PHARMACEUTICAL INDUSTRY CLEANING SYSTEMS

Advantages and competencies An Experienced Team Brinox has more than 30 years of experience in the manufacture of equipment for the pharmaceutical, food & beverage and chemical industries. Brinox Cleaning Systems develops and manufactures systems and complete automated solutions for the cleaning of equipment from various pharmaceutical processes and applications. Based on cgmp, FDA and GAMP requirements and recommendations, Brinox maintains its own development department and a state-of-the-art manufacturing plant for washing machines and systems. BCS provides efficient and validated cleaning processes using washing, drying and cooling procedures. The cleaning of IBC containers, other washing items, and the washing system itself, is ensured using efficient water spraying, the use of various cleaning agents, proper temperatures and optimum durations for each step of the washing programmes. Brinox Cleaning Systems boast high-quality manufacturing, state-of-the-art development solutions, optimum use of water, detergents and energy media, short cleaning programmes, and simple operation via a Touchscreen HMI. Customer wishes and requirements are always taken well into account in the manufacture of BCSs. A modern control system and a dedicated SW give the user an array of options to create their own cleaning programmes, which are validated together with the client. After installation, the BCS system is thoroughly qualified, which ensures consistent quality and repeatability of processes. Brinox develops, produces and tests custom-made racks for various washing items produced by Brinox and for other producers as well. A connection between BCS systems and the customer s IT system ensures effective supervision, monitoring and archiving of all cleaning procedures and report parameters. Complete after-sales activities and servicing ensures high customer satisfaction. BCS - Brinox Cleaning Systems is the label for a family of washing machines of several sizes, and automated cleaning systems for: intermediate bulk containers (IBC) of all forms and sizes, stainless steel barrels, vessels of various sizes, aluminium transport pallets, various components for tableting, capsule-filling and other manufacturing machines and devices in pharmaceutical plants, tools and instruments used in weighing, packaging and in filling plants, development labs and similar, IBCs with integrated passive SBV flaps.

BWS 707 BWS 910 BWS 912 For cleaning of different parts of tableting-tools, capsuling and filling lines, bottles, instruments, punches and dies, stainless steel barrels up to 200 l, plastic vessels, large machine parts, funnels and flexible hoses. Versions of washers BWS 1018 BWS 1318 BWS 1322 BWS 1622 We provide the following versions for IBC cleaning, stainless steel barrels, boxes, AL pallets, large parts and more: single-chamber machines of different chamber sizes machines with one or two doors machines built into the pit of approx. 700 mm machines with additional buffer tanks to save or prepare water solutions dual- or multi-chamber machines with different chamber sizes automated transport for machine loading/unloading solutions for automatic opening of covers, flaps and SBV valves single-chamber machine with single or double sliding doors electric, steam or combined media heating technical room can be placed on the left or right side BWS 707 can be designed with extended chamber heights.

Cleaning Systems MATERIALS & COMPONENTS Material of the chamber AISI 316L (1.4404 ) mirror polished Material of the construction and covers AISI 304 (1.4301) Roughness of the surface Ra 0,8 µm Welds in chamber seam polished Ra 0,8 µm Chamber and tank with round corners, slope of flat surfaces, pipe connections and pipelines min. 2% Seals and non-metallic materials in contact with washing media with FDA conformity Chamber and pipe are insulated RACKS FOR WASHING ITEMS The use of racks is very important for the efficient cleaning of all BWS parts, as they ensure the correct and stable placement of all wash items. Based on our long experience and our flexibility in the development and production process we are able to manufacture racks for washers from other manufacturers, within a very short period of time. Development and manufacturing process of washing racks: scanning of all wash items at the customer s site, creation of LWI (List of Wash Items), creation of a 3D presentation of loading of all wash items, customer s approval of the rack, construction and manufacture of the rack, riboflavin test at the customer s site, passivation, electro polishing, quality control, documentation, delivery. SOLUTIONS FOR PHARMACEUTICAL APPLICATIONS Brinox follows FDA, cgmp and GAMP guidelines as the standard in the development of machines in the process of evaluating the technological concepts of the pharmaceutical technology and equipment.

PIPELINES Pharma pump, fully drainable, max. pressure 5 bar, material AISI 316L, roughness Ra < 0,8 µm, with additional draining valve TC pipe connections Water heating with double-walled steam heat exchanger, material AiSi 316 L Pipe dimension according to DIN EN 10357 (former DIN 11850) series A-CC, Ra <0,8µm, welds unpolished Design of pipelines Free of dead legs Purging of the installation with compressed air Pipeline passivation DOSING Dosing of detergent locally from a vessel with level control Dosing of detergent directly from the loop on the building side Measuring the amount of detergent using a flow meter Detergent concentration measurement using a conductivity probe Connection for easy calibration of the dosing system CONDUCTIVITY MEASUREMENT OF FINAL RINSE WATER Conductivity probe inside the washing chamber Conductivity probe in the circulation loop Conductivity probe in a separate drain DOOR & BIOSEAL Double horizontal sliding glass door Door movement protected with safety edge FDA-certified inflatable seal with pressure control WASHING OR RINSING NOZZLE SYSTEM Spraying with rotating nozzles or rotors on walls, ceiling and bottom of the chamber allows cleaning of the container exterior and parts on the rack. Internal spraying of IBCs performed by a 360 rotating nozzle, which moves vertically in the IBC while spraying. Movement and rotation is controlled and alarmed. All parts placed in the custom-made rack are sprayed with its own nozzle system. The rack has a flange connection, which automatically connects to the connection inside the chamber, allowing the cleaning media to flow through the rack nozzle system.

