Engineering Manufacturing Installation Process equipment for production scale in chemistry and pharma

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Engineering Manufacturing Installation Process equipment for production scale in chemistry and pharma Compact, customized solutions Complete process units Robust material and design Reliable and safe operation Applications Reaction Evaporation Vacuum distillation / reflux Azeotropic distillation Rectification Absorption BÜCHI THE WAY TO GET RESULTS!

Büchi AG Process equipment with tradition Büchi AG is a globally leading manufacturer of process equipment for the chemical and pharmaceutical industry. Company history: 1946: founded by the brothers Jakob and Hermann Büchi Sr. in Uster, Switzerland 1949: development of flexible glass connection system, break-through as plant manufacturer for chemical production in Switzerland 1979: development of chemreactors for upscaling and small scale production in pilot plants and kilolabs 1980: development of pressure reactor systems in glass and metal for laboratory and pilot plants 1981: start export business Büchi AG today: worldwide sales network, local service organizations chemical process equipment in glass-, glass lined steel for chemical and pharmaceutical industry (from design to installation) glass plants from laboratory to production scale pressure reactors for laboratory and small-scale production continuous innovation leading to up-to-date technology Technology and know-how Production plants for (fine-) chemicals and pharmaceuticals require stringent standards regarding corrosion resistance. Easy, fast and efficient cleaning is of great importance. These requirements are met by using borosilicate glass, glass lined steel vessels and PTFE (sealing material). These materials offer: excellent chemical resistance, particularly to strong acids smooth, nonpouros surfaces physiological safety, inert behaviour easy process supervision and improvement due to transparency of glass Glass plants with flexible «büchiflex» glass connection The complete system with «büchiflex» glass components from DN15 DN600 guarantees fast deliveries from stock. The «büchiflex» connection features: tightness, pressure- and vacuum stability operational safety and functionality mechanical stress-free, easy and time saving installation and maintenance remains flexible during operation Planning efficient, custom tailored, clear We use modern 3D technology for plant design. This allows time saving data transfer during the design phase and generates clear and understandable plant drawings. By using as many standard components as possible we can reduce the total lead time for entire plants or spare parts to a minimum. In general a complete plant consists of a glass lined, agitated reactor vessel (from various suppliers) and a glass overhead with feed vessel, condensers, phase separator and receiver tanks. Innovation, approvals, certificates CE declarations of conformity (PED/ATEX) as well as declarations on FDA conformity are part of the documentation to validate our equipment for cgmp applications. 2002: ATEX / PED 2004: new flame-polished büchiflex glass connection 2009: development of filter systems 2012: TA Luft approval for büchiflex connection 3D engineering of complete plants büchiflex unique flexible glass connection: safe, clean, economic (DN15-DN600) 2

LSA I-32 TI I-9 V-41 P-60 P-59 V-25 V-26 P-58 H/K out H/K in I-11 TI I-10 V-44 P-62 P-64 HZ I-12 TI I-4 I-34 PSD-1 P-18 P-30 P-27 P-25 V-12 P-68 V-38 V-39 FI I-19 I-20 N2 PSD-2 P-11 V-20 V-21 HZ I-41 I-35 P-23 M V-24 V-34 V-37 V-36 FI I-17 I-18 V-33 N2 V-23 V-32 V-31 PSD-5 I-8 I-6 TIC LUX I-26 S-11 V-3 HSZ+- I-22 TI I-5 TI I-36 I-27 TI I-37 HZ I-24 M E-10 P-2 H/K OUT H/K IN P-8 ph QI I-3 N2 P-6 V-15 V-2 V-14 V-1 XI I-2 V-16 P-42 V-17 HZ I-25 M P-43 PSD-3 P-41 P- HE-4 HE-1 HE-2 HE-3 T-3 PS-1 P-32 VT-2 VT-1 P-58 E-11 FI I-31 S-7 I-14 N2 I-28 P-48 V-29 V-30 N2 KW out P-57 P-1 I-21 E-12 Probenahme V-43-1 -5 P-63 T-1 T-2 R-01 M E-6 E-4 E-2 D flow chart Glass tubing / piping easy and safe due to flexible glass connection 3

Components Heat exchangers Spiral condensers Shell and tube condensers Depending on the plant size and the type of process as well as a result of the required heat exchange area, different types of condensers are used: spiral condensers for production reactors up to 630 liters feature efficient cleaning shell and tube condensers with heat exchange areas of up to 23m 2 are used for large reactors they are available with inner tubes in borosilicate glass, silicon carbide (SiC) or Hastelloy and with optional safety chamber. Glass-spiral condensers in parallel configuration Universal chemical resistance All Büchi condensers are suitable for long-term operation as condensers or after coolers for highly corrosive medias and therefore perfectly comply with the operation conditions in multi-purpose plants. Shell and tube heat exchanger with glass tubes (without safety chamber) Shell and tube heat exchanger with SiC tubes with safety chamber Packed Columns for distillation / rectification Columns up to DN 600 are available. They can be packed with random packings such as Raschig rings, ceramic saddles, PFA packing elements or structured packings dependent on the required separation performance and process media. Stainless steel Hastelloy Ceramic Pall rings 4

SiC shell and tube type heat exchangers Silicon carbide (SiC) shell and tube type heat exchangers in sizes up to 23m 2 feature outstanding heat transfer, which results in very compact process plant constructions and reduces operation costs. SiC inner tubes outstanding thermal conductivity excellent corrosion and abrasion resistance superior thermal shock and pressure resistance FDA approval, for cgmp manufacturing easy to clean Safety chamber The safety chamber adds an additional separation between the cooling media and the process side. This enables increased operation pressure of the cooling fluid. Safety flange Stainless steel Endplate PTFE Gasket Utility side Process side Outlet Safety chamber Saddle packing Raschig rings Solvent recovery, packed DN300 column, reflux condenser and controlled reflux divider 5

