News. Pharma & Biotech. Safe and Simple Weighing in API Repackaging Areas. Weighing and Analysis in the Laboratory

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1 Pharma & Biotech Weighing and Analysis in the Laboratory Analytical solutions in the laboratory 3 News Safe and Simple Weighing in API Repackaging Areas ACEF has invested in 6 new Active Pharmaceutical Ingredient (API) dispensing units, each incorporating an Excellence Balance. Its Quality Assurance Manager, Carlotta Bormioli, explains how METTLER TOLEDO s weighing solutions ensure operator safety and integrate into ACEF s quality control system. Invest for highest quality requirement ACEF, located in Fiorenzuola d Arda, Italy, specializes in the repackaging of chemical and pharmaceutical raw materials, is a market leader in the distribution of cosmetics ingredients, excipients, APIs and food additives. Their particular expertise lies in the flexible and safe repackaging of materials under strict quality control procedures. Incoming raw materials are inspected and analyzed before being repackaged, labeled and having a certificate of analysis issued. ACEF has recently invested in 6 downflow dispensing areas, incorporating 6 new Excellence Balances, for API repackaging in order to comply with the highest GMP quality standards. Simple and traceable weighing ACEF had the following requirements for the improvement of their balance operation and general weighing processes: Avoidance of cross contamination Short settling time Simple weighing procedure for operators GMP compliant documentation Reliable routine testing and maintenance Following the careful analysis of process requirements through METTLER TOLEDO s GWPBase recommendation tool, ACEF selected 3 XS6001S Precision Balances for weighing packages between 100 g and 5 kg, and 3 XS204 Analytical Balances for packages between 5 g and 100 g.

2 XS204 Analytical Balance ACEF, Fiorenzuola d Arda plant, Italy Katiuscia Ferdenzi operates the XS204 Analytical Balance in the down-flow dispensing area. Solutions that surpass requirements Carlotta Bormioli was very impressed at how the balance selection process took into account ACEF s specific Quality System requirements. She appreciated the easy cleaning concept of the XS204 Analytical Balance and decided that it was the correct balance for them. The draft shield XS6001S Precision Balance in down-flow dispensing area. can be fully dismantled in seconds and cleaned in a dishwasher. The weighing procedure ensures that no balance part is in direct contact with the sample reducing the cleaning validation to a cleaning verification. Despite the unfavorable weighing conditions caused by down-flow, the XS204 Analytical Balance s SmartGrid weighing pan contributes to short stabilization time and the XS6001S Precision Balance, with the larger weighing platform, performs excellently. Carlotta Bormioli appreciates all the additional features offered, including the standardized touchscreen user interface, which simplifies user operation. Bluetooth printers are located outside the dispensing areas in order to avoid paper contamination and meet the documentation requirements according to GMP. XS Balances are future-proof and support paperless documentation thanks to Ethernet connectivity and One Click data management solutions. Finally, METTLER TOLEDO provided ACEF with CarePac Routine Testing Weights and maintenance contracts in accordance with the GWP recommendation to complete all requirements. Publisher Mettler-Toledo AG Laboratory Division Im Langacher CH-8606 Greifensee, Switzerland Production Segment Marketing LAB Global MarCom Switzerland Subject to technical changes. Mettler-Toledo AG 02/11 Printed in Switzerland. 2

