near-ir solutions for pharmaceutical development and manufacturing

Transcription

1 near-ir solutions for pharmaceutical development and manufacturing

2 2 3 understand and control your critical processes The current need for higher efficiency, lower cost of poor quality (COPQ) and faster time-to-market creates multiple pressures on pharmaceutical development and manufacturing organizations. It s becoming clear that better understanding and control of processes provides opportunities to develop better quality products and reduce operational costs in many areas. And that s exactly why many major pharmaceutical companies are using PerkinElmer s range of Near-Infrared (NIR) Spectroscopy products to help them achieve: Right-first-time formulation development Reduced scale-up delays and costs Faster time-to-market Faster troubleshooting Reduced raw material, work-in-progress and final product inventories Reduced cost of poor quality Counterfeit detection Advance warning of out-of-specification materials Faster product release NIR Spectroscopy is the ideal technique to implement at multiple points across your organization. It s fast, non-destructive, requires no special skills or sample preparation and pays back the initial investment rapidly. Industry regulators are convinced that NIR Spectroscopy is important too. The U.S. Food and Drug Administration (FDA) is supporting NIR implementation and has put in place a series of initiatives to encourage wider adoption in pharmaceutical development and manufacturing organizations. NIR Spectroscopy is also seen as a key measurement technique for process analytical technology (PAT) development. As a leading supplier of analytical instruments to the pharmaceutical industry, PerkinElmer offers a broad range of technologies for development and manufacturing. Application Analysis of metabolites in biological matrices Quantitation of trace impurities Degradation studies of active molecule Content uniformity Validation of process equipment cleaning procedures Dissolution tests Pharmacopeia tests on raw materials Packaging testing Contamination studies and production troubleshooting Color conformity testing for product and packaging Tablet dissolution studies Quantitation of residual solvents in raw materials Enantiomeric purity of drug compound Networked chromatography data management Complete laboratory information management Technology and UV/Vis Spectroscopy FT-IR and FT-NIR Spectroscopy FT-IR and FT-NIR Spectroscopy FT-IR and FT-NIR Imaging, FT-IR Microscopy UV/Vis Spectroscopy UV/Vis Spectroscopy Headspace Gas Chromatography Polarimetry Client/Server Chromatography Data Systems LABWORKS LIMS solutions Whatever the application, we re committed to providing rigorous compliance with FDA s 21 CFR Part 11 regulations, GAMP 4 and IQ/OQ validation assistance, as well as offering the industry s largest global service and support network. NIR Spectroscopy Each molecule s functional groups absorb Mid-IR radiation to generate a characteristic absorption or transmission spectrum that is typically rich in information and unique to that molecule. Spectra can be analyzed or searched against libraries of reference spectra to positively identify unknown materials. In the Mid-IR range, bands are often strong and samples may require dilution or thinning in order to measure usable spectra. In the Near-IR range, however, absorptions are due to overtones and combination bands of fundamental vibrations and are much weaker and broader. While spectra are less easy to interpret, a major advantage is that sample preparation is not required. This means that samples like pharmaceutical tablets can be analyzed directly and non-destructively. There are several types of NIR spectrometer, each suited to different applications. For highthroughput, in-process measurements, simple A comparison between Mid-IR and NIR Spectroscopy Features and Benefits how it works Mid-IR Spectroscopy filter instruments are often used successfully. Dispersive NIR spectrometers have also been used for QA/QC measurements. However, for materials quality and product development measurements in the lab or at-line, Fourier- Transform Near-IR (FT-NIR) Spectroscopy is now firmly established as the technology of choice. FT-NIR instruments have a wider operating range and work at higher spectral resolution, providing a wealth of important information not available to old-technology dispersive NIR systems. FT-NIR vs. Dispersive NIR 6.0 nm 3.0 nm 1.6 nm 0.8 nm 0.2 nm nm Spectra of talc in a glass vial measured from 0.2 to 6.0 nm resolution using a Spectrum One NTS. The extra spectral information is shown in the shaded box. Near-IR Spectroscopy Functional group interpretation Easy Difficult Commercial libraries available Many Few Qualitative analysis Easy Easy Quantitative analysis Liquids and thin films only Liquids, thin films and solids Sampling directly in containers No Yes Remote-sampling of bulk samples No Yes Sample preparation required For many samples No Non-destructive Sometimes Always A

