Pharmaceutical and Biotech Manufacturing FAQs

Online product inspection encompasses a range of techniques to test raw materials, finished and packaged products for correct weight, completeness and freedom from foreign object contamination.  Thermo Fisher Scientific designs and produces online checkweighing, X-ray inspection and metal detection systems specifically tailored to meet the needs of pharmaceutical producers.

The techniques are applied at multiple points: in tablet and capsule making, in bottle and vial filling, in the course of blistering, and during primary and secondary packaging.

Pharmaceutical packages tend to be both small and light in weight. At today’s high production speeds, a highly precise checkweigher is needed to help ensure that packages are complete—for example, ensuring cartons contain product information leaflets and the correct number of blister packs. The Thermo Scientific Versa Rx Checkweigher is a system designed specifically to meet the unique requirements of the pharmaceutical industry.

Yes. Checkweighers can be integrated with other equipment and software to provide a complete track-and-trace solution. The range of Thermo Scientific  pharmaceutical checkweighers has flexible communications for successful integration into such a system.

Pharmaceutical production environments are necessarily clean and highly regulated but foreign object contamination of final product can still occur. Potential contamination sources include raw materials, metal fragments from wearing of machinery such as tablet presses, and objects inside containers prior to filling.  Contamination can also come from damage to products during manufacture.

Metal detection systems designed specifically for pharmaceutical applications are available.  A typical foreign-object metal detector contains a transmitter coil (or coils) that sends out a radio-frequency signal.  Two receiver antennas are equally spaced to either side of the transmitter. The transmitter-receiver array is mounted around an aperture through which product will pass. When no magnetic or conductive materials are present inside the aperture, the system is balanced and there is no difference between the signals at each receiver.  When metal travels through the aperture it creates a detectible imbalance, allowing for detection of metal contamination.

Metal detectors are most commonly used to check capsules or tablets after filling and forming, either after tablet presses or dedusters. Other applications include checking bulk powder ingredients in tubes and inspection of packaged, or partially packaged goods on conveyors.

A certain amount of flexibility is important to derive the most value from a pharmaceutical metal detection system. The Thermo Scientific APEX 500 Rx Metal Detector, for example, is fitted with wheels and handles so that it can be easily moved between production areas and cleaning areas. The system also has high levels of adjustability for height and angles, so it can be quickly optimized for use on different pieces of production equipment as needed.

In some applications vision-based systems can be used, but contaminants in opaque products or containers cannot be inspected in this way. In such applications X-ray inspection is a powerful tool that can perform the required inspection.

Pharmaceutical X-ray inspection systems are based on comparing the density of the product and the contaminant. X-rays are very short wavelength, very high energy light waves. As an X-ray penetrates an object it loses some of its energy. A dense area, such as a contaminant, will reduce the energy by a greater extent. As the X-ray exits the product, it reaches a sensor. The sensor then converts the energy signal into an image of the interior of the product. Foreign matter appears as a darker shade of grey and this distinction aids in identification of foreign contaminants. 

The same technique can be used to check fill levels and check packages for damage or check for metal contamination in metal containing packages such as blister packs.

X-ray inspection can be performed on packaged pharmaceutical and nutraceutical products as well as empty packages prior to filling. Typical applications include detection of glass contaminants in glass vials for lyophilized product, inspection of ampoules, inspection of blister packs for missing or damaged tablets or capsules, and inspection of powders in metalized foil pouches or large tubs sealed with metalized foil (when traditional metal detector solutions are ineffective).

Work has been done to simulate the effects of X-ray exposure from inspection equipment on APIs but, given the number of different APIs produced, such work does not allow for a definitive answer to this question. It can be stated that the X-ray energies used and the total exposure levels during the inspection process are low and so unlikely to have an impact on API quality, effectivity, or shelf-life. Should a specific product need inspecting, work can be done by system suppliers and producers to check whether a problem exists with that product.