3 High Throughput Solutions for Biotech Research Current applications of modern biotechnology make specific use of molecular biology methods in order to optimize various experimental procedures. The number of high throughput experiments has, therefore, grown continuously over the last few years. Liquid-handling processes have also become more complicated as a result of the drastic reduction in the average volumes used. Accurate pipetting in 96 or 384 wells Ideal for ELISA tests A substantially higher throughput can be achieved with the time-critical ELISA (enzyme-linked immunosorbent assay) test procedure, which is the most commonly used experimental procedure for which the most techniques have been developed. Liquidator 96 - the new dimension in manual liquid handling Bench top pipetting system Liquidator 96 from METTLER TOLEDO Rainin is a manual pipetting system with 96 channels which is ideally suited to genomic, proteomic and cellular assays. Accurate and efficient, it is designed to optimize workflow without the need for complicated programming or dedicated technician time. It speeds up high throughput pipetting and delivers synchronized and precise pipetting from any kind of multi-well plate, reservoir or deepwell container into 96 and 384 well plates. Simultaneously pipetting 96 wells with the liquidator, guarantees precise results from series of experiments. The ergonomic Liquidator 96 system is easy to use and works just like a manual pipette. Neither complicated software nor programming is required. It guarantees reliable and reproducible results and, as a personal bench top pipetting system, is always ready to use for all lab employees. Its minimal footprint means that it will fit onto any bench or inside any laminar flow cabinet, making the system suitable for workflows requiring clean room conditions. Depending on the task in hand, ELISA can be used to identify proteins, hormones, antibodies, tumor markers, viruses and pharmaceutical products in serum, plasma, urine, stool samples or even cell cultures. In terms of antibodies, it can be used to precisely calculate the first antibodies to appear (IgM) or specific antibodies (IgG), for example It can also be used to investigate allergies (IgE) or establish the total volume of one particular antibody. The key requirement for perfectly evaluating ELISAs is to precisely dispense the volume of solution needed and to cleanly pipette using appropriate, contamination-free pipette tips. BioClean pipette tips from Rainin, produced under clean room conditions, are ideal for this. They are 100% contamination-free and, therefore, prevent irregularities and errors in experiments

4 Automated Dosing Capsule Filling for Pre-Clinical Trials In pre-clinical trials of new pharmaceuticals, manual weighing often involves highly potent and hazardous substances. The process also requires great concentration from the lab technicians and can be time consuming. Discover how a top pharmaceutical company automated the slow, hazardous and expensive capsule filling process for their pre-clinical trials. QS30 Autosampler Controlled handling of potential new pharmaceuticals The main goals of pre-clinical studies are to determine a product's ultimate safety profile. Studies involve in vitro and in vivo experiments through dynamic weighing and the use of wide-ranging study drug doses in order to obtain preliminary data. Dependant on the nature of drug and test subject, new pharmaceuticals are often administered via gelatin capsules where the fill weight of each capsule must be accurately calculated and prepared according to the test subject s weight. This involves manually, yet precisely, weighing in highly potent, hazardous substances with a spatula. For this pre-clinical trial with our customer, size 12 capsules were used (outer diameter 15.3 mm, height or locked length 40.5 mm and an actual volume of 5 ml). The manual preparation would have involved: Placing one capsule onto an analytical balance Manually weighing in the calculated dose for the specific subject by hand Recording the weight Removing the capsule from the balance Capping The study lasted for 28 days and involved 30 test subjects. The dose of the new pharmaceutical was calculated according to 70 mg of drug per subject kg. Between 1 and 3 capsules were applied to each test subject per day, totaling 1680 capsules over the course of the trial and 1.2 kg of API used. Each manual dose on a balance takes 2-3 minutes per capsule and, had the whole study been prepared manually, would have taken 84 hours to dose the samples. Challenges of manual dosing The customer realized that filling each capsule manually with a different drug dose according to the target subject s weight required great concentration from the researcher preparing the capsules. Various sample vessels for capsule to vial filling. 4

5 A list of doses for up to 90 capsules per day was created and each dose was processed individually. This high quantity of capsules led to capsule filling becoming a time consuming and tiring task with a high human error risk level. In addition, the pharmaceuticals being dosed into the capsules and handled by the researchers on a daily basis were not yet fully characterized. For this reason, the drugs needed to be handled as a high, unknown potency class in order to protect the researcher. Automated dosing solution The Quantos QB1 automated powder dosing system, installed with disposable dosing heads for 250 doses and combined with a QS30 Autosampler for up to 30 unattended doses, was an ideal solution. The greatest resulting value for this customer has been the increased throughput and time saving that automation brings. For this 28-day project, they saved a third of the time needed for manually filling 1680 capsules. Alongside these savings, the Autosampler enabled researchers to work on other tasks whilst up to 30 capsules were being filled simultaneously. To minimize the time each researcher is in contact with API, the dosing is performed in a closed system and the entire Quantos dosing unit can be placed inside a safety enclosure. Process safety is also a valuable benefit and this is guaranteed with the RFID chip in the dosing head used to store all key information relevant to the substance used, e.g. lot number or powder characteristics. Actual fill weights of each individual capsule are also captured electronically and can be printed if required. Unlike manual weighing, the Quantos system doses to an accuracy of ± 0.5 mg independent of substance characteristics and operator experience. ErgoDisc capsule caroussel. 5

