Accuracy and Pharmacutical



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Accuracy and Pharmacutical Solution Weighing Team Contents Weighing Errors Weighing Technology Accurate scale with Pharmaceutical Why is accuracy / precision important? Knowing the error of your results helps - To avoid Under/Overfilling - Ensure product and human safety Weighing within defined tolerances all the time - Ensures certain quality standards - Ensures stable production process - Ensures reproducible production Use Qualified Equipment (DQ, IQ, OQ, PQ) - Traceability, Required for GMP Be sure of the quality of your measurement!

What is Resolution The weighing range divided by the display readability gives the scale resolution. A quality scale has a high resolution and is very accurate at the same time. The resolution of a quality scale is certified by Weights & Measures institutes (e.g. PTB). A certified resolution is also called approved resolution and can be used for legal for trade. A high readability automatically results is a high resolution but does not automatically result in high accuracy. This relationship can be affected by different scale technologies. Resolution = Capacity = 150 kg = 15,000d Readability 0.01 kg(d) What does resolution mean to you? You need to consider the resolution of a scale when you are worried about: - Weighing errors - Legal for trade applications 8Resolution need to be approved by Weights & Measure 8Ensures that result has certain accuracy - Stability of displayed weighing result - Ambient conditions 8Wind 8Temperature 8Vibrations How can you technically influence the resolution? 8Scale technology (Stain Gauge / Electromagnetic force compensation) 8Indicator High resolution does not always mean high accuracy Approved Resolution Notified bodies certify scale accuracy related to scale class - Certified resolution is indicated with e (difference between two display steps d following each other Certified or approved scales can only display the e value For legal for trade applications, scales have to be certified in the EU and US. - EU / OIML - US / NTEP 7,583kg Class II e d

Benefits of Approved Resolution Approved resolution e certifies scale accuracy - Confirmed by Weights & Measures Institutes (Notified body) - Approved or certified resolution e is the true value - Displayed resolution d can be anything and does not inform about scale performance Different scale classes indicate scale performance - Typical classes use for industrial weighing applications 8Class II => High precision 8Class III => Medium precision Cap.3 kg Class II 10,000e and 100,000d Readability=3,000g/(10,000e-100,000d) = 0.5g - 0.05g Display value d is just a dummy value Typical Certifiable Resolution of Scales Class II scales can have different certifiable resolution ranges - From 5000e up to 60000e (Single range, delta range, e=10d) - Typically within a temperature range of 0-40 C Class III scales can have different certifiable resolution ranges - Standard: 1x3000e (e.g. 30 kg scale => 0-30kg / 10g, e=d) - 2x3000e Multi-Range (e.g. 30kg scale => 0-15kg / 5g, 15-30kg / 10g ) - 2x3000e Multi-Interval (e.g. 30kg scale => 0-15kg / 5g, 15-30kg / 10g ) - 3x3000e Multi-Range/Multi-Interval) - 1x7500e (e.g. 30kg scale => 0-30kg / 5g, e=d) - Typically within a temperature range of -10 to 40 C Precision scales ensure high resolution within large temperaure range Typical Errors according OIML MPE Chart OIML states maximum allowed error

What is precision? The degree of agreement between repeated measurements of the same quantity. The numeric value of precision is normally expressed as the result of the calculation of the standard deviation. Precision can also be expressed as repeatability (reproducibility). Precision depends only on the size of the differences observed while repeatedly weighing the same object and it is not concerned with freedom from error of the final result. What does precision mean to you? You need to consider the precision of a scale when you are worried about: - Reproducible and stable production - Ensure similar batch quality - Major influence of weighing tolerances of low quantities on big scales - Same weighing result regardless on what area of the scale the product is placed 8Reducing operating errors - How can you technically influence precision? 8Scale technology (Stain Gauge / Electromagnetic force compensation) 8Direct force weighing technology / Lever weighing system High precision does not always mean high accuracy What is corner load error? Cornerload refers to the ability of an instrument to deliver the same weight reading for a given object anywhere on the weighing pan. Scale technology has a major influence to corner load errors. Scales with mechanical lever system have much lower corner load erros. 1 2 3 4 5

