Containment Technology
Containment Technologyfor Solid Dosage Processing
2·CONTAINMENT TECHNOLOGY
CONTAINMENT TECHNOLOGY·3UnderstandingContainmentContainment is an issue in 9 out of 10cases of solid dosage form production.Containment issues have become a vitally importantContainment Expertsaspect of solid dosage form production. ActiveGEA has a long history of expertise in the fieldpharmaceutical ingredients (APIs) are becomingof containment. The company not only offers aevermore effective, with more than 50% of all newcomprehensive range of robust and compliantchemical entities (NCEs) being classified as potentcontainment products, it also boasts unrivalled(OEL 10 μg/m3); at the same time, the health andexperience in identifying the most appropriateprotection of operators, all over the world, is beingsolution and a thorough understanding ofput under an increasingly intense spotlight.containment risk analysis. We don’t just know aboutcontainment, we live and breathe it!In addition, navigating the maze of availablehardware components and the huge variety ofBUCK Technology and SMEPACcontainment solutions has made it more and moreGEA was fundamentally involved and worked withdifficult to select the most appropriate equipmentan international working group to create a guidefor the specified task: suppliers of various hardwareto containment testing. Now published by thecomponents have developed a huge variety ofInternational Society for Pharmaceutical Engineeringcontainment solutions, making it difficult, even(ISPE) and known as SMEPAC (Standardizedfor experienced people, to decide on the optimalMeasurement of Equipment Particulate Airbornesolution.Concentration), this guide defines the test processesand parameters needed to assess the different levelsof containment required throughout a plant.Keeping the real operating conditions of the finalinstallation in mind, GEA can determine what levelof containment is required where, optimizing themanufacturing process and making it efficient, safeand cost-effective.
4·CONTAINMENT TECHNOLOGYWhat level of containmentdo I need?GEA Design for ContainmentThe production of oncology drugs, hormonal products and/orAdditional features such as removable hoppers andother highly potent compounds requires particular attention:supplementary extraction provide increased safety for operatorsit is essential to avoid exposure of the operators to the drugand facilitate cleaning. Solutions range from single-level, simpleas well as prevent the cross-contamination of other productsapplication solutions to multiple-level, integrated dispensarymanufactured in the same facility.management systems. Bulk ingredient dispensing includes fullyautomated excipient dosing or interfacing with bulk ingredientsContained Materials Handling Expertisefor high containment. Active pharmaceutical ingredients (APIs)GEA specializes in contained materials handling solutionscan be dispensed into a contained charge vessel, which can thenfor primary and secondary pharmaceuticals and healthcarebe safely transported to the point of use within the plant.companies. With BUCK high containment split butterfly valves,we offer a wide range of technologies and equipment thatIBC Blendingimprove and enhance the efficiency and performance of solidFlexible blending solutionsdosage form plants for the safe transfer of powders. We knowContainer blending as part of an intermediate bulk containerwhat level of containment is needed where.(IBC) system has long been established as the most efficientmethod of mixing granules and powders in pharmaceuticalWith a long-established pedigree of expertise andmanufacturing. R&D, small-scale and full-scale pharmaceuticalimplementation, GEA equipment and technologies meet the veryproduction blenders enable contained process technologystringent demands of production performance, plant and markettransfer during scale-up, minimizing process validation activity.flexibility (single and multi-product) and, of course, value. Withworldwide experience and market-leading credentials, we haveThis is fully supported by GEA’s detailed research programdeveloped an outstanding reputation for quality and service toand testing facilities. Hoist- and pedestal-mounted versionsbecome the leader in contained materials handling.are available, as well as through-the-wall designs that offersignificant room layout benefits.Dispensary Handling Expertise and ManagementOur modular dispensing solutions ensure simple, ergonomicVibroflow operation and consistent flow whilst effectively controlling thePrevents product segregationdispensing process. The control system integrates the processVibroflow technology allows IBCs to discharge poorlywith the recipe management system to provide batch dataflowing product in a reliable and repeatable manner. Withsecurity and traceability for validation purposes.product containment and operator safety being of paramountimportance, it is no longer acceptable for operators to interveneand open the IBC to remove blockages. Vibroflow is a provendischarge technology that has been thoroughly tested by leadingpharmaceutical manufacturers and installed successfully in anumber of primary and secondary API plants.