6 In-process Particle Characterization Innovation Award for In-process Particle Characterization PROCESS, PharmaTEC and Schüttgut organized the 3rd edition of the Innovation Awards at Powtech/TechnoPharm The new probebased in-situ FBRM C35 measuring system from METTLER TOLEDO was awarded most innovative technology within the Particle/Material Analysis and Characterization category. One of the key issues when designing and scaling up such a process is the consistent distribution of product granule shape, size and density. These product characteristics are important for balanced granule flow properties, for the prevention of inhomogeneous distribution of the active substance and additional tablet quality issues. As reliable design and scale-up criteria for such granulation processes have not so far been available to scientists and engineers, they have had to rely on empirical values and product quality control. Figure 1. Development of the MeanSqr.Wt. as a function of time for an uncontrolled granulation process (batch 6) and several controlled batches (batches 7-10). The solid circles show the mean final values. These were achieved reliably within the 320 μm +/- 10% target range required for the controlled batches. Granulation process Thanks to its mechanical cleaning mechanism, the innovative in-situ FBRM C35 measuring system is the first instrument to provide reliable information concerning particle dimension, numbers and shape even at highly adhesive process conditions, such as those encountered during wet granulation processes. High-shear wet granulation is a common process in the production of oral solid dosage forms in the pharmaceutical industry. Process analytical technology The FBRM C35 can be used to optimize and scale up high-shear wet granulation as shown in the following example. Various parameters, such as liquid level, stirring speed, granulation time and spray rate, were systematically varied during a Design of Experiment (DoE) approach. The outstanding benefit of a robust process analytical technology (PAT) which is able to track particle dynamics during wet granulation is shown in Figure 1. It demonstrates the variations in the granule growth of different batches via the Mean Sqr.Wt., which represents the mean dimension of granule distribution. The objective of this set of experiments was to achieve a mean granule dimension of 320 μm +/- 10%. The uncontrolled batch 6 failed to reach the desired final granule dimension (final value 710 µm). Such significant variations can result in a total product loss which has dramatic conse- 6

7 Mechanical cleaning mechanism of the innovative in-situ FBRM C35 measuring system. quences for overall process costs. All other batches were controlled with FBRM C35 real-time particle characterization in order to achieve the desired endpoint. The new probe-based in-situ FBRM C35 from METTLER TOLEDO allows for reliable real-time quantification of particle dimension, number and shape during high-shear wet granulation processes. Using the C35 offers clear benefits for R&D, scale-up and control in pharmaceutical formulations: Shorter development times and therefore significant R&D cost reduction. Robuster processes and avoidance of failed batches. Improved product quality as part of a Quality-by-Design (QbD) approach. Dr. Oliver Hamann, Head of Advanced Development, Benjamin Smith, Market Development Manager and Dr. Markus Adamczyk, Productspecialist with the award-winning FBRM C35. 7

8 Online Tools Benefit From our Knowledge for Your Best Practices Discover 4 selected best practices from METTLER TOLEDO in mt.com. Profit from the useful, valuable yet free know-how from our experts to support your daily laboratory procedures and minimize risk of measurement. Good Titration Practice Discover the 5 major steps to Good Titration Practice. Comprehensive support and guidelines ensure the financial and time investment are always allocated appropriately whilst minimizing risks. Good Weighing Practice GWP (Good Weighing Practice ) is a risk-based approach that clearly interprets the regulations of each industry and puts them into straightforward weighing practice. This results in a simple program that assures compliance at any time. Risk Checker Diverse factors can affect titration results. Spend 5 minutes answering 8 questions, determine titration result reliabilty and save money. Movie See how One Click Titration simplifies daily lab work with its uniform and intuitive user concept. Brochure Order a copy of the 'Good Titration Practice ' brochure. The brochure focuses on how to perform optimum titration analysis. Risk Checker Find out if your results are continuously accurate. Simply answer 8 questions and the GWP Risk Check provides expert advice on how to optimize system quality. Movie Watch our educational videos and learn more about how GWP ensures weighing result accuracy. Webinars Attend our Measurement Uncertainty & Minimum Weight and Routine Testing of Weighing System interactive GWP webinars to learn more on how to establish and maintain a sustainable quality of weighing processes