Product inspection equipment is used in many industries, and Thermo Fisher Scientific has a long history in serving these applications. Additional information on the techniques can be found in the following FAQs pages:

• Checkweighers
• X-ray Inspection
• Metal Detection, also here

Mass spectrometers operate by ionizing neutral sample gas molecules. The resulting charged particle components are separated according to their molecular weight. In most commercial gas analysis mass spectrometers, ionization is achieved by bombarding the gas sample with an electron beam produced by a hot filament. To prevent collisions, the various ions are separated in a vacuum. 

The Prima PRO Process Mass Spectrometer is a high-performance gas analyzer based on a powerful and flexible scanning magnetic sector mass spectrometer. The platform has been designed to deliver superior analytical performance with high reliability and minimal maintenance requirements.

The Prima PRO Process Mass Spectrometer is recommended for several processes:

• Fermentation processes
• Cell culture processes
• Iron and steel processes
• Ethylene, ammonia, hydrogen production
• Ethylene oxide, methanol, polyethylene/polypropylene production
• Catalysis research
• Green hydrogen
• Direct air capture of CO2
• E-fuels
• Gas to liquids
• Solvent drying

Most Prima PRO Process Mass Spectrometers are equipped with a rapid multi-stream sampler (RMS), a highly reliable device that switches sample streams without compromising the quality of the sample presented to the analyzer. Known for rock-solid reliability, the RMS has proven to switch streams millions of times a year, year after year, with little or no maintenance.

When compared to traditional small molecule synthesis, biological processes are very complicated. Each cell is capable of carrying out thousands of chemical reactions per second, and often only one reaction will result in the target molecule.

How the reactions progress will be determined by a host of factors such as temperature, availability of nutrients, the amount of accumulated waste products, available oxygen, the concentration of enzymes that promote reactions and the amino acid building blocks from which proteins are made. With a simple fermenter, the growth medium is loaded following sterilization and the broth is inoculated with cells. Relatively stable sparge gas flow rates and impeller rotation rates are maintained to ensure sufficient oxygen availability throughout the medium. Once the cells start to multiply, excess heat is removed by cooling water, and adjustments of pH are made using acidic and basic reagents.

Dissolved oxygen (DO2) is monitored continuously, and manual assays are performed to assess cell density and substrate composition. If DO2 falls below a predetermined level, an additional shot of oxygen can be added by opening the oxygen valve for a brief period. In mammalian cell culture, a similar control methodology can be used for dissolved carbon dioxide (DCO2).

Statistical process control (SPC) tools are used to determine if the process follows an appropriate trajectory based on data that is manually entered from the lab assays. This data is also used to determine the appropriate time to harvest. Under these circumstances, batch-to-batch variation can be significant and an order of magnitude difference is not unusual.

With pharmaceutical products, if the recovered active pharmaceutical ingredient (API) falls below a certain quality standard, the entire batch must be scrapped. Clearly, the Prima PRO Process Mass Spectrometer, a highly reliable online PAT provides lab personnel with the tools needed to considerably improve product quality and increase profitability.

First, let us recap the basic means of bioproduction: Most bacteria used for biological production require water, carbon, nitrogen and a source of energy before they can grow and divide. They also have temperature, pH and gaseous requirements. The nutrients are provided in a complex growth medium that may include a number of natural products, or the media can be chemically defined for processes where natural batch-to-batch variation will present a problem. Both types of media are designed to provide the most appropriate concentration of nutrients to encourage rapid logarithmic growth until a target cell density has been achieved. At this point, the primary carbon source should be depleted to force the cells to switch to a secondary source that promotes product formation. Additional components can be included that either inhibit or induce particular metabolic pathways in order to maximize product formation and minimize accumulation of toxic byproducts.

A typical scenario for process development uses multiple benchtop bioreactors or fermenters with capacities in the one-to-10-liter (L) range. Various broth recipes are paired with different cell lines to determine the most robust and potent combination. Once the best candidate groupings are selected, the process is scaled up to the 200L scale (the pilot-scale) where potential control variables are fully tested for permissible range and efficacy. In addition to pH, temperature, agitation RPM, DO2 and DCO2, potential control variables may also include nutrient feed rates, back pressure, overlay gas composition, sparge composition and flow rate.

