Hence, their use in laboratories is widespread in different industries and they are analytical techniques known by quality control professionals.

For those who are not laboratory professionals or are just entering the field, it is essential to start with a few brief concepts and examples to understand its applications.

Raman spectroscopy is a technique based on the inelastic scattering of light. Inelastic or Raman scattering occurs when the energy changes during the collision between the monochromatic light and the molecule and, therefore, the frequency of the scattered light also changes. These changes provide information about the molecular identity and structure of the samples or material being analyzed.

Near infrared spectroscopy (NIR) is a technique based on the interaction between electromagnetic radiation and matter, within the wavelength range of 780-2500 nm. These absorbed radiations can be related to different properties of the sample, providing qualitative and quantitative information. The near-infrared range is characterized by weak overtones and combined bands arising from the strong fundamental vibrations of O-H, C-H, C-O, C=O, C=O, N-H bonds and metal-OH groups in the mid-infrared range.

However, both Raman and NIR spectroscopy devices in real time are optical (vision) devices that work with artificial intelligence. The information they collect from the spectrum of the analyzed object is interpreted by a mathematical model – chemometrics – called a “predictive model” that tells the system what it is looking at. A very simple example: if we want to control the Paracetamol content of a 1mg. form, the mathematical model that analyzes the process must know how to correlate the spectrum corresponding to that value and for that it must know what is 0.8 – 0.9 – 1.1 and so on in the range of interest to be controlled. The predictive model is a mathematical model that essentially correlates a spectrum with a reference value. This reference value comes out of the traditional laboratory analysis.

Let’s get down to the important: What use are these systems in my factory?

Applications of real-time NIR technology:

1) Raw material identification: Identification of raw materials is a routine task in the pharmaceutical industry. These tests are carried out before the materials are processed, in order to avoid errors as much as possible and thus save time and money. This material testing applies not only to purchased materials (e.g. excipients), but also to some internal material transfers, e.g. APIs manufactured in another plant. The latter is very important to take into account when wondering why we have problems in mixing some formulations with certain raw materials.

2) Homogenization: Once identified and weighed, raw materials usually require homogenization of the different components. This is a critical step in the manufacture of solid-state pharmaceutical products, as it has a direct impact on the quality and homogeneity of the final product. The homogenization process is mainly affected by physical properties such as particle size, shape and density. Mixing endpoint and homogenization are not the same, not in terms of regulation according to the European Medicines Agency (EMA). From IRIS Technology we try to raise awareness on this point, which is sometimes confused, to provide in-line control solutions that are homologous to the control protocols established by the EU and Spanish regulations.

3) Granulation and sizing: Sometimes the different ingredients of the formulation do not mix well and segregate during homogenization. Therefore, it is desirable to granulate powdered ingredients by compression, dry granulation or in the presence of a binder under wet conditions. Most spectroscopic uses focus on the determination of water during wet granulation or drying after granulation.

4) Extrusion: NIR spectroscopy has been widely used in hot extrusion to monitor both API content and solid state of extrudates and to identify interactions between ingredients.

5) Tableting: This stage of the process is the closest to the final product. Therefore, it is sometimes easier to control the quality of the product directly in the press, especially if there is a subsequent coating step. At this point, NIR can also play an important role.

6) Coating: The coating process is a crucial step in the manufacture of solid oral preparations. In fact, the coating can act as a physical screen to avoid the effects of oxidation, moisture and lighting conditions in order to improve the stability of the final product or intermediate products in the process. The coating can also play an active role in the protection (gastroresistance) and release (modified release) of the drug in vivo. The homogeneity and thickness of the coating are important in controlling the timing of drug release. Many offline techniques are available to control the coating thickness, such as changes in weight, height or diameter of the coated granule/tablet cores during processing. In-line NIR technology is especially useful for monitoring water-based coatings and is a technique that saves hours of analysis, which we have discussed in particular in this other article.

7) Final product control: An important part of final product quality control includes the analysis of all batches produced to avoid out-of-specification results. This control point, although it is too late to avoid losses, can also be performed with portable (handheld) NIR tools and in just seconds analyze dozens of units (homogeneity, concentrations or other parameters) at the line.

Real-time Raman spectroscopy applications

As we will see below, this analysis technique has some applications similar to NIR spectroscopy and others very different because it is a technique with a much higher precision than NIR and that IRIS Technology uses in the systems we manufacture when we work with APIs with very low concentrations (typically <0.5) or in aqueous matrices where the amount of water generates a lot of noise in the analysis with NIR equipment.)

1) Raman spectroscopy for API identification: As each API has its own Raman characteristics, Raman spectroscopy can quickly and accurately identify the active ingredients, has a very low prediction error and in some cases has a detection limit as low as ppm.

2) Raman spectroscopy for the quantitative and qualitative analysis of formulations: The composition of pharmaceutical preparations is relatively complex; however, Raman spectroscopy remains one of the rapid detection methods if the excipients are simple or just an aqueous solution.

