Solution scenario Validated Pharmaceutical plant Overall enterprise integration in a validated environment

Issues: Enterprise Integration and validation Industry: Pharmaceuticals Overall enterprise integration SAP integration for scheduling and master recipes Enterprise connection to diverse systems including: HVAC, mixing, maintenance management product routing and water systems Total plant pharmaceutical industry validation When the new pharmaceutical plant was planned, several key aspects were considered regarding plant automation: Total plant integration, including asset management, production planning, batch administration and control, product delivery, maintenance management and plant documentation; Whole plant validation, including systems validation and plant procedures, documented according to strict pharmaceutical industry validation rules; (additional requirements, on next notes page) This large pharmaceutical manufacturing facility produces over 3 billion tablets annually

Additional requirements Regulatory compliance in the design and deployment of products and systems from the plant floor to the ERP level Process, raw material, and product tracking and control High level of operator interaction Automated sampling data entry In addition to total plant integration and whole plant validation, other requirements included: System reliability, including means for individual systems to work in a “non-integrated” mode during network problems, and disaster recovery procedures in the event of total destruction of any server. Design and deployment of different products to the plant floor at ERP level, by creation or revision of master recipes with change control tracking, and providing that actual production recipes. The production data can not be altered at any time before, during and after production; Process, raw materials and product tracking and control, including batch documentation according to country and international regulations; Great level of operator interaction, including several manual tasks and on-the-fly comments, providing every operator transaction with electronic signatures; Automation of sampling data entry whenever possible, including type of tests and checking of allowable limits according to the master recipe;

ABB Solution: Enterprise Integration System integration services were provided by ABB Inform IT Enterprise Historian selected as the heart of the ERP/MES/Plant Floor for production related activities Planning functions are logically and physically separated from production. In the event of a network failure, the MES system continues production for days based upon previously downloaded SAP production orders

ABB Solution: Enterprise Integration SAP system selected as the basis for recipe development, production planning and material movement and permanent batch records ABB handled distribution and synchronization of recipes across multiple, independently controlled process areas ABB is responsible for the electronic batch record keeping Data is collected into the Enterprise Historian ABB application consolidates the batch record and forwards it to SAP

ABB Solution: architectural view Building control system Product Routing Mixing system SAP Production scheduling, orders, final batch records supervision & accounting Process management Barcode system Production lines ABB Solution: architectural view Enterprise Historian To achieve a best-in-class solution, several different systems from several providers were integrated in a plantwide network. Some of the production lines were existing lines in use in other facilities and others were brand new . ABB’s Inform IT Enterprise Historian was selected as the heart of the ERP/MES/Plant Floor integration for production-related and batch-related activities (including ERP recording); the SAP system was selected as the base block for recipe development, production planning and material movement. All the terminals and interfaces are connected to one TCP/IP network, except for the PLCs that could not be connected to TCP/IP. The Building Control System is connected via Modbus in order to integrate all pharmaceutical relevant values belonging to the auxiliary systems into the electronic batch record. Line# 1 PLC has a custom interface and the other line PLCs use a Profibus L2 interface. The Mixing System interface is Siemens H1, that uses ethernet technologyand has been connected to the plant network. Throughout this system, planning functions are logically and physically separated (even in different buildings). In the event of a network failure, the MES system can continue producing for a few days using information that was previously downloaded.

ABB Solution: Enterprise Integration ERP system interface via SAP certified software (Verano Enterprise Link) Production orders Quality data Batch records (schedule) Material short-term tracking Operator interface Automation system interface Peripherals interface Maintenance system (CMMS) interface Historical process recording Uniqueness of the data sources is insured, simplifying change control tracking via SAP and preserving data access security. Recipes are sent to the control system after they are approved by SAP, a few days in advance of actual production. The MES-ERP interface is a SAP certified software (Verano Enterprise Link), which ensures data integrity, and preserves against data loss or duplication. All GMP relevant data captured by the system is included in the electronic batch record and sent to SAP for archiving purposes. These records can be viewed online at any time using a standard web browser over the plant network. At the end of the batch it is automatically printed and saved in PDF format. Throughout the entire process relevant data can be entered at only one place. The recipe planner can decide at which terminals the recipe can be seen and from which terminal data can be entered at each phase. The system provides many different user levels, which have authority for different tasks, at different operation points, thus permitting a complete control over who, when and where data can be entered. All information entered by operators or maintenance personnel is recorded in the electronic batch record or in the plant logbook (maintenance data), with timestamp and electronic signature. For maintenance purposes, there is a database application for viewing historical logbook entries. This allows data to be filtered by equipment, date, process line, etc. More sophisticated reports can be done at the Mantec CMMS, which receives all logbook, alarm and event data through a custom interface. Master recipe changes are handled by SAP; implementation changes are handled and recorded using a Lotus Notes database. ABB project documentation is served by the ABB EH, using the Netscape Fasttrack Web Server; a full-system documentation software project is being implemented. These features allow for complete elimination of paper (except printed and hand-signed EBR, as required by the Argentina authorities), even for maintenance tracking. The following functions are provided by the ABB MES system: I. ERP system Interface – The interface between ERP and MES provides a configurable mechanism for the transfer of information between the two environments. Recipe data (including planned date) is sent from SAP to the MES. During recipe execution material consumption and production, quality samples and other GMP relevant data is sent to the SAP system. II. Material short-term tracking – When SAP accounts for material validity before sending them to the plant floor, some raw materials could be expired. The MES system checks that only valid materials are used for in-process materials which are to be packaged. If a mixture is not approved or its validity date expires, the system will not allow it to be packaged. III. Operator Interface – Specific transactions must be initiated by the operator (confirming cleaning condition, visual checks, etc.). Data entry is accomplished with an interface that is configurable during recipe development and minimizes data entry, thereby decreasing human errors. Whenever possible, data is entered via barcode reading ( i.e. raw material lot and weight readings, operator signature, etc.). Operator activity is restricted and allowed only at specific times during the work order. It is then validated (authority level and signature), and time-stamped. Mistaken entries are indicated to the operator with an error reason. This allows correction and re-entry. IV. Automation systems interface – The system provides all automation systems interfaces. Data is retrieved from various vendors’ equipment during production and linked to the proper work order where relevant. Real-time data is available operator screens for monitoring of operating conditions. Data is sent to specific systems to properly trigger recipe related tasks (i.e., mix recipe is sent to the mixing system when mixing needs to be done; routing data is sent to the product routing system at the beginning of each batch.) V. Peripherals interface – Additional information needed during production (i.e.: weight samples, hardness samples, visual indications, etc.) is handled by the MES system. Where needed, custom interfaces have been developed through the relational database. For example, a wall sign system is required to show the current lot number, validity date and product description. This is done using a custom driver which retrieves data from the MES database. VI. Maintenance system interface – Logbook information is sent to a Mantec CMMS for maintenance personnel usage. Working hours of rotating equipment, trends, alarms and events are used by this system to plan schedule maintenance functions. VII. Historical Recording and Electronic Batch Records – Detailed information related to production operations, sampling, material usage, process conditions, etc., is captured and stored in one or more of the following archives: Electronic batch record (GMP relevant and other recipe-related data), Logbook (maintenance data, alarms and events) and History Trends (continuous data as temperatures, pressures, etc.). Data is stored in a relational database and can be extracted on demand at any moment.

Industrial IT solution: validation and security Data source uniqueness is preserved Data can only be entered at one place All operator and maintenance personnel entries recorded (by an electronic batch recording system) Project documentation is available at the Enterprise Historian served up by Netscape Fasttrack web server. Goal is to become paperless.