To control nutrient feeds and gas compositions in real time, it is necessary to either monitor the chemistry of the broth or the gas composition of the reactor effluent in real time. Model-based advanced process control techniques can subsequently be used to make changes to these additional control variables in response to measured changes in certain output variables. Fourier transform near infrared (FT-NIR) spectroscopy is a suitable technology for measuring liquid concentrations. The best technology for making gas concentration measurements is the magnetic sector mass spectrometer, a critical component of the Prima PRO Process Mass Spectrometer that significantly increases the analyzer’s performance and flexibility.

The most frequently used methods for determining cell mass, product concentration (titer) and substrate concentration rely on the use of differential equations. These ‘state equations’ are interdependent and must be solved simultaneously to produce valid results based on initial conditions and real-time measurements. The initial conditions include initial mass of substrate (the primary carbon source), starting cell mass and broth volume. The real-time measurements include oxygen uptake rate (OUR), carbon dioxide evolution rate (CER), respiratory quotient (RQ) and measured dissolved oxygen. The outputs from the models are typically used to track progress of each batch by comparing the results with the known trajectory of a ‘Golden Batch’ which provides an ideal profile for optimum product formation. This methodology ensures that limiting conditions and/or contamination can be identified and corrected as quickly as possible.

There are several emerging, advanced methods for implementing Model Predictive Control (MPC), including hybrid combinations of formal (deterministic) models and Artificial Neural Networks (ANN). Essentially, the ANN models fill in the gaps where first-principle analysis fails. ANNs are so called because their structure is based on layers of interconnected nodes, similar in structure to the neurons of the brain. These networks model behavior based on historical performance. The large training data sets often show that outcomes are the result of process variables falling within a range. While it might be very difficult to derive a formal explanation of the linkage, these relationships can still be used for process control.

The Prima PRO Process Mass Spectrometer enables extended analysis of the bioreactor effluent, and subsequently provides the data necessary to train these neural networks. Other mathematical modeling techniques include Principle Component Analysis (PCA) and Partial Least Squares (PLS) regression, both of which are mathematical procedures for investigating patterns and relationships in large data sets. By facilitating data compilation, the Prima PRO Process Mass Spectrometer is a key component in successful MPC implementation.

The time spent measuring the concentration of each component in the gas stream is software-configurable, enabling the trade-off between speed and precision to be varied depending on the number of sample points and the dynamic nature of each process being monitored. A typical analysis time is five seconds for the measurement of nitrogen, oxygen, argon and carbon dioxide (plus an additional three seconds for the measurement of methanol and ethanol, for example). In addition, five seconds of flushing time are added, resulting in a 10-second total analysis time per stream (or 13 seconds for the inclusion of methanol and ethanol). Since the progress is slower in mammalian cell culture than in microbial fermentation, the bioreactors can be monitored more precisely and less often than the fermenters.

The most important variable calculated from vent gas analysis is the Respiratory Quotient (RQ). It is the function of two distinct types of activity present in both fermentation and cell culture: growth and maintenance. RQ is defined as the carbon dioxide evolution rate (CER) divided by the OUR. The Prima PRO Process Mass Spectrometer provides timely estimations of RQ that can be used to determine the current metabolic activity and potentially to enable closed-loop control of certain variables, including the Glucose Feed Rate (GFR).

The oxygen concentration of the sparge gas and reactor effluent that is provided by the Prima PRO process mass spectrometer are sent to a process control computer. The data are combined with flow measurements and batch volume for the computation of culture oxygen uptake. The real-time calculation of the Oxygen Uptake Rate (OUR) is often used to determine the viable cell density in seed tanks, enabling determination of the appropriate time for inoculation. Using the Prima PRO Process Mass Spectrometer, the OUR measurement enables continuous kLa estimation.