CONTAINMENT TECHNOLOGY·5CASE STUDY:Containment ProjectDirect Compression of Hormonal TabletsWishing to maximize the solid dosage production ofa highly potent hormonal product, a leading drugmanufacturer tasked GEA with significantly increasingtheir output, providing a safer and more efficient factoryenvironment and introducing new systems that wouldreplace the existing isolator-based process.The challenge for GEA was to use their product flow andcontainment expertise to remove as much isolator-basedprocessing as possible, making the production flowmore efficient, whilst maintaining the high levels ofcontainment and operator safety required. Another keyfactor was maintaining blend homogeneity.GEA first demonstrated a patented high containmentsystem, the MODUL S rotary tablet press with aWash-off-Line (WOL) Exchangeable CompressionModule (ECM). GEA also demonstrated the use of multitip tooling: using two tips per punch (station) doubledthe tablet press output. A specially designed feeder anddedicated software ensure optimal output.GEA then demonstrated their ability to successfullyblend the low levels of API with poorly flowingexcipients. This was achieved using the company’sblending Prism technology, a very effective aid to thebin-blending process.The new system was fast tracked; the preliminarydetails were agreed within 4 months and the equipmentwas delivered less than one year after contract signing.Removing much of the isolator-based processing andexpanding into the new factory space has enabled asignificant increase in both batch size and yield, andimproved the overall working environment.
6·CONTAINMENT TECHNOLOGYHow do I optimize the granulation process,and ensure both product and operator safety?Feeding the Granulation ProcessIntegration by DesignProcess flow interfaces for the granulation areaDrawing on its world-class expertise and technologies, GEAThe effective and safe transfer of both excipients and activeoffers an entire range of state-of-the-art process equipmentingredients is essential. A number of options are available:that has been designed and built with system integration inmind. A modular approach allows customers to select standardGravity feeding: Gravity loading through a discharge stationprocess modules to suit project needs: fully integrated turnkeyfrom above or via a post hoist are ideal solutions, ensuringinstallations can be supplied, including fluid bed processcontainment and simplicity of cleaning. API discharge vesselsequipment combined with top- and bottom-drive high shearcan be used to deliver more potent formulations directly into themixer-granulators with integrated contained materials handling,granulator.wet and dry milling facilities, product handling systems,binder and coating preparation units, filtration units and tabletVacuum feeding: When room height is a limiting factor,compression.a contained vacuum station can be used: incorporatingcontainment valves that improve airborne dust levels, they canSafety, containment, product flow and building requirements arehelp to reduce area classification categories. Safety levels canin-built for full integration and optimum process efficiency. Ouralso be improved by combining interlocking containment valvesservice includes design, installation assistance, commissioningwith a nitrogen purge system.and process validation, as well as training and technical support.Installation, operation qualification and documentation are doneUnloading granulation equipment: Inline sieving or millingaccording to FDA/GAMP guidelines.before the granules are loaded into a container can facilitate theprocess. A lubricant or other materials can then be added (oftenSystem Integrationdone using charge containers or Hicoflex bags) and blendedOur distinctive specialization lies in the integration of thewith the granules.GEA containment technology into complete solutions for pharmaceutical solid dosage form facilities. With an emphasisGranulationon quality and GMP standards, we are committed to workingDesigned for integrated containmenttogether with our customers to deliver custom-built, first classGEA specializes in the design and manufacture of fluid bed andsolutions for projects of all sizes and complexity.high-shear granulation technology and is uniquely qualified toprovide integrated, state-of-the-art high shear mixer-granulatorSafety and the Environmentand fluid bed drying solutions.For full compliance with national, local and in-house regulations,GEA offers a range of emission control options includingA modular approach means that customers can select standardsolvent recovery systems, outlet filters and full containmentprocess modules to suit their project needs. Fluid bed dryers andplants. Equipment can be supplied to meet explosion-proof andcoaters can be combined with high shear mixer-granulators, wetpressure shock standards as required.and dry milling facilities, product handling systems, binder andcoating preparation units, and filtration units, all of which haveEnd-Point Detectionbeen designed for use in fully contained integrated systems.The FDA’s PAT (Process Analytical Technology) initiative hasSafety, product flow and building requirements are built in forenabled GEA to combine its equipment design skills and processfull integration and optimal process efficiency.engineering know-how to integrate online (PAT) analyzersinto its systems in a way that can provide real insight into theoperation of the process and help customers to achieve keyproduct quality targets.
CONTAINMENT TECHNOLOGY·7CASE STUDY: Penn PharmaFully integrated, high-containment, contract drugdevelopment and manufacturingAfter conducting extensive market research, PennPharma identified an increased need in the solid doseoncology market for the outsourced development andproduction of highly toxic drugs. Its production site hadbeen manufacturing potent solid dosage products formore than 20 years but needed additional capacity.Penn Pharma elected to work with GEA because of itsproven track record in containment technology andexpertise in creating fully integrated production lines.GEA’s approach was to eliminate the use of isolation suitsin favor of containment interfaces (BUCK MC valvesand Hicoflex ).The new plant now includes the first commercialPharmaConnect “through the wall” system in Europe.The contained R&D line for wet granulation alsoincludes the dispensing of excipients and potentpowders, GEA’s PMA 150 and FlexStream 1000 forgranulation and drying, dry milling, granule collectionand blending, tablet compression using a MODUL Ptablet press with a Wash-off-Line ECM (ExchangeableCompression Module) and pellet coating.The plant also has a contained R&D line for directcompression and a separate production line that offerscontainment interfaces for powders, API and excipientdispensing, dry milling and powder collection and blending.Penn Pharma is now a single source for the developmentand production of highly toxic drugs at one of the world’smost advanced and efficient plants. The project hassignificantly increased their capacity and the companycan now manufacture approximately 500 additionalbatches during a standard two-shift operation.