Design Calculation Engineering Because of often encountered space restrictions and challenging processes a thorough layout plan, including design calculations of the apparatus, is required within the scope of the overall project design. The plant has to be optimally intergrated. Functionality, operator and maintenance access, and other factors must be taken into consideration. Project planning Our competent project engineers as well as sophisticated planning tools help to design the plants according to customer requirements in a timely fashion. Calculations Büchi uses software tools that support the calculation of all apparatus during the planning stage. Heating/cooling power, stirrer power, mixing characteristics and other reactor parameters can be calculated. On our website we offer programs for calculating pressure drop and condensation power or cooling power for shell-and-tube condensers, spiral-tube condensers and product coolers. Engineering Example of pressure drop and separation efficiency of a packing for columns Manufacturing Installation Many years of experience, continuing skills development, and the professionalism of our staff allow us to provide high-quality workmanship and excellent products. Our glass blowing department and mechanical workshop process corrosion resistant materials every day. Our installation teams are talented, reliable, and competent; they are accustomed to work all over the world. Thorough planning and the use of the «büchiflex» connection help them perform the installation and service process fast and precisely. Documentation validation maintenance The documentation supplied along with the product meets the requirements of the pharmaceutical industry and provides all required information related to performance, operation, safety and maintenance. Glass blowing department Mechanical production Montage 6

Classification of vessels acc. Directive 97/23 /EU Pressure equipment directive PED 3D-CAD Planning Catalog of DN15 DN600 buchiflex glass components / spare parts Documentation / Certification 7

Processes Reaction, stirring, mixing Glass lined reactors (DIN-reactors AE or BE) are suitable for a variety of processes such as chemical reactions (atmospheric or under pressure), gas dispersion, mixing of liquids/solids, crystallization and heating/cooling. Extractions and phase separations can also be performed with the proper fittings on the bottom discharge valve. Büchi supplies complete systems with glass lined reactors from various suppliers. Fittings and instrumentation on the reactor are also included as well as distributors and collectors. Distillation A stirred reactor commonly serves as reboiler. Vapors ascend to the condenser via the vapor line and the condensate either descends back into the reactor or passes into the receivers. The number of «büchiflex» spiraltube condensers or shell-and-tube condensers with borosilicate glass, SiC or Hastelloy tubes required depend on the process and size of the plant. Azeotropic distillation The condensate mixture exiting the condenser is continuously separated in the phase separator (provided the phases are immiscible). One phase returns to the reactor while the other proceeds to the receivers. The size of the plant determines whether vertical or horizontal phase separators are employed. Rectification Rectification columns in sizes up to DN600 with a wide range of random packings or with structured packings dependent on the required separation performance and corrosion restistance can be supplied. The reflux ratio is controlled by various configurations of appropriate valves. Condensation takes place in a spiral condensers or shell and tube type heat exchangers with borosilicate glass, SiC or Hastelloy tubes. Absorption Non-condensable vapors and gases can be removed from off-gases in scrubbers. In the presence of strong acids, absorbtion columns made of borosilicate glass with nonmetallic random or structured packing are recommended. Multiple columns with various absorption liquids and corresponding piping with valves are used depending on the vapors and gases in question. Other apparatus / processes circulation reboilers falling-film evaporators (mobile) mixing vessels mobile transport vessels separator vessels glass piping (waste water, exhaust, transfer) High performance SiC silicon carbide heat exchanger Horizontal and vertical phase separator 8

Gas scrubber Falling-film evaporator 9

Examples cgmp facility with 800 litre glass lined AE / BE reactors, distillation glass overhead with SiC condensers and glass lined receiver tanks for A production 4000 litre BE reactor with coated glass upper section DN300 vapor line with protective glass coating 10

Distillation overhead with SiC shell and tube heat exchangers 1000 litre cryogenic reactor with glass upper section DN400 liquid / liquid extraction column, capacity 800kg/h 11

Standard configurations diekonkreten.ch 08/14 Reactor eat ex- Spiral Tubular Tubular Secondary Feed Receivers Phase Vapor DIN change area condenser Heat exchanger Heat exchanger condenser vessel seperator duct AE/BE m 2 m 2 Glas m 2 SiC m 2 m 2 l l l DN 100 0.85 2.6 (2x1.3) - - 0.6 50 2x50 1 70 160 1.25 3.9 (3x1.3) - - 1.0 50 2x50 1 70 250 1.65 4.8 (3x1.6) - - 1.3 100 2x100 3 100 400 2.45 7.8 (6x1.3) - - 1.3 150 2x200 150 630 3.1 9.3 (6x1.6) - 3.2 1.6 200 2x200 200 1000 4.6-12.5 4.0 1.6 500 2x200 200 1600 7.35-16.0 5.0 1.6 500 2x500 200 2500 9.6-20.0 6.5 1.6 *G/L *G/L 300 4000 13.5-23.0 8.0 1.6 *G/L *G/L 100 300 *G/L (glass lined steel) The table above is only an example Büchi process equipment from laboratory to production scale «minipilot» «chemreactor» «Production» Lab-scale 5 15 litre Pilot-scale 15 250 litre Production-scale 100 10000 litre Büchi AG Phone +41 (0) 44 905 51 11 Gschwaderstrasse 12 Fax +41 (0) 44 905 51 22 CH-8610 Uster/ Switzerland www.buchiglas.com 40.9P212.B010