The oxygen mass transfer will change as the viscosity of the broth changes. The microbiologist needs to understand this relationship before moving to pilot scale. Once the dynamic nature of kLa is understood, deviations from the normal trajectory can be used to detect and correct DO2 probe drift. By monitoring changes in kLa, the Prima PRO Process Mass Spectrometer enables personnel to more easily control agitation RPM, sparge flow and sparge oxygen concentration.

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.

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 requires that individual samples be taken from all incoming containers and an identity test be performed on each sample. PIC/S Annex 8 guidelines represent 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 help 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 Analyzer examines all the components of a pharmaceutical dosage form, including 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 the TruScan RM Analyzer an ideal tool for rapid detection of counterfeit pharmaceuticals in the field.

High-throughput screening (HTS) in the pharmaceutical industry involves testing collections of hundreds or thousands of samples and performing subsequent analyses, 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 minimal 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: 

 See more details in Raman: In-Depth Focus.

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, 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.

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. The TruScan RM Analyzer 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.

• Thermo Scientific TruScan RM European Pharmacopeia (EP) Chapter <2.2.48> — Raman spectroscopy statement of compliance.
• Thermo Scientific TruScan RM United States Pharmacopeia (USP) Chapter <1120> — Raman spectroscopy statement of compliance
• Thermo Scientific TruScan RM support for 21 CFR part 11 compliance

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 ease with which it is swallowed, 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 use 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.

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.

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.

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 (NIR) 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.

Thermo Scientific TruScan RM United States Pharmacopeia (USP) Chapter <1120> — Raman spectroscopy statement of compliance.

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.

The IonicX Portable XRF Analyzer is an X-ray fluorescence spectrometer. XRF is a non-destructive analytical technique used to determine the elemental composition of materials. XRF analyzers determine the elemental composition of a sample by measuring the fluorescence (or secondary) X-ray emitted from elements in a sample when those are excited by a primary X-ray source. Each of the elements present in a sample produces a set of characteristic X-ray lines ("a fingerprint") that is unique for that specific element, which is why XRF spectroscopy is an excellent technology for qualitative analysis of material composition. (For more information about XRF, download this ebook: Portable XRF Technology for the Non-Scientist.)

Pharmaceutical manufacturers employ the IonicX Portable XRF Analyzer for raw material analysis of ionic salts in the manufacturing of pharmaceutical products. A non-expert operator can use a portable IonicX Portable XRF Analyzer to accurately verify the identity of ionic salts far faster than conventional bench-based techniques. The efficient use of IonicX Portable XRF Analyzer streamlines material verification and makes material inspection cost-effective while maintaining high quality standards.

No knowledge of underlying analysis technology (XRF theory) is necessary to successfully implement the IonicX Portable XRF Analyzer following method validation. Operation requires only a general familiarity with the interface. However, given the nature of the device, it is recommended that all operators receive radiation safety training to minimize any risk associated with improper handling of the IonicX Portable XRF Analyzer.

Each year plant personnel spend considerable resources moving materials to be sampled to a controlled location, performing analysis with trained personnel in a laboratory setting, documenting samples, and moving materials into a quarantine area to await laboratory results. With the IonicX Portable XRF Analyzer, incoming materials may be verified in the warehouse, by-passing all the traditional central laboratory testing steps. This saves time and conserves manufacturing resources such as personnel, plant space, and inventory costs.

QC laboratory testing is also resource intensive. Highly qualified lab personnel spend numerous hours preparing and analyzing samples, reviewing data, and documenting procedures and results. Identity testing occupies valuable instrument time that could be used for other analyses. Chemical disposal fees add to laboratory costs. By using non-destructive, portable XRF analyzers like the IonicX Portable XRF Analyzer, pharmaceutical manufacturers can minimize these costs.

When the IonicX Portable XRF Analyzer is in use, the instrument emits a directed radiation beam when the tube is energized. Reasonable effort should be made to maintain exposures to radiation as far below dose limits as is practical. This is known as the ALARA (As Low as Reasonably Achievable) principle.