3 4 5 multiple applications to improve process and product quality throughout your organization Pharmaceutical Development Pre-Clinical R&D Phase Clinical R&D Phase Manufacturing Phase Pharmaceutical Manufacturing Raw Materials In Process In Manufacture IND Bio-Statistics NDA Approval API Supplier API Discovery PK/PD Correlation Toxicology/ Carcinogenicity Metabolism Studies Drug Characterization Rapid API functional group identification. Spectrum One FT-IR Clinical Trials Phase 1 Phase 2 Phase 3 Phase 4 Clinical Trial Design Analytical Development Development of accurate, precise and robust FT-IR and FT-NIR methods for raw materials qualification and in-process testing. Spectrum One NTS, AssureID, Analytical Transfer QA/QC Methods Goods In Loading Bay, Raw Materials Lab, QA/QC Lab Verification of identity and quality of production materials or packaging. Spectrum One NTS, AssureID Excipient Suppliers Dispense Preblend, Granulate, Dry, Screening, Mill, Final Blend In Process Monitor process variations such as water content and active concentration in blends. Spectrum One NTS, AssureID, QA/QC Lab Test tablet for uniformity and active concentration. Press and Coat Process Lab Measure tablet active content and trend batch uniformity. Pack Release QA/QC Lab Test tablet for uniformity and active concentration. Synthesis Scale-Up Qualify raw materials and monitor reactions during API scale-up. Spectrum One FT-IR, Spectrum One NTS Formulation Development Fast, informative troubleshooting aids understanding of formulations. Spectrum Spotlight, Spectrum One NTS, API Process Development Product Development Manufacturing Process Transfer Example: wet granulation tablet manufacture Analytical Service Laboratories Failure analysis of blends, tablets and coatings leading to better understanding of materials and processes. Spectrum Spotlight and FT-IR Microscopy Clinical Trials, Validation and Pilot Production Batch Manufacture Verification of identity and quality of raw materials, intermediates, final products and packaging. Spectrum One NTS,

4 Near-IR Utilizing the latest advances in FT-NIR technology, the tablet autosampler offers a new approach to improving process and product quality in pharmaceutical tablet manufacturing. Rapid, non-destructive, whole-tablet analyses deliver vital information about active content and batch uniformity, meeting the demands of the industry and its regulators. The tablet autosampler can be deployed at many points throughout the development and manufacturing cycle, from formulation development to final product release. Incorporation of NIR measurements into a method during development or scale-up enables tighter control of quality, less waste and reduced rework costs during full-scale manufacture. A comparison between FT-NIR and Features FT-NIR Tablet Analysis improving Sample preparation Non-destructive Crush and dissolve Time per pablet Typically seconds Typically minutes Solvent required No Yes Chemical information Active concentration and Active concentration and content uniformity content uniformity Physical information Yes (e.g., hardness, No dissolution properties) Surface analysis Yes, using reflectance mode No Moisture content Yes No Low concentration impurities No Yes process and product quality Key Specifications 30-position autosampler Transmission and reflectance modes for full-tablet characterization Custom sample molds accommodate different-sized tablets and minimize stray light Controlled by AssureID software workflow design decreases operator error and reduces training costs Full technical compliance with 21 CFR Part 11 Custom Tablet ers For reproducible and accurate results, it is essential to minimize stray light in tablet transmission measurements, preventing light from passing around the side of the tablet and onto the detector. Special custom tablet holders easily accommodate various tablet sizes and shapes, ensuring a light-tight fit between tablet and holder. Transmission tablet holders, mold kit and 30-position tablet wheel. Results Browser File Edit View Tools Help Sample View: My Views - MyView1 Database Results FT-NIR tablet analysis at scale-up delivers significant savings during full production A major pharmaceutical company implemented FT-NIR tablet analysis in their production facility in order to better understand and control a tablet scale-up manufacturing process. After pressing and coating, samples were analyzed to measure active concentration and uniformity of composition across a production run. Using an AssureID PLS (Principal Least Squares) model, which had been built using 20 calibration samples and 60 validation samples of varying concentrations, batches of 10 tablets were analyzed. For each batch, statistics including individual Identifier/ Sample ID Analyst Name Analysis Date Quality Check Component1 Comp1 Resul Comp1 Calcu Comp1 Mean Comp1 SD Comp1 Mean Comp1 Quant Con 51 Developer 18 March, 2003 Fail Active_Prop rha_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD 53 rhb_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD 54 rhc_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD 55 rhd_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD 56 rhe_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD 57 rhf_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD 58 rhg_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD 59 rhh_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD 60 rhi_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD 61 rhj_cs.sp Developer 18 March 2003 Active_Prope NNPZXMD Comp1 Calculated Value Calculated Value Active Content / mg Sample Index-Date Order 3 x Std Dev 2 x Std Dev Mean: x Std Dev 3 x Std Dev and mean assay values, standard deviation, and maximum and minimum assay values were calculated and output to reports and the secure AssureID database. The standard deviation gives a measure of the uniformity of the blend. Further studies enabled the measurement and control of tablet potency and blend uniformity: During the run of a tablet press Between runs of a tablet press Between tablet presses With differing blend conditions Overall, significant savings in scrap and rework cost were made when the tablet was transferred to full production. Further studies using FT-NIR include the measurement of moisture content, coating thickness and tablet hardness, promising further process improvements and cost savings. 7