3) Raman spectroscopy for detection of illicit substances: Raman spectroscopy can be used for trace detection due to its sensitivity, speed and accuracy. In general, small amounts of illicit drugs cause drug safety incidents, and Raman spectroscopy can be used for illicit drug detection.

Benefits of applying NIR and Raman technology in production lines

In general, there are two fundamental advantages of Raman spectroscopy and NIR technology on production lines over traditional laboratory methods:

The first advantage would be the monitoring of continuous manufacturing. The pharmaceutical industry works mainly in such a way that the final drug is the result of several independent production steps. These can also take place in different geographical areas, which entails shipping and storing the different intermediate products in containers until the next manufacturing facility. This increases the risk of degradation over time or due to environmental conditions (light, humidity, etc.). One way to address this problem is to move from independent batch work to continuous manufacturing with the help of monitoring technologies such as real-time analytical control equipment.

A continuous process or continuous manufacturing is one in which materials are continuously loaded into the system, while the final product is continuously unloaded. Unlike stand-alone batch manufacturing, this concept involves the total connection of production units, with the use of PAT systems, along with process control systems to monitor and control the integrated manufacturing plant. Continuous process units are usually more efficient, more productive, with reduced volumes and less waste compared to classical process units. Therefore, these types of production units can respond more quickly to drug shortages or sudden changes in demand or needs (such as in a pandemic). In addition, their small size allows them to be transported directly to where the drugs are needed. However, a thorough understanding of the process, including the different connections between its processing units, is necessary.

The second major advantage is to reduce sampling and analysis time, and this is very important in biotech processes in their research, development and production phases. So far, most of the data are obtained with off-line instruments and methods.

Specifically for Raman, Raman spectroscopy is a powerful instrumental technique used in various types of pharmaceutical analysis. The superiority of the technique depends on the molecule of interest, the concentration level, the matrix or solution, other interfering species present and the desired sampling method. For many applications, Raman spectroscopy may be the best answer for identification and spectroscopic control needs. The role of Raman spectroscopy as a quantitative analytical tool is increasing due to the simplicity of sampling, ease of use and applicability to aqueous systems.

As manufacturers and system integrators of systems that operate with Raman and NIR spectroscopy, IRIS Technology collaborates with numerous pharmaceutical, foodstuffs, chemicals, among others, companies in the development of analytical solutions and the implementation of control systems, in turnkey projects ranging from technology, adaptations that may be necessary, data modeling, installation, validation and even homologation.

Here you can find the complete range of Visum® analytical equipment.

We hope this article has been of interest to you and as always, if you have any questions or even suggestions, you can write to us at news@iris-eng.com.

By IRIS Technology Solutions

Artificial Intelligence as a Predictive Maintenance tool

Together with the company mAbxience, specialized in the development, manufacture and marketing of biopharmaceuticals, we developed data models based on supervised machine learning techniques that after 4 years of work resulted in an AI-based Predictive Maintenance System in the plant facilities of the water for injections (WFI) process of mAbxience in Spain, published in the January-February Edition of the Pharmaceutical-Engineering Magazine.

The work demonstrates the effectiveness of machine learning models, built from the information generated by 31 sensors, 14 alarms and water quality indicators, to identify and predict anomalies within a warning time window (14 days) that is feasible for the preventive and predictive maintenance teams to make the corresponding adjustments in the areas and components of the plant identified by the algorithm.

Initial results show that the models are robust and able to identify the chosen anomalous events. In addition, the rule induction approach to machine learning (a technique that creates “if-then-else” rules from a set of input variables and one output variable) is “white box”, which means that the models are easily readable by humans and can be deployed in any programming language.

IRIS thanks mAbxience and the WFI plant technicians for their collaboration.

Read the full article here.

By IRIS Technology Solutions

IRIS presents new PAT applications for the pharmaceutical industry

IRIS Technology presents in Farmespaña Industrial applications of its PAT analyzers for the pharmaceutical and dermo-cosmetic industry.

Real-time content uniformity.

Real-time bioavailability.

Fluorescence-free Raman.

Read the complete note here.

By IRIS Technology Solutions

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Visum Palm GxP: The New NIR Analyzer for Pharmaceutical

Visum Palm GxP: The New NIR Analyzer for Pharmaceutical

Why Choose a NIR Analyzer for Pharmaceutical Applications

Key Features of the Visum Palm GxP: Technical Specifications

Regulatory Compliance and Data Security

Visum Master™ GMP Software: Intelligence Applied to NIR

Accessories to Expand the Potential of the NIR Analyzer for Pharmaceutical Use

Use Cases for the NIR Analyzer for Pharmaceutical Visum Palm GxP

Raw Material Identification

Content Uniformity and Quantification

Real-Time Process Control

Batch Release

Research and Development

Advantages over Other Portable NIR Analyzers

Conclusion

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Development of the Predictive Model with Visum Master™

Results and Evaluation of the Raman Predictive Model for Residual Ethanol

Conclusions

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Why Visum Palm GxP™ for pharmaceutical raw material identification?

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DS compound

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