Three factors will help minimize an operator’s radiation exposure: time, distance, and shielding. While the radiation emitted from the IonicX Portable XRF Analyzer in unprotected conditions is similar to the exposure received in a conventional medical or dental X-ray, the IonicX test stand provides a means of mitigating the radiation, keeping any exposure at safe levels.

Unlike comparable ionic salts RMID analyzers (e.g., LIBS), the IonicX Portable XRF Analyzer does not require the preparation of a compressed pellet to operate. Instead, the IonicX Portable XRF Analyzer utilizes widely available sample cups of marginal cost, which are simply filled without prior preparation or alteration of the sample itself. These cups are composed of an assembled plastic frame and a polypropylene film, which forms a ‘window’ through which the analysis takes place.

Yes, the IonicX Portable XRF Analyzer can be mounted in two distinct test stands: the portable test stand, which allows increased stability for maximized workflow, and the mini test stand, which provides a small footprint while maintaining complete functionality. Images and further descriptions of each test stand are available on the IonicX Portable XRF Analyzer product page here.

Yes, the IonicX Portable XRF Analyzer is rugged and splash resistant (IP54 compliant) and has a dustproof housing for harsh environments. This is all commensurate with the device’s intended capability to provide laboratory-quality results anywhere in the manufacturing plant.

Weighing just 2.8 lbs (1.3kg), the IonicX Portable XRF Analyzer can be moved throughout operating facilities without the need for recalibration or modifications. With data transfer over secure Wi-Fi, the instrument can be used at any location.

The area of analysis is typically 8mm in diameter, helping to ensure homogeneous representation of raw material.

The IonicX Portable XRF Analyzer uses batteries that are designed to be hot-swappable. In order to allow battery substitution with no down time, capacitors in the analyzer maintain instrument functionality for 5-10 seconds after the battery has been removed.

Yes. Wi-Fi is used to connect the IonicX Portable XRF Analyzer to public and private wireless networks through wireless access points (WAPs) such as Wi-Fi routers and other hotspot devices. Unsecured networks are not supported.

Bluetooth connectivity is enabled from the settings page of the analyzer’s touch screen and can be used to establish a wireless connection between the IonicX Portable XRF Analyzer and a portable printer or barcode scanner.

The IonicX Portable XRF Analyzer comes with a locking shielded carrying case, two lithium-ion battery packs, one 110/220 VAC battery charger/ AC adaptor, check samples, a safety lanyard, and a PC connection cable (USB).

Yes. The IonicX Portable XRF Analyzer has enhanced 21 CFR part 11 compliance security features, such as user access restricted by usernames and passwords, password aging and complexity, full audit trail features, and the ability to securely sync data.

Pharmaceutical manufacturers use the TruScan RM Handheld Raman Analyzer for raw material analysis in the manufacturing of pharmaceutical products. A non-expert operator can use a handheld TruScan RM Handheld Raman Analyzer to accurately verify materials quickly. The efficient use of a TruScan Analyzer streamlines material verification and makes 100% material inspection cost-effective while maintaining high quality standards.

The TruScan Analyzer’s 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.

In addition, the TruScan RM Handheld Raman Analyzer is used by pharmaceutical manufacturers to identify counterfeits in order to protect patient well-being and brand integrity.

Falsified or substandard medicines are a growing problem worldwide. To protect patient well-being and brand integrity, pharmaceutical manufacturers use TruScan Analyzers to identify counterfeits. The TruScan RM Handheld Raman Analyzer allows 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 Handheld Raman Analyzer examines all the components of a pharmaceutical dosage form, including 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, providing detection of counterfeit pharmaceuticals in the field.

The TruScan RM Handheld Raman Analyzer can save manufacturing resources. Each year plant personnel spend hours moving materials into the sampling room, sampling them, documenting samples for tracking purposes and sending them to the lab, then moving materials into a quarantine area to await laboratory results. With the TruScan RM Handheld Raman Analyzer, incoming materials may be verified in the warehouse, by-passing all the traditional central laboratory testing steps. This saves time and manufacturing resources such as personnel, plant space, and inventory costs.