5 8 understanding solid dosage forms 9 Further Applications There are many other application areas where FT-IR and FT-NIR imaging can troubleshoot problems and lead to significant cost savings. Tablet stability studies Spectrum Spotlight offers blending process insight to improve quality and address regulatory concerns A major pharmaceutical company employed FT-NIR Imaging to gain insight into the blending process in tablet production. measurements on the active concentration showed that some batches exhibited poor content uniformity without any obvious reason. Dry powder electrostatic coating analysis The Spectrum Spotlight 350 system was used to investigate Spectrum Spotlight 350 FT-NIR Imaging System In tablet production, the microscopic distribution of ingredients is known to impact important quality parameters such as dissolution, stability, bio-availability and hardness. However, to date there have been no convenient techniques that can provide this information, which means that the blending and tabletting processes are often poorly understood, adversely affecting product quality. In both formulation development areas and the process analytical support functions, it is essential to be able to identify anomalous distribution of ingredients. FT-NIR imaging is rapidly being implemented by major Key Benefits Seamless automation simplifies setup and measurement, increasing productivity and reducing errors. Two-in-one detector enables single-point microscopy as well as IR imaging, allowing microcontaminants in products and packaging to be identified in seconds. Powerful built-in data processing routines automate data analysis and provide quick answers. Superb visible image quality ensures accurate and easy sample inspection. User-defined sampling area and aspect ratio allows you to match the image size to the sample size. Counterfeit detection Contamination identification Packaging development Transdermal patches and related delivery systems Chemical images of active distribution (red). Upper row: good blend uniformity. Lower row: poor blend uniformity. blends from good batches and problem batches. Samples were taken from the top, middle and bottom of the blender for each batch and images generated and compared for each. The images showing the distribution of the active component were particularly significant, showing clear differences between good and problem batches. In addition it was noted that the original active particle size was 11 m before blending, whereas aggregates times larger were observed after blending. This was thought to be an example of overmixing, in which particles attract each other to form large aggregates, having a detrimental effect on final product quality because the active ingredient cannot be uniformly distributed between tablets in the batch. pharmaceutical companies to help solve these and many other manufacturing problems. Full-range imaging from cm -1 covers the most information-rich areas of the spectrum, maximizing applications flexibility. In this example the new information provided by FT-NIR Imaging allowed process optimization and significant quality improvement, reducing costs and addressing regulatory concerns. Image pixel sizes of either 6.25 x 6.25 m or 25 x 25 m are available.