9 Good Crystallization Practice Scale-up of crystallization is notoriously complicated and companies are under pressure to develop scalable crystallization processes faster, at lower costs and with higher quality. Companies must control crystallization conditions in order to improve cycle times and optimize product quality. Good Moisture Practice Moisture determinations need to be carried out reliably and quickly so that any interventions in the production process can be made promptly in order to avoid interruptions. Our website offers a valuable Moisture Guide method database and industry solutions which can help to save precious development time. Improving Laboratory Crystallization Focusing on laboratory case studies, key stages in the process development lifecycle where the implementation of FBRM and PVM has been successful are demonstrated. Improving Production Crystallization Discover five high impact ways to achieve ideal crystallization production conditions. Special attention is paid to the most common problem areas encountered in production crystallizations where the implementation of FBRM has proven useful. Crystallization Webinars A variety of on demand crystallization webinars are available on our internet portal. The webinars support you in development, optimization and scale-up of your crystallization processes. Method Database Explore the database that contains more than 100 methods referenced to an official moisture determination method (e.g. drying oven). Industry Solutions Experience complete solutions for moisture analysis in a variety of industries, including sugar, plastics and wastewater. Moisture Measuring Principles Learn more about the method of drying (heating the sample using thermal radiation) and the principle of the switch-off criterion. 9

10 Product News Understand and Control Process Chemistry Challenged by space constraints and/or complex installation requirements? ReactIR 247 is a unique process-hardened FTIR spectrometer designed to fit into nearly any space without sacrificing the proven performance of ReactIR technology. The design of the ReactIR 247 yields an analyzer with high stability and sensitivity in a product format that delivers extreme space savings with plug-in and measure operation. Turn-Key Integrating the Sentinel probe technology to a flow cell permits easy integration into existing flow stream and immediate analysis of the reaction as it occurs. From Lab to Plant Specifically designed for the production environment, ic Process enables the transfer of critical control parameters determined in the lab. Flexibility Flexible sampling arrangements allow for the use of longer probes to reach the fill level for small volume starting conditions. 10

11 Weights for Routine Testing Calibrated With ComparatorPac Balances in regulated environments must be tested regularly with calibrated weights. Weight calibration is an intensive and accurate process, which is likely to become even more important as more industries perform routine test of weighing equipment in order to improve processes, resulting in better quality and reduced cost. ComparatorPac combines a fast, intelligent comparator balance with simple, yet effective, software that eliminates several manual handling steps, resulting in fast, easy and reliable calibrations saving up to 40% on calibration time. Routine weights are back in the lab when needed, avoiding equipment downtimes and paying for more testing weights than necessary. ComparatorPac is the ideal in-house solution for the calibration of OIML Class F2, M1, M2 and M3 weights. The package consists of: 3 comparators for calibrating weights from 1 mg up to 20 kg. OIML F1 calibrated reference weights up to 20 kg. MCLink Software to process calibration data and print reports. One Touch Calibration A simple One Touch starts the calibration process. Simply follow the onscreen instructions and only handle the weights. No more operator or transcription errors as all results are stored and can be sent to any computer. Durable Weights Premium steel, with a high gloss corrosion resistant surface for reliable and durable stability. Calibration Reports MCLink automatically creates calibration reports at a keystroke. All parameters, processes used, references and results, with or without calculations, can be easily printed out in a certificate ready to be signed. 11

12 Spotlight on Promotion Find the Ideal Pipette and Win an Apple ipod Our new pipette finder helps you to find the most efficient and convenient pipetting solution for your application. Try it, request a quote* and enter a competition to win an ipod nano. *No purchase necessary for participation in the drawing Mettler-Toledo AG Laboratory Division Im Langacher CH-8606 Greifensee, Switzerland For more information