QC laboratory testing is also resource intensive. Highly qualified lab personnel spend numerous hours preparing and analyzing samples, reviewing data, and documenting procedures and results. Identity testing occupies valuable instrument time that could be used for other analyses. Consumables like sample vials and reagents along with chemical disposal fees add to laboratory costs. By using non-destructive, no-contact Raman handheld analyzers like the TruScan RM Handheld Raman Analyzer, pharmaceutical manufacturers can avoid these costs.

Traditional sampling and laboratory testing introduces production risks that have the potential to impact a product’s quality, yield, and production schedule. Opening a container to extract a sample increases its chance of material contamination and eventual rejection of the final product. Sampling and lab analysis adds variability to material release times. Samples may be accidentally contaminated, destroyed, lost, or mislabeled in a traditional central laboratory testing workflow. The variabilities of turnaround time for material inspection may impair the ability to forecast production equipment and personnel scheduling needs–this is a direct stress on plant productivity. Non-contact, non-destructive analysis by a TruScan RM Handheld Raman Analyzer reduces contamination risks and lowers production uncertainties.

The TruScan RM Handheld Raman Analyzer employs Raman spectroscopy, wherein 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.

The TruScan RM Handheld Raman Analyzer is built with a state-of-the-art optical platform paired with a field-proven embedded chemometrics engine. The patented, multivariate residual analysis offers a highly effective chemometric solution for material identification, with two spectral pre-processing options (1^st and 2^nd derivative), that is easy to operate in challenging environments and sampling conditions.

In addition to Raman technology, the TruScan RM Handheld Raman Analyzer has TruTools, an optional embedded chemometrics software package, with which users can build advanced, customized qualitative and quantitative methods for complex material analysis problems. TruTools models allow discrimination of multiple components, discrimination of raw materials with minimal spectral differences (such as Ethanol and methylated spirits), and discrimination of low API dosage tablets from placebos. With TruTools software deployed on a TruScan RM Handheld Raman Analyzer, non-expert operators can run advanced chemometric analyses anywhere in the plant.

The laser is a class 3B laser output of 250 mW +/-25 mW. The laser (excitation wavelength) is 785 nm.

The spectral range is 250 to 2875 Raman Shift (cm^-1). The spectral resolution is 8 to 10.5 cm^-1 (FWHM) across the spectral range.

The TruScan RM Handheld Raman Analyzer weighs less than 2 pounds (0.9kg)  and is ergonomically designed to increase comfort and productivity during inspections. It measures 8.2 in x 4.2 in x 1.7 in (20.8 cm x 10.7 cm x 4.3 cm).

The TruScan RM Handheld Raman Analyzer can be powered by a rechargeable lithium ion battery that provides about 3.5 hours power with normal use. 

Yes, the TruScan RM Handheld Raman Analyzer has an available factory library with over 4,300 samples of organic/industrial solvents, toxic chemicals, pharmaceuticals, household chemicals, and more. Using the factory library provides additional information for materials that fail a method run.

Yes, the TruScan RM Handheld Raman Analyzer comes with a nose cone, vial holder, tablet holder, vials and polystyrene rod, and also a battery, battery charger, cables, power cable adapters, card read, memory card, and Ethernet dongle.

The TruScan RM Handheld Raman Analyzer is rugged, fully sealed, and has an IP65 (Ingress Protection) rating, meaning that it’s dust tight and able to withstand water projected in powerful jets against the enclosure from any direction without harmful effects.  To remove nonhazardous contaminants from the instrument and the nose cone, wipe them with a soft cloth moistened with water, isopropyl alcohol, or a 5% solution of bleach (sodium hydrochloride). 

The TruScan Handheld Raman Analyzer is sturdy. It is built to Military Specification (MIL-SPEC) 810G, meaning it will survive a 1 meter drop. The screen is shatterproof.