8·CONTAINMENT TECHNOLOGYHow do I eliminate producttransfers during granulation?By definition, a single-pot process is contained, making it theThe UltimaPro -HC is equipped with containment tools forfirst choice for the granulation of highly potent compounds.loading and discharging (Hicoflex , MC valves, etc.); a full,No transfers are required between process steps, except tovalidatable CIP system; contained sampling options or PAT forload the raw materials and unload the dry granules (usingend-point determination; and an optimized vacuum system withBUCK high containment split-valve technology). This notHEPA filtration. Vacuum drying is the basic drying technologyonly protects the operators from exposure to potent products,with the option of adding microwaves to increase yields byit also protects the products from external factors such asoptimizing the process parameters, reducing wet lumps andheat, light and moisture. Specific solutions are available forsticking. product loading and discharging to achieve the desired levelof containment for the whole process.Using proven standard components, GEA can supply bothsimplicity and flexibility in plant design. User-selected processSingle-Pot Processingoptions, control systems and liquid recovery units combineWhether the customer’s requirement is for mixing, granulatingin a system that meets your process requirements exactly.or drying, GEA has a solution for every processing challenge.This approach ensures that qualification and validation workThe UltimaPro single pot (or one pot) technology offerscan be kept to a minimum and ensures successful results. Asa choice of mixing, granulating and drying options that aredemonstrated in the case study, for example, we have a leadingintegrated into a single processing vessel. With our help, thisposition and a proven track record as a system integrator forallows the customer to choose the most appropriate techniquehigh containment projects with single pot technology forfor the product.oncology and hormone applications.With high-shear granulation technology at its core, single potCleaning and Maintenanceprocessing relies on the application of a vacuum within theProcess optimization depends on efficient, effective cleaning.bowl to dry the wet mass. This technique allows pharmaceuticalAutomation of the cleaning process ensures repeatability, allowscompounds to be dried at very low temperatures and, even ifvalidation and minimizes downtime. In recognition of theorganic solvents are used during the granulation process, anfundamental role played in today’s advanced powder processingefficient solvent recovery systems means that environmentalindustry by automated clean-in-place procedures, GEA hasexhaust levels are minimal.developed a unique approach to CIP. The integrated designensures that all lines and hoses for the utilities of the plantKey Characteristics(water, electricity, hydraulics, etc.) are concealed. This creates aSingle pot processing is an extremely flexible technology;safe and uncluttered working space.with its various processing options, it’s ideal for manydifferent applications and products. Whether for standardCIP and WIP systems: More efficient cleaning is one of the keywet granulation, melt granulation, pelletizing or effervescentadvantages of system integration. We provide validated cleaningproduction, and/or combined with vacuum or microwave drying,with minimal downtime. GEA offers CIP-by-design (patented)a single pot processor can achieve the required result.features in all of its systems. Every aspect of the integrated plant,from inlet to discharge, has been value-engineered for optimumThe swinging bowl option enhances this flexibility even furthercleanability. Spray systems, tank cleaners, nozzles and seals areby being able to process older formulations to a high qualityan integral part of our equipment design. Every plant deliveredstandard. Quick product changeover is simple and efficient, andby GEA has a tailor-made WIP or CIP system that suits yourthe equipment is easy to clean as a result of the clean-in-placeprocess.(CIP) system.
