Metrohm NIRSystems Dedicated near-infrared solutions Why near-infrared spectroscopy? 02 Near-infrared (NIR) spectroscopy is a versatile analytical More recently, attention has turned to analyzing solid technique and a well-known method for rapid, nondes-and liquid formulations for final product quality and in-tructive analysis on a wide variety of matrices across process control (IPC) of manufacturing operations. In this many industries. regard, NIR spectroscopy is a main spectroscopic tool used for process analytical technology (PAT) for the phar-In the pharmaceutical and chemical industries, NIR analy-maceutical industry. For the chemical markets, NIR spec-sis has been successfully implemented for many years, troscopy provides real-time information for monitoring with initial applications focused on raw material testing. and control of the chemical production processes and sol vent recovery systems. Benefits of NIR Spectroscopy Save analysis time, faster time to market • Results in seconds • No sample preparation – analyze samples as-is • Multiparameters measured simultaneously $ Greater and faster return on investment SAVE MONEY • No reagents, no waste – reduced analysis cost and no waste disposal • Versatile analyzer – many possible applications Improved product quality and manufacturing efficiency LITY CONTROL A • Quality of product can be controlled during all steps of manufacturing U Q • Fast analysis, real-time monitoring increases productivity and efficiency APPROVED Metrohm NIRsystems can be used in all areas of manufacturing, from raw Incoming Manufacturing Quality control Packaging raw material process laboratory Atline, at warehouse atline, inline, online offline, at lab offline, atline Metrohm NIRSystems Proven precise NIR technology 03 • 50 patents held by NIRSystems • Full scanning range, visible plus NIR, 400 nm to 2'500 nm Confident in application know-how • 50 years of NIR experience • Laboratory and process application knowledge • Global leader in reference analysis method Dedicated and well-established software • Vision software includes data acquisition, method development, and routine analysis in one package Excellent service and support • Exclusively represented in more than 80 countries, in more than 40 by Metrohm owned subsidiaries • Technical support helpdesk and regional support centers Practical approach to NIR data analysis and further information A good overview about NIR spectroscopic analysis and chemometrics in general can be obtained from our writ-ten monograph. Theoretical aspects of NIR spectroscopy, as well as many practical tips, are described in the monograph. Order this monograph, free of charge, from http://www.metrohm-nirs.com/Applications/ Metrohm order number: 8.108.5026 material inspection to in-process monitoring and final product release Incoming Manufacturing Quality control Packaging raw material process laboratory Atline, at warehouse atline, inline, online offline, at lab offline, atline 04 Pharmaceuticals NIR spectroscopy has been utilized in the pharmaceutical Quality control of intermediate products industry for many years and is recognized by interna-Less out-of-spec products manufactured, less re-work tional pharmacopeias like the United State Pharmacopeia time (USP), European Pharmacopoeia (Ph. Eur) and Japanese • Determination of blend homogeneity Pharmacopoeia (JP). NIR applications can be implemented • Detect the effects of granulation time into several Pharmaceutical processes, from raw ma te- • Real-time monitoring of drying process rials, to in-process monitoring and control to final pro duct release. Quality assurance of finished products Faster result without sample preparation and reduced Raw materials inspection workload of reference methods Compliant to GMP regulations, 100% testing of all • Determination of content uniformity incoming raw material containers • Moisture determination in lyophilized products • Identification of incoming raw materials without destroying the sample vial • Specification control of raw material quality • Determination of active ingredients • Counterfeit drugs detection 05 Chemistry Polymers NIR spectroscopy is sensitive to O-H, N-H, C-H, and S-H Due to NIR spectroscopic analysis requiring no sample bonds. Moisture determination is a common NIR applica-preparation and being nondestructive, many polymer tion. Reaction monitoring and endpoint determination and plastic attributes can be measured rapidly inline or using NIR spectroscopy provides real-time results to con-atline for qualitative as well as quantitative results. trol the process. Many applications that have historically Thermoplastics production, raw material purity, and been measured with physical property testing, like viscos-moisture content are common NIR applications. ity, may be measured with NIR spectroscopy, if the property is dependent on an intrinsic chemical characteristic, Control quality of raw materials such as chain length or cross linking. Control from first step for less problem in the process • Hydroxyl number Example of NIR applications • Acid, amine value • Moisture content • Identification of right materials (e.g., HDPE/LDPE) • Acid value • Hydroxyl number Polymerisation monitoring • Adhesive content Reducing over-processing of product improving • Antioxidants production consistency • UV inhibitor content • Reaction endpoint determination • Cure, melt index • Moisture content determination • Melamine content • Alcohol detection Determination of physical properties • Residual solvent detection Several parameters measured simultaneously • Molecular weight • Degree of branching • Tacticity • Melting point • Particle size verification • Density • Viscosity 06 Petrochemicals Education and R&D In petrochemistry, monitoring of the blending process by Although NIR spectroscopy is primarily used in produc-NIR spectroscopy has proven huge economical savings, tion-related app li cations, it has found widespread use in since crucial properties such as water content, density, research and development facilities. Pharmaceutical R&D viscosity, additive content, and hydroxyl number can be often uses NIR methods in pilot plant operations to help measured in less than one minute. evaluate daily processes. NIR spectroscopy can be used for different applications Common R&D parameters in petrochemical process starting from crude oil control, • Moisture content blending process and finished product control. • Coating thickness • Roller compaction hardness Gasoline parameters • Blend uniformity • Research octane (RON, ASTM D 2699) • Granulation • Motor octane (MON, ASTM D 2700) • Particle size verification • Road octane number (RdON) • Prediction of dissolution profile • Volume percentage or mole percent of paraffins, • Isoparaffins, aromatics, naphthenes, and olefins; PIANO) Common diesel parameters • Specific gravity • Viscosity • Flash point • Cold filter plugging point (CFPP) • Pour point • Cloud point • Cetane index 07 And more ... General NIR applications Pharmaceuticals Chemistry Petrochemicals Polymers Others: pulp & paper, textile, ink & paint, etc. Raw material Quality control of Quality control of Analysis of polyols Analysis of lignin in inspection raw materials raw materials wood pulp • Active ingredients • Substrates • Excipients • Fillers • Solvents • Additives • Packaging • Etc. Counterfeit drugs Measuring moisture Monitoring the Determination of Determination of detection, final pro- and residual solvent composition of additives in polymer hardwood/softwood duct determination levels in liquid and petrochemical and pellets content in wood solid matrices refining process products streams Assay of active Quality control of Lube base oil Analysis of Determination of ingredients fine chemicals analysis copolymer levels in finish on nylon fibers polymer pellets Analysis of residual Real-time reaction Fuel screening Determination of Monitoring moisture in a monitoring for end- finish on nylon fibers fermentation lyophilized pharma- point determination process ceutical product in fine and speciality chemical manufac- turing processes Conformity test of Determining the solid dosage forms: wet chemical tablets, capsules composition of cleaning, etching and stripping baths in the semiconduc- tor industry The application specialists of Metrohm NIRSystems have require practically no sample preparation and do not prepared a selection of Application Bulletins and Notes need any costly or toxic reagents. This application litera-for different industries that show the advantages of the ture can be downloaded from nondestructive NIR method: very fast measurements that http://www.metrohm-nirs.com/Applications/ Right choice for successful applications 08 NIR spectroscopy can be used to analyse different types of samples. Choosing the right measurement method, sampling module, and accessories is the most important step to developing robust NIR methods. Sample types NIR measurement methods Diffuse reflection NIR light penetrates into the sample and interacts with the sample. The NIR energy that is not absorbed is reflected back to the detector. • Suitable to measure solid samples without sample preparation Cream, paste, granulates, coarse, fine powders Diffuse transmission NIR light penetrates into the sample and interacts with the sample. Due to the particles, the light is scattered throughout the sample. The nonabsorbed NIR light is transmitted through the sample reaching the detector. • Suitable to measure solid dosage forms without sample preparation Tablets and capsules Transflection This measurement method is a combination between transmission and reflection. A reflector is placed behind the sample, used to reflect the nonabsorbed NIR light back to the detector. • Suitable for liquid samples Liquids, gels Transmission The sample is placed between the NIR light source and detector. NIR light is transmitted through the sample. The nonabsorbed NIR energy continues to the detector. • Suitable for clear liquids, suspensions, and solutions Liquids Examples of right measuring modules for 09 different sampling systems The modular design of Metrohm NIRSystems