No. The TruScan RM Handheld Raman Analyzer is calibrated at the factory directly in accordance with ASTM E1840-96 (2002), It does not require user calibration. Cyclohexane, acetonitrile, toluene, and acetaminophen bands are used to determine the x-axis calibration of the system, and this calibration is verified with acetaminophen (4-acetomidophenol), and polystyrene. All four of these materials are recommended in ASTM E1840-96 (2002). The laser output is also calibrated during the factory calibration procedures.

A polystyrene check sample is provided with TruScan RM Handheld Raman Analyzer for use in system performance verification (self-test). 

Yes, the TruScan RM Handheld Raman Analyzer has enhanced 21 CFR part 11 compliance security features, such as user access-restricted by usernames and passwords or biometric log-in, password aging and complexity, and full audit trail features. For more information on 21 CFR part 11 compliance read

Thermo Scientific TruScan RM Support for 21 CFR Part 11 Compliance.

Yes, the TruScan RM Handheld Raman Analyzer laser is 21 CFR part 1040 compliant and is certified to CE standards.

Yes, the TruScan RM Handheld Raman Analyzer is compliant with EP Chapter <2.2.48> and USP Chapter <1120>. To learn more on TruScan RM Handheld Raman Analyzer compliance, read the following documents:

• Thermo Scientific TruScan RM United States Pharmacopeia (USP) Chapter <1120>— Raman Spectroscopy Statement of Compliance
• Thermo Scientific TruScan RM European Pharmacopeia (EP) Chapter  <2.2.48> — Raman Spectroscopy Statement of Compliance

cGMP requires instituting strong quality management systems, obtaining appropriate quality raw materials, establishing proper operating procedures, detecting and investigating any product quality issues, and maintaining reliable testing laboratories.

PIC/S, Annex 8 PIC/S, Annex 8 requires that individual samples be taken from all incoming containers – 100% material inspection – rather than the traditional practice of composite sampling of a statistical subset of the batch, and an identity test be performed on each sample.

The TruScan RM Handheld Raman Analyzer meets cGMP requirements and the rigorous sampling demands of PIC/S Annex 8. TruScan RM Handheld Raman Analyzer allows non-expert users to identify and quantify raw materials, intermediates, and finished products on site in seconds. Replacing time-consuming, expensive laboratory sampling with a handheld Raman analyzers’ rapid verification of chemical compounds makes efficient and regulatory compliant material inspection possible.

Yes, the TruScan RM Handheld Raman Analyzer can scan through plastic bags, glass containers, blister packs and clear gel caps. TruScan RM Handheld Raman Analyzers’ point-and-shoot sampling is non-contact and non-destructive which minimizes the risk of cross-contamination and operator exposure.

Thermo Scientific TruTools is an embedded chemometrics software package that runs on the TruScan RM Handheld Raman Analyzer. It lets users build custom qualitative and quantitative methods for complex material analysis problems.

TruTools leverages Solo, a chemometrics software package from Eigenvector Research, Inc. that allows users to develop models that can be deployed onto the TruScan RM Handheld Raman Analyzer. Once deployed TruTools methods are selected through standard menus on the TruScan RM Handheld Raman Analyzer. No longer relying on a laboratory benchtop spectrometer, users can conduct advanced chemometric analyses anywhere in the plant.

Read about a TruTools method using a Principal Component Analysis (PCA) model to successfully identify similar chemical compounds such as magnesium stearate, calcium stearate, and zinc stearate in this technical note:
 Stearates verification using a handheld Raman analyzer.

The TruScan RM Handheld Raman Analyzer’s non-destructive point-and-shoot sampling principle facilitates rapid verification of a broad range of chemical compounds, including cellulose-based products.

The TruScan RM Handheld Raman Analyzer has been shown to help the European cosmetics industry meet the challenge of GMP compliance. In one case study, the raw materials used in cosmetics manufacturing include essential oils of natural origin. The TruScan Analyzer used in the study obtained 100 percent specificity on the raw materials tested. TruScan instrumentation also allows a user to check the formulations at various stages in the manufacturing process. You can read details of the study here:
European Cosmetics Industry Faces New Test in GMP Compliance.