What is Linearity Error? Linearity refers to the quality of delivering identical sensitivity throughout the weighing capacity of a balance or scale. Test this characteristic by weighing two stable objects separately, each of approximately one half the weighing capacity. The sum of the two readings should equal the reading obtained when both objects are weighed together. What is Hysteresis error? Property of load cells, and other weighing systems dependant on elastic materials, such as spring balances, resulting in a different indication at the same load, depending upon the direction of approach to that load, i.e. whether it is approached by increasing the load or decreasing the load. 1 2 3 4 5 What is Accuracy? The degree of agreement between the result of a measurement and the true value of the quantity measured. The sum of all individual scale errors are relevant for the accuracy of a scale and therefore also for its weighing certainty. Corresponding to the international guidelines of the EC and the OIML, there are different classes of scale in order of increasing accuracy defined in the EC directive 90/384: - Class I Special (e.g. high precision balance) - Class II High (e.g. high precision industrial scale) - Class III Medium (commercial scale) - Class IIII Ordinary (e.g. high capacity scale)

What does accuracy mean for you? You need to consider the accuracy of a scale when you are worried about: - Over/Underfill of product - Product safety - Minimizing operating errors - Weighing Speed - Weighing of light and heavy products on same scale - Changing ambient temperatures - Quality of your weighing in general Accuracy is defined by scale and sensor technology Contents Weighing Errors Weighing Technology Accurate scale with Pharmaceutical Sensor Technology Strain Gauge technology - A metallic or semiconductor material of small cross sectional area that is bonded to a surface and elongates or contracts with that surface. This deformation results in a change in its electrical resistance, providing means for subsequent measurement. - Used for most electronical scales (e.g. bathroom-, kitchen, supermarket- and industrial scales) Cheap technology for mass production

Strain Gauge Benefits Economical sensor with acceptable accuracy - Typically 3000e-7500e resolution Large range of capacities form gram to several tons Rugged and robust Flexible use for many different scale types Easy to service Due to analog interface universal connection to terminals Cheap technology for mass production Sensor Technology Electromagnetic Force Compensation (Monobloc) - The principle of EMFC is based on the electrodynamicconversion principle. The Monobloc consits of a high-strength aluminium alloy. A complex pattern is eroded out of the compact block. Weigh scale sensors based on the EMFR principle are typically 10 1000 times more accurate than strain-gauge-based industrial load cells and other devices based on the measurement of deformation. High quality technology for high precision weighing Monobloc Benefits High precision sensor with high accuracy - Up to 60000e approved resolution Internal calibration - Ensures scale performance - Required for GMP Digital communication - Easy maintenance due to plug & play scale-terminal connection - Weight is generated in weighing cell 8Less electical noise disturbance during data transmission Excellent technology for high precision weighing

Scale Technology In addition to the weighing sensor, the scale construction has a major influence to the scale accuracy. - Precision / Repeatability - Linearity - Corner Load errors - Stabilization time - Hysteresis Depending on the application various scale constuctions can be used. - Single point direct force construction (e.g. bench scales) - 4-point direct force construction (e.g. large industrial floor scales) - Single point lever force construction (high precision scales) Mettler Toledo uses all construction types Scale Technology Single Point Single point direct force construction - Used with bench scales up to 600kg - Standard accuracy type scales (Strain Gauge) - High precision scales (Monobloc) - 1 loadcell per scale - Capacity of loadcell is more or less similar to scale capacity Strain Gauge Loadcell Monobloc Loadcell Mettler Toledo uses all construction types Benefits Single Point Scales Main application: bench and portable Large variation of different scales - Sizes - Capacities (typically 3-600kg) - Material (painted, galvanised, stainless steel) - Different resolutions / Accuracy - From IP44 to IP69k - Hygienic designs Simple design ensures easy service Used in all type of industries Analog and digital versions BBA425 PBA330 BBA449-A15 PBA430-B60 Most frequently used scales for bench applications

