Summary of the webinar

The pharmaceutical industry, due to its direct impact on public health, places crucial importance on the quality control of its products. This is particularly significant in the case of lyophilized vaccines, where aspects such as residual moisture content and the physical appearance of lyocakes are of strategic importance, directly impacting the stability and efficacy of the vaccine. The stringent quality control becomes imperative to ensure patient safety and meet the strict regulatory standards governing this delicate industry.

In this webinar, we will present a study conducted in collaboration with a client, whose anonymity, as well as that of the examined product, will be preserved for confidentiality reasons. The study focused on quantifying the residual moisture content in lyophilized vaccine samples and analyzing appearance defects such as cracks using spatially resolved near-infrared spectroscopy (NIR-SRS) and hyperspectral imaging. Sample were measured in the laboratory to demonstrate the capabilities of the SAM-Spec system at-line, with the future intention of real-time inspection of manufactured products directly in-line.

Presented products Indatech

• HypeReal: benchtop pushbroom imaging system for at-line NIR hyperspectral imaging
• SAM-Spec: spatially resolved NIR spectroscopy for high throughput in-line measurements

Summary of the webinar

The purity of an active pharmaceutical ingredient (API) is crucial in the pharmaceutical industry. Impurities can alter the effectiveness of the drug and lead to undesirable effects. This is why pharmaceutical regulations impose strict purity standards for APIs, requiring rigorous manufacturing processes and stringent quality controls. Process analytical technology (PAT) serves as a valuable tool for real-time monitoring of product quality attributes, enhancing the overall quality control process.

In this webinar, we will present a collaborative study between Indatech and Rowan University in the USA. The study focused on the utilization of Raman spectroscopy as a PAT tool for the in-line monitoring of the crystallization process of acetaminophen, a commonly used small-molecule API, and curcumin, a simulated impurity with low solubility and co-precipitation tendencies. The Raman results were used to calibrate a population balance model, enabling the prediction of the product’s purity evolution throughout the manufacturing process.

SPEAKER

Mitchell Paolello is a PhD student at Rowan University whose primary research interest is the diagnosis of impurity incorporation mechanisms in pharmaceutical crystallization processes. Most of his work is centered around investigating how impurities incorporate and are retained thermodynamically and kinetically, especially in the context of crystalline solid solutions. He has coauthored a published paper and submitted two papers on case studies of impurity retention mechanisms in both academic and industrial processes. His overall goal is to help improve understanding of the mechanisms in which impurity incorporation and retention occur in pharmaceutical crystallization systems with the purpose of enabling more robust process design. Before coming to Rowan, Mitchell earned his BS in Chemical Engineering at Drexel University and is also currently a co-op in the Solid State and API Engineering division at Boehringer Ingelheim.

Protein aggregation

Protein aggregation is one of the most frequent causes of protein instability. Considered a critical quality attribute, this is an essential indicator in drug manufacture, whether upstream or downstream.

The development and production of pharmaceutical products such as monoclonal antibodies may be affected by protein aggregation. This phenomenon occurs in various production, storage and sample handling conditions. As well, this occurs in a large range of protein concentrations and formulations. The presence of aggregated forms of proteins is potentially problematic for these therapeutic products. It brings with it a risk of immunogenic and pharmacokinetic problems.

Consequently, it is essential to fully characterize, quantify and check the level of aggregates, their nature and their distribution. In the context of an effective analytical inspection strategy for biological and biopharmaceutical products, these checks need to be performed regularly.

Characterization and inspection

Although most aggregates form during the upstream operations, they may also occur during the downstream processing, for example when unsuitable conditions have been selected.

Successful bioproduction therefore requires thorough knowledge of the processes and a rigorous definition of their parameters.

This is why, during this webinar, we will be explaining how our Asuryan UV-Vis spectrometer can be used to acquire knowledge concerning the processes, whether during the R&D phases to reduce the time-to-market, or directly inline for early detection of protein aggregation to avoid reduced product yields.

Proteins, which are highly reactive molecules, are present in small quantities. They require a spectroscopy method suitable for such low concentrations. Thanks to its high sensitivity, UV spectroscopy is ideal for this type of measurement.

Furthermore, the adaptability of the Asuryan’s UV spectroscopic measuring system enables various different probes to be used. These cover the wide ranges of protein concentrations encountered in the different industries and during the various steps for their production.