WASHING PROGRAMMES Washing programmes are individually created by the user using the TP 1500 screen by defining and adjusting parameters such as: washing temperature, time, spraying pressure, detergent type and concentration. Programme steps: Pre-washing Purging Washing I,II,III (1-10) Purging Rinsing I,II,III (1-10) Purging Drying Cooling DRYING & COOLING PROCESS CONTROL AND DOCUMENTATION Max. drying temperature 120 C, air is heated using a steam or electric heater Possibility to integrate a cooler to cool the air faster and with it the washing items to approx. 50 C before exiting the machine Version with pre-filtration, fan, heater, Hepa filter H13 or H14 (EN 1822:2009) Connections to measure the DEHS integrity of the HEPA filter. The washer process control system is based on an open SCADA/PLC platform using GE ifix SCADA and Siemens S7 PLC and is designed according to current standards and recommendations: GAMP5 project is adopted as a general guide to computer system lifecycle approach; Control system is designed according to FDA 21 CFR part 11 requirements providing secured evidence of the process run for regulatory authorities (local SQL Express database is used for data storage); A widely accepted ISA S88.01 standard is used for batch process modelling and application development to achieve a high level of flexibility. The automation system provides: OPERATION & CONTROL The main electrical cabinet is located in the service area of the machine The cabinets with IO modules ET 200 are located in various parts of the machine Control for the machine is provided by a Siemens series S7-300 PLC controller Using Ethernet, the control system can be connected to the central archiving and data processing system in compliance with FDA 21 CFR Part 11 The Touchscreen TP 1500 Comfort display on the entry side and TP 700 on the exit side allow for simple operation and display of important information SCADA system is optional. Advanced SCADA visualization and manual equipment manipulation: Every controlled valve/motor can be manually controlled from SCADA. For testing purposes and in cases of production problems sensor values can also be forced. The following process values are monitored and controlled: Temperature is measured with Pt100, Class A sensors Pressure at spray inlets Quantity of detergent is controlled Conductivity of final rinse Rotation speed of the rotors is monitored and alarmed HEPA filter pressure drop Flexible, S88.01 recipe system provides high recipe flexibility resulting in optimized washing sequences for many different inserts or wash items. Using an SQL database enables a practically unlimited number of recipes. Recipes are subjected to a predefined approval process using E-signatures. Electronic batch reporting and Audit-trail system provides complete production reports in electronic or printed form. 21CFR11 support with access control based on Windows security. SCADA screens in English/local language. Interface to other systems: PW water system MES system: automated recipe selection based on product and automated washing report integration in overall MES EBR. HVAC system

MES CONTROLLED WASHING DOCUMENTATION Qualification documents Qualification plan IQ-documentation OQ-documentation FAT/SAT Report on qualifications Our washing machines can be connected to an MES software layer. Two kinds of interface are supported OPC or database interface. Recipe selection is made by a MES system based on the barcode on the washing object (the barcode is scanned automatically or manually at the washer). Fully automated workflow and cleaning EBR integrity is achieved this way, eliminating possible operator errors. Material and welding documentation Certificates 2.1, 2.2 or 3.1 User documentation Machine user manual Machine maintenance manual List of spare / wear parts and recommended spare parts FDA conformity certificates for non-metal parts Welding documentation for the entire machine Technical documentation of the machine: P&ID diagram Electrical diagram Machine installation Warranty certificate and compliance statement Figure 1. Software architecture of control system

TECHNICAL DATA MODEL Usable chamber dimensions W x H x D [mm] Chamber volume [m 3 ] Outer dimensions W x H x D [m] Loading height [mm] Machine in pit / Loading height [m] Number of doors Door opening Tank volume [L] CONNECTIONS Cold water Warm water PW/WFI water Electricity Steam Condensate Drain water Air outlet BWS 707 700 x 700 x 800 0,39 1,5 x 2,3 x 1,1 - vertically 50 DN20 2-3 bar DN20 2-3 bar DN20 2-3 bar - - DN65 DN100 BWS 910 900 x 1000 x 900 0,81 2,4 x 2,2 x 1,4-60 DN40 3 bar 143 C DN25 DN65 DN150 BWS 912 900 x 1200 x 1200 1,30 2,4 x 2,5 x 1,7-60 DN40 3 bar 143 C DN25 DN65 DN150 BWS 1018 1000 x 1800 x 1600 2,88 3,05 x 3,1 x 2,36-700/0 120 DN50 3 bar 143 C DN32 DN80 DN200 BWS 1318 1300 x 1800 x 1600 3,74 3,35 x 3,1 x 2,36-700/0 120 DN50 3 bar 143 C DN32 DN80 DN200 BWS 1322 1300 x 2200 x 1600 4,58 3,35 x 3,4 x 2,36-700/0 140 DN50 3 bar 143 C DN32 DN100 DN200 BWS 1622 1600 x 2200 x 2000 7,04 3,95 x 3,4 x 2,76-700/0 180 DN65 3 bar 143 C DN40 DN100 DN250