analyzers ensures that analyses are optimized for specific sample types. NIRS XDS RapidContent,MultiVial, and NIRS DS2500 Analyzer Measured using diffuse reflectance mode • The NIRS XDS RapidContent Analyzer and the Solids Module offer analysis of any solid form • The NIRS XDS MultiVial Analyzer provides the analysis of a tray of solids in vials • The NIRS DS2500 can analyse materials in bags or sample cups, with a rotation feature for non-homogeneous powders NIRS XDS MasterLab Analyzer Measured using diffuse transmission • The NIRS XDS MasterLab Analyzers perform auto-mated transmission and reflectance analysis of a tray of multiple tablets. Automated reflectance analysis of a tray of multiple vials is also possible • Integrated variable spot size for optimized sample illumination NIRS XDS SmartProbe, OptiProbe, and RapidContent Analyzer Measured using transflection mode • The NIRS XDS RapidContent Analyzer with the liquid sample kit offers liquid analysis using the gold diffuse reflectors • The NIRS XDS Interactance OptiProbe and the NIRS XDS SmartProbe offer the immersion probe with high energy mirror for liquid analysis NIRS XDS RapidLiquid and Transmission OptiProbe Analyzers Meausred using transmission mode • The NIRS XDS RapidLiquid Analyzer performs temperature-controlled transmission analysis of liquids in cuvettes or vials up to 65 °C • The NIRS XDS Transmission OptiProbe Analyzer is designed for laboratory monitoring of liquids. The optional Vial Heater Module allows more difficult samples to be analyzed up to 200 °C NIRSystems overview 10 Laboratory and atline analyzer Benefits Metrohm NIRSystems laboratory analyzers with their pa - tented monochromator can be operated in QC, R&D, and plant laboratories. Modular sampling accessories • Superior analytical performance allow for analyses of powders, granules, solids, slurries, gels, pastes, and turbid or clear liquids. The patented design of Metrohm NIRSystems analyzers • Seamless method transferability offer un paralleled performance and precise instrument matching to reduce your method development effort, minimize your implementation time and ensure seamless method transferability. • Shorten implementation time NIRS XDS series The next generation of NIR technology offering measurement flexibility through a hot-swappable feature. Each • Robust & reliable measuring module is easily exchanged, with no down-time, for the best performance of your application or sample type. NIRS DS2500 Analyzer The NIRS DS2500 offers the same broad wavelength range, 400 to 2’500 nm as the XDS, but in one dedicated, cost-effective solution. Developed for routine analysis in any environment, the DS2500 is suitable for use atline in the production plant Dedicated NIR systems for the best performance Laboratory analyzer, atline analyzer XDS XDS XDS XDS XDS XDS XDS XDS Rapid Rapid Interactance Transmision DS2500 MultiVial MasterLab RapidLiquid SmartProbe Content Content Solid OptiProbe OptiProbe Analyzer Analyzer Analyzer Analyzer Analyzer Sample type Analyzer Analyzer Analyzer Analyzer Powders • • • • • • • Coarse solids/ • • • • • • granulates Solids/film/paper • • • • • Tablets/capsules • • • • in reflection Tablets/capsules • in transmission Opaque liquids • • ▲ ▲ • • • Pastes/creams ▲ ▲ ▲ ▲ • • ▲ Viscous liquids/gels ▲ ▲ ▲ ▲ • • • • Clear liquids ▲ ▲ ▲ ▲ • ▲ ▲ • ▲ • Dedicated systems ▲ With transflectance options • Temperature controller up to 65 °C • Optional temperature controller up to 200 °C Features of Metrohm NIRSystems instruments Process analyzers 11 • Wide range of measuring options for dedicated The process analyzers provide near real-time process applications information while operating in harsh manufacturing conditions. The process sample interface is dictated by the • Hot-swappable modules offers flexibility to expand sample type and process conditions. Metrohm NIRSystems application anytime with NIRS XDS models offers 2 different types of process analyzers with several • Precise instrument matching, ensures that both sampling options. quantitative and qualitative methods can be trans-ferred directly from one NIR analyzer to another NIRS XDS Process Analyzer The XDS Process Analyzer is available in a variety of con- • Gateway to process figurations with one, four, or nine sampling points. De - • Covers different working conditions: atline, offline, pend ing on your sample characteristics, single fiber or inline, and online microbundle fibers are available. This economical way of performing remote measurements enables the analyzer • A new level of consistent and reliable instrument to be installed in an unrestricted area, reducing installa-performance, integrated diagnostic routines tion and operation costs. • Analysis while operating in harsh industrial environments NIRS Analyzer PRO The NIRS Analyzer PRO is a process analysis system based on high-resolution diode array technology. Three con-figurations are available; direct contact, fiber based, and non-contact. Process analyzer XDS Process Analyzer NIRS Analyzer PRO DirectLight/ SingleFiber MicroBundle