CONTAINMENT TECHNOLOGY·9CASE STUDY: Ranbaxy Laboratories LtdTop-end containment line for anticancer drugsGEA supplied a complete containment line to Ranbaxy Laboratories Limited(Gurgaon, India) to manufacture highly potent anticancer drugs with an OEL of1–10 μg/m3. It was essential that the process prevented any cross-contaminationin the production area and limited operator Real Daily Intake (RDI) ofhazardous substances to well within the Acceptable Daily Intake (ADI).During the selection process, several key equipment features were specified: all units had to provide full containment the entire process had to be contained in a single machine to avoidcontamination and limit material handling the technology had to be flexible enough to adapt to different products andbatch sizes the process should provide maximum yields with minimum wastage there should be a clear and straightforward documentation procedure.In addition, it was essential that the operators had an in-depth understandingof both the equipment and the relevant containment issues.To meet their production, containment and whole-life cost requirements,Ranbaxy chose two single pot processors from GEA: the UltimaPro 10and the UltimaPro 75 (10 L and 75 L processing bowl, respectively).The safe, low temperature, vacuum drying technology was augmentedwith microwaves or Transflo (gas-assisted vacuum drying); end-pointdetermination was achieved using a torque sensor (granulation) and NIR(end humidity); a built-in camera allowed operators to view the processwithout opening the lid; and cleaning was done by a comprehensive fullyvalidatable CIP system.The new equipment has allowed the company to develop niche oncologyproducts in a contained environment that protects its workforce and thewider environment from toxic compounds. Since installation, predictedlevels of production, containment and operational efficiency have beenachieved. In addition, factors such as very effective microwave dryingfor aqueous feeds, more consistent granule sizes and much less operatorintervention than had been anticipated have been cited as “areas ofexceptional performance.”Lalit Sood, Projects Director for Ranbaxy, said: “The unit cost reductionhas opened up the market and enabled the company to provide a hardto-resist proposition worldwide. The GEA technology gives us security ofoutcome with the guaranteed quality and consistency we need.”
10·CONTAINMENT TECHNOLOGYCan I improve tablet press changeover times,even when compressing potent actives?When dealing with highly potent substances, owing to theand cleaning is done away from the tablet press area, allowingcomplex geometry of tablet presses, compression is the mostthe machine to do what it has to do — make tablets.challenging stage of the tablet manufacturing process. AllGEA MODUL tablet presses are based on the company’sProviding both operator and product safety, the ECM can beExchangeable Compression Module (ECM) concept.easily removed and exchanged with a replacement unit in just30 minutes for fast product changeover. This is the only conceptContained Compressionthat combines containment with productivity. Whereas, in theThe Exchangeable Compression Module (ECM) is the uniquepast, tablet presses were out of operation for 8–12 hours forand distinctive feature that sets the GEA MODUL tablet presscleaning (manual or wash-in-place), GEA’s ECM technologyapart. The patented ECM is a tremendous
BUCK high containment split-valve technology). This not only protects the operators from exposure to potent products, it also protects the products from external factors such as heat, light and moisture. Specific solutions are available for product loading and discharging to achieve the desired level of containment for the whole process.
DIRECT-PLUMBED Containment Tanks Models 2478SQ-NA-DP 1100Lb/150Gal Containment Tank 3072-NA-DP 1500Lb/200Gal Containment Tank 4280-NA-DP 2650Lb/353Gal Containment Tank. About this manual Read this manual for the following information about inside Direct-Plumbed containment tanks:
Single Storage Tank Containment Wall Height Calculation 61 . 3. Example Multiple Storage Tank Containment Wall Height. Calculations 63 . 4. Multiple Storage Tank Containment Wall Height Calculations 64 . D. Bulk Facility Containment Construction Criteria 66 . 1. Outline of General Specifications for cast concrete secondary. containment systems .
Cost Containment in Healthcare September 2015 2 Cost Containment in Healthcare September, 2015 3 DEFINITION & CLASSIFICATION What is a Cost Containment? v Almost all European countries have introduced and implemented cost containment measures that keep expenses in check.
Pennsylvania Health Care Cost Containment Council (28 PA Code CH. 911 and 912) Severity Methodology The Pennsylvania Health Care Cost Containment Council, under the authority of section 5(b) of the Pennsylvania Health Care Cost Containment Act (35 P.S. §449.5), is submitting final-form regulations toFile Size: 474KB
6.2-21 Single Failure Analysis-Containment Vessel Heat Removal Systems 6.2-117 6.2-22 Containment Shell External Surface Temperature (Annulus Air Temperature 85 F) 6.2-120 6.2-23 Containment Vessel Isolation Valve Arrangements 6.2-121 . 6.2-29 Significant Containment Metals and Paints Subject to Corrosion by Spray Solutions 6.2-141
Secondary Containment for Mobile/Portable Containers rMobile and portable bulk containers must comply to the specific sized secondary containment requirements of 40 CFR 112.8(c)(11) Must be positioned or located to prevent a discharge to navigable waters Secondary conSecondary containment must be sized to contain tainment must be sized to contain
The task force will focus on well control and containment procedures including well shut in, kill methods, subsea capping, and collection & processing methods. This task force has initially identified 5 key areas of focus for Gulf of Mexico deepwater operations, the Focus Areas: well containment at the seafloor; intervention and containment
Andreas Wagner. ERAD 2014 - THE EIGHTH EUROPEAN CONFERENCE ON RADAR IN METEOROLOGY AND HYDROLOGY ERAD 2014 Abstract ID 306 2 Using a pattern recognition scheme, single pixels or groups of pixels that show unusual signatures compared to precipitation echoes, are identified in these accumulation products. Such signatures may be straight edges, high gradients or systematic over- or .