Scale Technology 4 Point 4 point direct force construction - Used with floor scales - Standard accuracy type scales (Strain Gauge) - Sum of all loadcell capacities is higher than scale capacity (preload possible) - Typically 4 loadcell per scale Mettler Toledo uses all construction types Benefits 4 point scales Main application: Floor scales Large variation of different scales - Sizes - Capacities (typically from 150-6000kg) - Material (painted, galvanised, stainless steel) - Different resolutions / Accuracy - From IP65 to IP68 - Hygienic designs Simple design ensures easy service Used in all type of industries Analog and digital versions PUA579 PTA455 DNE sk with raisable stainless steel load plate PFA574 Most frequently used for floor scale applications Scale Technology Lever System Single point lever construction - Used with bench and floor scales - High precision accuracy (Digital strain gauge + Monobloc) - Capacity of scale depends on lever system - 1 loadcell per scale - 2 loadcell capacities (15 and 32kg) for complete weighing range from 15 kg 3 tons 1.5 ton scale 15 kg loadcell Levers Perfect technology for high precision applications

Benefits Lever Based Scales Main application: Bench, portable and floor Large variation of different scales - Sizes - Capacities (from 15-6000 kg) - Material (painted, galvanised, stainless steel) - High readability (up to 3.2 Mio points) - Excellent precision and accuracy - High IP ratings - GMP Digital version - Plug & Play installation (terminal/scale) - Change of scale / terminal without recalibration KA / MA15s KCC / MCC 150 / 300s Used in all type of industries KE/ME 3000 with raisable loadplate Excellent scales where accuracy is important Comparision Bench Scales Mobobloc technology is > 10 times more accurate Comparision Floor Scales Mobobloc technology is > 10 times more accurate

Contents Weighing Errors Weighing Technology Accurate scale with Pharmaceutical Accuracy scale to Pharma process 1. API Synthesis 2. Dispensing 3. Mixing 4. Tableting 5. Packaging Courtesy Roche Dispensing: Where exact amounts count 1. API Synthesis 2. Dispensing 3. Mixing 4. Tableting 5. Packaging Raw material identification Raw material weighing High Resolution digital scales Precision balances XP Line Analog scales Weighing indicators IND449, IND690, ID30 Formulation solutions Courtesy Roche

Weighing in the dispensing room FormWeigh.Net application running on ID30 with connection of any three weighing systems Portable scale either with indicator or hooked-up to the IND690/ 690xx or ID30 Weighing indicator IND690/690xx Floor scale hooked-up to the IND690/ 690xx or ID30 Bench scale hooked-up to the IND690/ 690xx or ID30 Weighing in the dispensing room Wireless data exchange over Bluetooth or WLAN Wired data exchange over CL, RS232, Profibus DP or Ethernet IND690 Printer Barcode scanner for product identification Weighing station #1 Weighing station #2 Weighing station #3 Product identification with RFID technology High resolution portable scale KA 15kg/0.1g High resolution bench scale KCC 150kg/1g Easy to clean floor scale PUA579 600kg/100g Mixing and granulation 1. API Synthesis 2. Dispensing 3. Mixing 4. Tableting 5. Packaging Granulates / Pellets making Sieving and Drying Mixing of API with excipients Formulation solutions Weigh modules for reactors, tanks, mobile vessels Courtesy Roche

For accurate weighing and material transfer Converters and indicators IND130 - IND130 - IND560 Platforms - Full range of K-line high resolution platforms - Full range of analog platforms Weigh modules - Ultramount - Ringmount - Flexmount IND560 KES1500 Flexmount Ringmount Ultramount Packaging solutions 1. API Synthesis 2. Dispensing 3. Mixing 4. Tableting 5. Packaging Packaging, bottling Final product inspection Checkweigers Metal metectors and X-ray systems Courtesy Roche End. End.