6 smart sampling for all applications Spectrum One NTS The Spectrum One NTS FT-NIR System is the instrument of choice for demanding manufacturing and product development applications in many pharmaceutical companies across the globe. Packed with innovative features that simplify analyses and ensure reproducible and error-free operation, Spectrum One NTS is equally at home in the laboratory, in the loading dock or on the factory floor. A wide range of sampling modules integrates seamlessly with Spectrum One NTS to provide simple, reproducible measurement for all materials. When inserted into the sample compartment, each module is automatically recognized and the appropriate hardware and software parameters are set up for instant analysis. No optimization or alignment is required before measurement, ensuring consistent performance. Remote fiber-optic sampling. Liquids sipper. NIRA with spinner. Sample Type and Application Tablets, powders, granular solids, blister packs, samples in glass vials, gels, viscous liquids Coarse and granular solids, inhomogeneous materials Automated liquid sampling Remote bulk sampling of powders, pastes and liquids Transmission and reflectance measurements on coated and uncoated tablets Microscale composition studies and trace analysis of all solid materials Viscous samples, resins and pastes Clear liquids Sampling Accessory Near-Infrared Reflectance Accessory (NIRA) NIRA with spinner Liquids sipper Solids and liquids fiber-probes Spectrum Spotlight 350 FT-NIR Imaging System Disposable transmission cells Quartz transmission cells AssureID The AssureID software suite verifies materials quality at all critical points in the manufacturing process, from incoming raw materials inspection to final product assay. AssureID s speed of implementation and simple operation facilitates increased testing, revealing key information about the quality of raw materials, intermediates and final products. Simple, Fast Method Development AssureID s workflow interface guides users through the development of new methods, integrating algorithm selection and validation in a series of easy steps. Depending on the application, measurements may be qualitative, for example Method Instrument Settings the verification of material Materials Untitled identity, or quantitative, such ID Model ID Validation Analysis Workflow as an assay of the active Introduction Sample/Batch Details Background ingredient. AssureID includes System Suitability Scan built-in expertise that can Analyze ID Analyze Quant Report automatically troubleshoot Finish during development and suggest ways to improve the robustness of the method. Permission levels allow each method to be reviewed and released by an authorized person using electronic signatures key components of AssureID s integral 21 CFR Part 11 compliance. Users, Groups and word Control Properties Users Groups word Control Group Name: Developers Members of the group are able to: New... Configure instruments 2 Setup and test instrument validations 3 Perform instrument validation 4 Read methods 5 Develop methods 6 Delete methods and folders 7 Copy and move methods 8 Approve methods 9 Run methods 10 View results 11 Approve results 12 OK Cancel Apply Delete Help Signature Points Signatures Signature Points Name Approve Report Signature required Prompt for comments Reasons Text Report is approved for publication Report is approved for internal use Report is complete and reviewed New... Apply User permissions (left) and e-signatures (right). OK materials qualification throughout your process Update All... Cancel Easy Implementation Released methods are based on simple analysis workflows that are easy to follow, eliminating operator error. Standard workflows include user messages, prompts and report templates and can even incorporate SOPs, multimedia training materials and local languages, making AssureID ideal for global manufacturing operations. Simple pass/hold decisions are reported along with further instructions. AssureID Analyzer - Rupert Aries Work Log Sample ID carb6.sp carb8.sp carb9.sp crosc8.sp crosc9.sp ph1av2.sp ph1av3.sp povid3.sp povid4.sp rc5av5.sp rc5av6.sp Add Comment... Sign Results... Material Type Unspecified Sodium Crosca Sodium Crosca Sodium Crosca Identified As Sodium Crosc Add a comment to the selected result. Sign all the results. Results from an analysis of raw materials. An AssureID SOP. Faster, More Informed Decisions Result Standard Operating Procedure for - Microsoft Internet Explorer File Edit View Favorites Tools Help Stop Refresh AssureID s databases provide rapid access to all raw data, methods and results, helping authorized analysts and managers to make faster, more informed decisions. The databases can be queried using multiple selection criteria to correlate information and reveal trends. Comprehensive graphing tools allow trends to be displayed on-screen or included in a report, allowing identification of, for example, a material or product moving toward the edge of its specification. Search Standard Operating Procedure Tablet Coating Spray Conformance Testing on the PerkinElmer Spectrum One AssureID System This is the Standard Operating Procedure (SOP) to be used as the basis for the qualification and authorization of all Intapharm tablet coating solution sprays. Results generated from modified versions of this procedure will not be accepted by the Intapharm Quality Assurance Department unless previously agreed to by the Quality Standards and Procedures Department of Corporate Quality Assurance. 1. Purpose & Principle 1. To determine that the chemical composition of a tablet coating sprays conforms to Intapharm specifications 2. Equipment & Supplies 1. PerkinElmer Spectrum One NTS AssureID system with NIRA ml glass vial, polypropylene screw-top lid. Intapharm part number SV_754. See "Production Lab Sampling Apparatus" for a detailed diagram and ordering information. 3. Access to Intapharm Production Quality Assurance System (QAS) 4. Bar-code printer 11

7 PerkinElmer, Inc. PerkinElmer, Inc., is a global technology leader focused in the following businesses Life and Analytical Sciences, Optoelectronics and Fluid Sciences. Combining operational excellence and technology expertise with an intimate understanding of its customers needs, PerkinElmer creates innovative solutions that accelerate drug discovery, enhance research productivity, help meet regulatory requirements, improve time-to-market and increase manufacturing efficiencies. PerkinElmer s OneSource SM Laboratory Services provides you with a comprehensive worldwide service offering that allows you to take care of business and set your sights on what matters most results. With over 1,000 factory-trained professionals serving more than 125 countries worldwide, PerkinElmer is your single source for instrument care and repair, validation services, software and hardware upgrades, education, and more. Online consumables, reagents and accessories ordering lets you get your hands on what you need fast. Additional information on PerkinElmer s NIR solutions is available at PerkinElmer Life and Analytical Sciences 710 Bridgeport Avenue Shelton, CT Phone: (800) (U.S.) or (+1) PerkinElmer, Inc. All rights reserved. PerkinElmer is a registered trademark, AssureID, LABWORKS and Spectrum are trademarks, and OneSource is a service mark of PerkinElmer, Inc. PerkinElmer reserves the right to change this brochure at any time and disclaims liability for editorial, pictorial or typographical errors _06 Printed in USA