Pharmaceutical and biotechnology manufacturers must ensure the quality of materials—from incoming raw material through finished product. The Thermo Scientific™ TruScan™ RM Pharmaceutical Handheld Raman Analyzer delivers reliable material identity verification through sealed packaging in seconds, right at the point-of-need.
Here are some frequently asked questions and answers about the use of Raman spectroscopy in pharmaceutical materials testing.
A. In Raman spectroscopy, an unknown sample of material is illuminated with monochromatic (single wavelength or single frequency) laser light, which can be absorbed, transmitted, reflected, or scattered by the sample. Light scattered from the sample is due to either elastic collisions of the light with the sample's molecules (Rayleigh scatter) or inelastic collisions (Raman scatter). Whereas Rayleigh scattered light has the same frequency (wavelength) of the incident laser light, Raman scattered light returns from the sample at different frequencies corresponding to the vibrational frequencies of the bonds of the molecules in the sample.
If you wish to learn more about Raman spectroscopy, visit our online Raman Spectroscopy Academy, where you will find basic Raman tutorials, advanced Raman webinars on sample applications, and a helpful instrument guide.
A: In pharmaceutical manufacturing, Raman spectroscopy is suitable for incoming raw material identity verification, dispensing of materials during API manufacture, and counterfeit identification.
Pharmaceutical manufacturers use Raman for raw material analysis in the manufacturing of pharmaceutical products. A non-expert operator can use a handheld Raman analyzer to accurately verify materials quickly.
The Pharmaceutical Inspection Co-operation Scheme (PIC/S), Annex 8. PIC/S Annex 8 requires that individual samples be taken from all incoming containers and an identity test be performed on each sample. This is a major change from the traditional practice of allowing composite sampling of a statistical subset of the batch and identity testing of the single composited sample before releasing the batch to manufacturing. Individual container identity testing puts drastically higher demands on expert analysts’ time. The efficient use of portable Raman analyzers streamlines material verification and makes 100% material inspection cost-effective while maintaining high quality standards.
Raman analyzer QA/QC applications include enhanced raw material ID for similar compounds, multiple component ID, and identification and quantification of intermediate and finished products. In PAT, applications include at-line endpoint determination for distillations, reaction monitoring, and powder blending operations.
Falsified or substandard medicines are a growing problem worldwide. To protect patients and brand integrity, pharmaceutical manufacturers use portable Raman analyzers to identify counterfeits. Portable Raman analyzers allow users without chemistry training to conduct field-based screening of pharmaceutical samples and quickly and accurately identify falsified or substandard medicines. Because the spectrum generated by the TruScan RM examines all the components of a pharmaceutical dosage form: API, excipients, fillers, dyes, coatings, etc. to generate a spectrum representative of all components (and their relative concentrations) any slight deviation from the original formulation will lead to a detectable change in the resulting spectrum. This makes TruScan RM the ideal tool for rapid detection of counterfeit pharmaceuticals in the field.
A: High-throughput screening (HTS) in the pharmaceutical industry involves testing collections of hundreds or thousands of samples and subsequent analysis, in order to quickly assay the biological or biochemical activity of a large number of drug-like compounds. HTS techniques are used to characterize polymers and medicines by being incorporated into manufacturing processes to provide real-time measurements. Due to the large number of samples, HTS requires a high degree of automatization and small sample preparation. Raman spectroscopy fills this need and is used extensively for automated HTS and assay measurements. Read this article published by the European Pharmaceutical Review for more information:
A: Some pharmaceutical handheld Raman analyzers are expressly designed for setup and use by non-experts. For example, TruScan RM Pharmaceutical Handheld Raman Analyzers not only acquire the Raman spectrum of the material of interest but also – in real-time – determine the uncertainty of that measurement, given factors such as the sample characteristics, instrument telemetry, environment and testing environment. End users of field-material identification systems are not usually spectroscopy experts and, therefore, can rely on the instrument’s built-in algorithm to convert instrument data to a qualitative result.
A: TruScan RM analyzers are fully compliant with the revised standards in the European Pharmacopoeia Supplement 8.7 and the USP general chapter <1120> on Raman spectroscopy. TruScan RM has enhanced 21 CFR Part 11 compliance security features, such as biometric log-in and optional password aging and complexity, allow users to customize the analyzer’s security settings to exceed regulatory requirements.
A: Pharmaceutical companies that manufacture tablets, capsules and other solid dosage forms use a film coating on their products to differentiate visual appearance, to improve the ability to swallow and to mask objectionable tastes or odors. Film coatings also reduce tablet breakage and chipping as well as provide protection from light, moisture and environmental gases. While the latest handheld Raman analyzers have a built-in multivariate residual analysis decision engine to identify most materials, more complex materials analysis requires users to build custom, advanced methods. Some handheld analyzers utilized embedded chemometrics to enable users to create customized predictive applications, including classification, semi-quantitative and quantitative methods, that result in Pass/Fail criteria to identify highly similar compounds such as tablet coatings. Read more in the technical note:
Opadry verification using a handheld Raman analyzer.
A: Magnesium stearate is a white powder that becomes solid at room temperature. In the pharmaceutical manufacturing process, magnesium stearate is the most commonly used lubricant for capsules and tablets, and is used to help prevent pharmaceutical ingredients from adhering to manufacturing equipment. Calcium stearate, and to a lesser extent, zinc stearate, are also used as pharmaceutical excipients in manufacturing, primarily for tablet and capsule lubrication.
Magnesium stearate, calcium stearate and zinc stearate share a similar chemical compound structure and are more challenging to verify during the incoming raw material inspection process. While some pharmaceutical handheld Raman analyzers have built-in multivariate residual analysis decision engines to identify most materials, more complex materials analysis requires users to build custom, advanced methods. Those Raman analyzers that utilize embedded chemometrics can create customized predictive applications, including classification, semi-quantitative and quantitative methods, which allows users to develop models that can be deployed on the analyzer. Read more in the technical note:
Stearates verification using a handheld Raman analyzer.
A: Yes, the latest handheld analyzers can scan through plastic bags, glass containers, blister packs and clear gel caps. These analyzers’ point-and-shoot sampling is non-contact and non-destructive which minimizes the risk of cross-contamination and operator exposure.
A: In Raman spectroscopy, an unknown sample of material is illuminated with monochromatic (single wavelength or single frequency) laser light. The danger of using high-powered lasers must be recognized, especially when their wavelengths are in the Near Infrared area of the spectrum and, therefore, not visible to the eye. Fiber optic probes should be used with caution and with reference to appropriate government regulations regarding lasers and laser classes.
The laser used in the TruScan RM Pharmaceutical Handheld Raman Analyzer is class IIIb under the FDA CDRH classification system. Never point the instrument at yourself or others. Never start the instrument unless there is a sample fully covering the laser aperture. Always terminate a measurement prior to removing the sample from the laser aperture. Country-specific regulations with which the analyzer’s laser complies is available in the manufacturer’s user manual.
A: Although Raman is typically considered a nondestructive technique, conditions such as exposure time, laser power and the nature of the sample may lead to sample degradation. The energy transmitted by the laser depends on the duration of exposure and the wavelength. It may change the physical state and may destroy the sample.
Current field-based chemical identification instruments for pharmaceutical applications typically use one of three analytical methodologies: hit quality index (HQI), traditional chemometrics, or the probabilistic approach. These white papers explain the probabilistic approach of evaluation, giving specific examples.