An acknowledged player in spectroscopy and the owner of a large number of patents, INDATECH has designed Asuryan, an inline measuring and inspection solution ideal for therapeutic production:

• Measurement sensitivity and accuracy at low concentrations,
• Repeatability over time thanks to an internal reference measurement,
• Simultaneous measurements at several points with different protein concentrations.

See all our case studies involving Asuryan.

Most food industries use sugar. Its purity depends on the final quality of the product, especially for beverages. The measurement of the color of sugar (in syrup or solid state) is the main criterion currently recognized. The international laboratory ICUMSA sets the standard for determining the amount of impurities.

Sugar industry is trying to increase the quality of their product to facilitate export and value. Especially true for some countries like Thailand or Brazil.

That is the reason why in-line sugar color measurement is becoming particularly critical to reduce reprocessing costs and gain efficiency. In order to meet this demand, INDATECH has developed an innovative solution capable of working on large ranges. Moreover, its solution meets the needs of both the sugar and the beverage industry.

This webinar is dedicated to sugar color measurement. It will present a collaboration made between NOVASEP and INDATECH. The sensor is directly integrated on filtration units that measure several wavelengths by LED technology.

Our specialist will present how to calibrate a sensor from the laboratory. After the calibration, he will explain the placement directly on the production line. An essential step for realizing a real time measurement in the process allowing an interaction and a piloting.

To know the composition of your liquids with accuracy, the SPOT4Line solution uses the LED light beam that penetrates the liquid to bring out its “optical fingerprint” and validate in real time several parameters.

INDATECH is a recognized player in spectroscopy and holder of numerous patents. It has designed SPOT4Line, the first multi-angle LED spectrometer dedicated to the analysis of all industrial liquids. Based on spectral scattering of light, SPOT4Line is completed by the patented SAM-SPEC Spatially Resolved Spectroscopy (SRS) technology to assign an optical signature to the liquid measured.

Discover all our application notes on the SPOT4Line.

This webinar will focus on physico-chemical characterization using NIR spectroscopy in industrial pharmaceutical, chemical or agri-food environments in order to characterize the granulation process. Also, NIR spectroscopy ensures easier continuous handling and better homogeneity of the blend under consideration. The disparity of the physico-chemical properties of the samples and their diversity require the measurement of several samples in a single operation. Which is why NIR hyperspectral imaging is used with Hypereal.

Then, it will be necessary to discover and characterize all the key steps in the compaction and granulation process during the process development phases. That is why this webinar will show how a hyperspectral imaging system can be used for physico-chemical characterization of these intermediate compacted products by indicating the compaction force applied to a powder blend, the proportion of API in the blend or the granule size.

The results are provided as an image, allowing the operator to gain a fuller understanding for optimization of the process and the machine.

HypeReal can be used to indirectly assess the chemical composition of the samples, their residual moisture content and other critical quality criteria, without destroying or modifying the sample and without using toxic reagents.

The unique HypeReal inspection system developed by INDATECH is an ideal tool for quick, non-destructive, laboratory-scale analyses of solid dosage forms.

Read the Case Study on physico-chemical characterization of powder blends.

With this webinar on NIR spatially-resolved spectroscopy, find out how to use NIR SRS spectroscopy as an effective PAT tool for the inspection of tablets with a low-dose formulation.

At this webinar on NIR spatially-resolved spectroscopy, we will be presenting the results of Residence Time Distribution (RTD) experiment. Tracers are used to represent the dynamics of the continuous processes. This is an appropriate methodology allowing control strategies. For this, the tracer must be selected appropriately. However, the selection criteria require similar behavior between the bulk material and the tracer.

Indeed, recent progress in increasing the sensitivity of PAT measurements allows “small” step to be made in the composition of the formulation. In this study our speaker, Carlos Ortega-Zuniga, used a low-dose formulation as the target. He induced small step changes to the API concentration in a continuous process.

For this experiment, the industrial tablet press is equipped with an NIR SRS system. The measuring instrument is therefore positioned after production of the tablets so that the individual tablets can be inspected. After these tests, the NIR SRS system proved sensitive to the capture of step changes of -/+ 0.50 % p/p of API.

To sum up, this work by a postgraduate from Rutgers University has demonstrated that small step changes can be performed to extract the RTD information. As a result, we can confirm that the inspection of low-dose tablets is possible using NIR SRS technology as the PAT tool.

For this purpose CA INDATECH has designed and developed patented technology combining NIR spectroscopy and hyperspectral imaging. This versatile analytical system is ideal for use in the laboratory or on continuous production lines. To learn more about our solution, attend to our webinar on December 15th, at 4 PM.