Window reflectance Fiber DirectLight Sample type NonContact Powders ▲ • • ▲ • Coarse solids/ ▲ • • ▲ • granulates Solids/film/paper ▲ • • ▲ • Tablets/capsules in reflection Tablets/capsules in transmission Opaque liquids ▲ ▲ ▲ Pastes/creams ▲ ▲ • ▲ Viscous liquids/gels ▲ ▲ ▲ Clear liquids ▲ ▲ ▲ • Dedicated systems ▲ Different fiber optic probes are available NIRSystems software 12 Vision software Identification, qualitative, and quantitative methods are able Vision software. Precise and accurate analysis is ac - easily derived with the advanced, user-friendly, network-complished with the press of a key or click of a mouse. Dedicated requirement • Single or multi-user versions are available for different purposes, easily connected to the NIR analyzer via the network or direct connect. • Basic chemical version of software or compliant pharmaceutical version of Vision is available. All in one software • Spectral acquisition, method development, and routine analysis are included in one complete Vision software package. • Same software package for complete NIRSystems product line: laboratory, atline and process analyzers. All in one result • From one spectrum, get multicomponent results. Qualitative identification results and quantitative parameters obtained simultaneously from just one scan! Fully validated and regulation compliant • The pharmaceutical version of the software can be fully validated and is 21 CFR Part 11 compliant. NIRSystems reference standards and regulatory compliance To comply with regulatory requirements, regarding the tion (IPCTM) routines to verify analyzer performance. In 13 calibration, qualification, and verification of equipment ac cordance with industry recommended methods, all used for measurement and control of quality, XDS NIR tests are performed using NIST traceable standards pla - ana lyzers incorporate instrument performance certifica-ced at the sample plane. • Traceable standards • First offered in 1995 to pharmaceutical users • Designed to meet ongoing IQ/OQ requirements • Full record of successful testing Follow USP and Ph. Eur recommendation Metrohm NIRSystems offer the test for qualification of and spectroscopic noise tests). Software and traceable NIR instruments according to USP and Ph. Eur. recommen-standards are included in the pharmaceutical package. dation (wavelenght uncertainty, photometric linearity Support 14 Our worldwide support network of trained scientists, Compliance service wide range of customer care assistance programs, and Performed during the installation of your analyzer, comprehensive package of validation support services Metrohm insures that the NIR analyzer and the Vision ensures durable and efficient method development and software are working at peak performance. This service routine implementation for years to come. is provided by fully trained and certified personnel. Full IQ/OQ documentation is provided to the customer at the end of the installation. Additionally, Metrohm provides NIRS Instrument Performance Certification (IPCTM) to mea sure key performance parameters, and to verify their conformance to established specifications. These support include • IPCTM provides documented evaluation of parameters important for reliable instrument performance. It is performed at customer sites by a qualified IPC Engineer trained by Metrohm. • Professional installation and startup of a new instrument by compliant Installation Qualification (IQ) • Operational Qualification (OQ), guaranteeing that Metrohm instruments meet the equipment specification • A guideline for Performance Qualification (PQ) • Work-related training of users with subsequent certification Metrohm application support and literature Metrohm strives to provide the best support and service to all of our customers. Need help with determining the best NIR analyzer to fit your needs, or need help creating a library or calibration model? Call us! Metrohm has the most knowledgeable application scientists in the NIR busi ness. With a NIR technical support helpdesk and a dedicated techservices e-mail, we are here to help you with all of your application questions. 15 Service Metrohm Quality Service – worldwide Metrohm is exclusively represented in more than 80 of its investment and assurance of uninterrupted use of countries, in more than 40 of which we have our own the NIR analyzers. subsidiaries. This guarantees a tight network for sales and service. The Metrohm support team strives to pro-Metrohm Academy vide our customers with service that surpasses their ex - Training of our customers is critical to the successful im - pectations. plementation of an NIR method. Metrohm offers training in our facilities around the world. If you want to train Metrohm Care Contracts many users on the NIR analyzers, we can bring the train-Support plans and preventive maintenance contract are ing to you. available and represent your company’s best protection www.metrohm-nirs.com G, CH-9100 Herisau ohm A witzerland by Metr , printed in S SW 12 Subject to change Layout by Ecknauer+Schoch A 8.000.5111EN – 2013-